---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22229'
abstract:
- lang: eng
text: Hippocampal CA3 pyramidal neurons (PNs) form the largest autoassociative network
in the mammalian brain. Whether CA3–CA3 recurrent connectivity is genetically
preconfigured or environmentally shaped during ongoing memory storage is currently
unknown. To address this question, we performed multicellular patch-clamp-based
circuit mapping of up to eight CA3 PNs in the mouse hippocampus at multiple postnatal
time points (P7–8, P18–25, and P45–50). Here, we show that the hippocampal CA3
network undergoes a developmental transformation from local, dense, and random
connectivity to a distributed, sparse, and structured configuration. Thus, sparse
and structured connectivity may emerge via experience-dependent mechanisms. In
parallel, the strength of single synapses is downregulated; single synaptic events
are sufficient to trigger postsynaptic spiking early in development, whereas spatial
summation of several inputs is required at later time points. Biologically inspired
models of memory storage by Hebbian synaptic plasticity and retrieval via pattern
completion suggest that developmental changes improve specific aspects of memory
storage and retrieval. Our results imply a developmental transformation of the
neuronal code and the memory functions in the hippocampal CA3 network.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: M-Shop
- _id: ScienComp
acknowledgement: 'We thank Jose Guzman, Simon Hippenmeyer, and Tim Vogels for critically
reading the manuscript, Jozsef Csicsvari for useful discussions, Florian Marr for
technical assistance, and Eleftheria Kralli-Beller for manuscript editing. This
research was supported by the Scientific Services Units (SSUs) of ISTA: the preclinical
facility (PCF) provided housing and breeding of the animals, the imaging and optics
facility (IOF) offered technical training and state of the art equipment, the Miba
machine shop contributed to the construction and maintenance of multicellular recording
setups, and the scientific computing unit helped with the large-scale simulations.
The project received funding from the European Union’s Horizon 2020 research and
innovation programme (ERC Advanced Grants No 692692 GIANTSYN and 101199096 CA3-SYNGRAM
to P.J.; Marie Skłodowska-Curie Grant 754411 to V.V.B.; Marie Skłodowska-Curie Grant
101026635 to J.F.W.), the Fond zur Förderung der Wissenschaftlichen Forschung (P
36232-B, PAT4178023, and 10.55776/CoE16 to P.J.), and the Nomis Foundation (fellowship
to A.N.-O.). V.V.B. received funding from a CONACyT fellowship (289638).'
article_number: '5540'
article_processing_charge: Yes
article_type: original
author:
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Andrea C
full_name: Navas Olivé, Andrea C
id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
last_name: Navas Olivé
orcid: 0000-0002-9280-8597
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. Developmental
emergence of sparse and structured synaptic connectivity in the hippocampal CA3
memory circuit. Nature Communications. 2026;17. doi:10.1038/s41467-026-71914-x
apa: Vargas Barroso, V. M., Watson, J., Navas Olivé, A. C., Schlögl, A., & Jonas,
P. M. (2026). Developmental emergence of sparse and structured synaptic connectivity
in the hippocampal CA3 memory circuit. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-026-71914-x
chicago: Vargas Barroso, Victor M, Jake Watson, Andrea C Navas Olivé, Alois Schlögl,
and Peter M Jonas. “Developmental Emergence of Sparse and Structured Synaptic
Connectivity in the Hippocampal CA3 Memory Circuit.” Nature Communications.
Springer Nature, 2026. https://doi.org/10.1038/s41467-026-71914-x.
ieee: V. M. Vargas Barroso, J. Watson, A. C. Navas Olivé, A. Schlögl, and P. M.
Jonas, “Developmental emergence of sparse and structured synaptic connectivity
in the hippocampal CA3 memory circuit,” Nature Communications, vol. 17.
Springer Nature, 2026.
ista: Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. 2026. Developmental
emergence of sparse and structured synaptic connectivity in the hippocampal CA3
memory circuit. Nature Communications. 17, 5540.
mla: Vargas Barroso, Victor M., et al. “Developmental Emergence of Sparse and Structured
Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” Nature Communications,
vol. 17, 5540, Springer Nature, 2026, doi:10.1038/s41467-026-71914-x.
short: V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas,
Nature Communications 17 (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: Source data are provided with this paper. Additional original
data are available from the corresponding author upon request. Code is available
from https://doi.org/10.15479/AT-ISTA-21442 under the link https://research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz
date_created: 2026-06-30T13:05:52Z
date_published: 2026-06-23T00:00:00Z
date_updated: 2026-07-01T06:47:49Z
day: '23'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1038/s41467-026-71914-x
ec_funded: 1
external_id:
pmid:
- '42014695'
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oa: 1
oa_version: Published Version
pmid: 1
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call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: e62b56fe-ab3c-11f0-94c7-d181dd352b3b
grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
grant_number: PAT 4178023
name: Synaptic networks of human brain
- _id: 26366136-B435-11E9-9278-68D0E5697425
name: Reglas de Conectividad funcional en el hipocampo
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
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supplementarymaterial: yes
title: Developmental emergence of sparse and structured synaptic connectivity in the
hippocampal CA3 memory circuit
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2026'
...
---
OA_type: closed access
_id: '22305'
abstract:
- lang: eng
text: Active dendrites enrich the repertoire of single-neuron computations. Whereas
a lot is known about the function of dendrites in vitro, information about their
in vivo properties is limited. A new study1 uses advanced imaging to study hippocampal
CA1 pyramidal neuron dendrites in head-fixed, awake animals.
article_processing_charge: No
article_type: letter_note
author:
- first_name: Subhodeep
full_name: Bhattacharya, Subhodeep
id: 45f74010-66f6-11f0-a7d4-c441fa3685ff
last_name: Bhattacharya
orcid: 0009-0009-0334-9068
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Bhattacharya S, Jonas PM. Mission impossible? Quantitative analysis of dendritic
computations in vivo. Neuron. 2026;114(10):1706-1708. doi:10.1016/j.neuron.2026.04.002
apa: Bhattacharya, S., & Jonas, P. M. (2026). Mission impossible? Quantitative
analysis of dendritic computations in vivo. Neuron. Cell Press. https://doi.org/10.1016/j.neuron.2026.04.002
chicago: Bhattacharya, Subhodeep, and Peter M Jonas. “Mission Impossible? Quantitative
Analysis of Dendritic Computations in Vivo.” Neuron. Cell Press, 2026.
https://doi.org/10.1016/j.neuron.2026.04.002.
ieee: S. Bhattacharya and P. M. Jonas, “Mission impossible? Quantitative analysis
of dendritic computations in vivo,” Neuron, vol. 114, no. 10. Cell Press,
pp. 1706–1708, 2026.
ista: Bhattacharya S, Jonas PM. 2026. Mission impossible? Quantitative analysis
of dendritic computations in vivo. Neuron. 114(10), 1706–1708.
mla: Bhattacharya, Subhodeep, and Peter M. Jonas. “Mission Impossible? Quantitative
Analysis of Dendritic Computations in Vivo.” Neuron, vol. 114, no. 10,
Cell Press, 2026, pp. 1706–08, doi:10.1016/j.neuron.2026.04.002.
short: S. Bhattacharya, P.M. Jonas, Neuron 114 (2026) 1706–1708.
corr_author: '1'
das_tickbox: '0'
date_created: 2026-07-13T10:51:27Z
date_published: 2026-05-20T00:00:00Z
date_updated: 2026-10-20T09:00:56Z
day: '20'
department:
- _id: PeJo
doi: 10.1016/j.neuron.2026.04.002
external_id:
pmid:
- '42161246'
fulldoi: https://doi.org/10.1016/j.neuron.2026.04.002
intvolume: ' 114'
issue: '10'
language:
- iso: eng
month: '05'
oa_version: None
page: 1706-1708
pmid: 1
publication: Neuron
publication_identifier:
issn:
- 0896-6273
publication_status: published
publisher: Cell Press
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Mission impossible? Quantitative analysis of dendritic computations in vivo
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 114
year: '2026'
...
---
OA_place: publisher
OA_type: hybrid
_id: '18879'
abstract:
- lang: eng
text: 'Our brain has remarkable computational power, generating sophisticated behaviors,
storing memories over an individual’s lifetime, and producing higher cognitive
functions. However, little of our neuroscience knowledge covers the human brain.
Is this organ truly unique, or is it a scaled version of the extensively studied
rodent brain? Combining multicellular patch-clamp recording with expansion-based
superresolution microscopy and full-scale modeling, we determined the cellular
and microcircuit properties of the human hippocampal CA3 region, a fundamental
circuit for memory storage. In contrast to neocortical networks, human hippocampal
CA3 displayed sparse connectivity, providing a circuit architecture that maximizes
associational power. Human synapses showed unique reliability, high precision,
and long integration times, exhibiting both species- and circuit-specific properties.
Together with expanded neuronal numbers, these circuit characteristics greatly
enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit
properties of the human hippocampus and begin to unravel the inner workings of
our most complex organ. '
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: ScienComp
acknowledgement: We thank Florian Marr for excellent technical assistance, Christina
Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor
Asenov for development of the transportation box for human brain tissue, Tim Vogels
for guidance on simulations, Marcus Huber for mathematical advice, Walter Kaufmann
for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript
editing. This research was supported by the Scientific Services Units (SSUs) of
ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and
Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop,
and Scientific Computing. We are particularly grateful to the patient donors for
their support of this project and also acknowledge the excellent support of the
Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger
and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division
of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha
Feucht, and Ekaterina Pataraia for their clinical care of the patients included
in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample
donors for their support of this research. The project received funding from the
European Research Council (ERC) under the European Union’s Horizon 2020 research
and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie
Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
(FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian
Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship
(to A.N.-O.).
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Rebecca
full_name: Morse, Rebecca
id: ceb89ae7-dc8d-11ea-abe3-da3301d0eab4
last_name: Morse
- first_name: Andrea C
full_name: Navas Olivé, Andrea C
id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
last_name: Navas Olivé
orcid: 0000-0002-9280-8597
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Matthias
full_name: Tomschik, Matthias
last_name: Tomschik
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Watson J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific
functional connectivity rules for efficient associative memory. Cell. 2025;188(2):501-514.e18.
doi:10.1016/j.cell.2024.11.022
apa: Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli,
M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. Cell. Cell Press.
https://doi.org/10.1016/j.cell.2024.11.022
chicago: Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé,
Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M
Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for
Efficient Associative Memory.” Cell. Cell Press, 2025. https://doi.org/10.1016/j.cell.2024.11.022.
ieee: J. Watson et al., “Human hippocampal CA3 uses specific functional connectivity
rules for efficient associative memory,” Cell, vol. 188, no. 2. Cell Press,
p. 501–514.e18, 2025.
ista: Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG,
Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.
mla: Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
Rules for Efficient Associative Memory.” Cell, vol. 188, no. 2, Cell Press,
2025, p. 501–514.e18, doi:10.1016/j.cell.2024.11.022.
short: J. Watson, V.M. Vargas Barroso, R. Morse, A.C. Navas Olivé, M. Tavakoli,
J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, Cell 188 (2025) 501–514.e18.
corr_author: '1'
date_created: 2025-01-26T23:01:49Z
date_published: 2025-01-23T00:00:00Z
date_updated: 2026-10-20T08:20:04Z
day: '23'
ddc:
- '570'
department:
- _id: JoDa
- _id: PeJo
- _id: GradSch
doi: 10.1016/j.cell.2024.11.022
ec_funded: 1
external_id:
isi:
- '001408395600001'
pmid:
- '39667938'
file:
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checksum: d5a818edc32d249cdf75e1bb5b70a4b7
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creator: dernst
date_created: 2025-01-27T08:46:33Z
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issue: '2'
language:
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month: '01'
oa: 1
oa_version: Published Version
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project:
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call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
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call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
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grant_number: '26137'
name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
grant_number: PAT 4178023
name: Synaptic networks of human brain
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name: NOMIS Fellowship Program
publication: Cell
publication_identifier:
eissn:
- 1097-4172
issn:
- 0092-8674
publication_status: published
publisher: Cell Press
quality_controlled: '1'
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scopus_import: '1'
status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
associative memory
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
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type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 188
year: '2025'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '20099'
abstract:
- lang: eng
text: The hippocampus, critical for learning and memory, is dogmatically described
as a trisynaptic circuit where dentate gyrus granule cells (GCs), CA3 pyramidal
neurons (PNs), and CA1 PNs are serially connected. However, CA3 also forms an
autoassociative network, and its PNs have diverse morphologies, intrinsic properties,
and GC input levels. How PN subtypes compose this recurrent network is unknown.
To determine the synaptic arrangement of identified CA3 PNs, we combine multicellular
patch-clamp recording and post hoc morphological analysis in mouse hippocampal
slices. PNs can be divided into distinct “superficial” and “deep” subclasses,
the latter including previously reported “athorny” cells. Subclasses have distinct
input-output transformations and asymmetric connectivity, which is more abundant
from superficial to deep PNs, splitting CA3 locally into two parallel recurrent
networks. Coincident spontaneous inhibition occurs frequently within but not between
subclasses, implying subclass-specific inhibitory innervation. Our results suggest
two separately controlled sublayers for parallel information processing in hippocampal
CA3.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
acknowledgement: We thank Andrea Navas-Olive and Rebecca J. Morse-Mora for critically
reading an earlier version of the manuscript. We also thank Florian Marr and Christina
Altmutter for excellent technical assistance, Alois Schlögl for programming and
data-handling assistance, Todor Asenov for technical support, and Eleftheria Kralli-Beller
for manuscript editing. This research was supported by the Scientific Services Units
(SSUs) of ISTA. We are particularly grateful for assistance from the Imaging and
Optics Facility, Preclinical Facility, Lab Support Facility, and Miba Machine Shop.
The project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation program (grant agreement no.
692692 to P.J., Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635
to J.F.W., and an ISTplus Fellowship through Marie Skłodowska-Curie grant agreement
no. 754411 to V.V.-B.), the Austrian Science Fund (P 36232-B, PAT 4178023, and Cluster
of Excellence 10.55776/COE16 to P.J.), and a CONACyT fellowship (289638 to V.V.-B.)
and was supported by a non-stipendiary EMBO fellowship (ALTF 756–2020 to J.F.W.).
article_number: '116080'
article_processing_charge: Yes
article_type: original
author:
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Watson J, Vargas Barroso VM, Jonas PM. Cell-specific wiring routes information
flow through hippocampal CA3. Cell Reports. 2025;44(8). doi:10.1016/j.celrep.2025.116080
apa: Watson, J., Vargas Barroso, V. M., & Jonas, P. M. (2025). Cell-specific
wiring routes information flow through hippocampal CA3. Cell Reports. Cell
Press. https://doi.org/10.1016/j.celrep.2025.116080
chicago: Watson, Jake, Victor M Vargas Barroso, and Peter M Jonas. “Cell-Specific
Wiring Routes Information Flow through Hippocampal CA3.” Cell Reports.
Cell Press, 2025. https://doi.org/10.1016/j.celrep.2025.116080.
ieee: J. Watson, V. M. Vargas Barroso, and P. M. Jonas, “Cell-specific wiring routes
information flow through hippocampal CA3,” Cell Reports, vol. 44, no. 8.
Cell Press, 2025.
ista: Watson J, Vargas Barroso VM, Jonas PM. 2025. Cell-specific wiring routes information
flow through hippocampal CA3. Cell Reports. 44(8), 116080.
mla: Watson, Jake, et al. “Cell-Specific Wiring Routes Information Flow through
Hippocampal CA3.” Cell Reports, vol. 44, no. 8, 116080, Cell Press, 2025,
doi:10.1016/j.celrep.2025.116080.
short: J. Watson, V.M. Vargas Barroso, P.M. Jonas, Cell Reports 44 (2025).
corr_author: '1'
date_created: 2025-08-03T22:01:30Z
date_published: 2025-08-01T00:00:00Z
date_updated: 2026-10-20T08:55:57Z
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intvolume: ' 44'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: 0a6c8641-b036-11f1-bacf-e4eec62b5bb4
grant_number: COE16
name: Neuronal circuits in health and disease (Jonas)
publication: Cell Reports
publication_identifier:
eissn:
- 2211-1247
issn:
- 2639-1856
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Cell-specific wiring routes information flow through hippocampal CA3
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 44
year: '2025'
...
---
APC_amount: 6248,82 EUR
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OA_place: publisher
OA_type: gold
_id: '18603'
abstract:
- lang: eng
text: It is widely believed that information storage in neuronal circuits involves
nanoscopic structural changes at synapses, resulting in the formation of synaptic
engrams. However, direct evidence for this hypothesis is lacking. To test this
conjecture, we combined chemical potentiation, functional analysis by paired pre-postsynaptic
recordings, and structural analysis by electron microscopy (EM) and freeze-fracture
replica labeling (FRL) at the rodent hippocampal mossy fiber synapse, a key synapse
in the trisynaptic circuit of the hippocampus. Biophysical analysis of synaptic
transmission revealed that forskolin-induced chemical potentiation increased the
readily releasable vesicle pool size and vesicular release probability by 146%
and 49%, respectively. Structural analysis of mossy fiber synapses by EM and FRL
demonstrated an increase in the number of vesicles close to the plasma membrane
and the number of clusters of the priming protein Munc13-1, indicating an increase
in the number of both docked and primed vesicles. Furthermore, FRL analysis revealed
a significant reduction of the distance between Munc13-1 and CaV2.1 Ca2+ channels,
suggesting reconfiguration of the channel-vesicle coupling nanotopography. Our
results indicate that presynaptic plasticity is associated with structural reorganization
of active zones. We propose that changes in potential nanoscopic organization
at synaptic vesicle release sites may be correlates of learning and memory at
a plastic central synapse.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
acknowledgement: "We thank Carolina Borges-Merjane, Jing-Jing Chen, Katharina Lichter,
and Samuel Young for critically reading the manuscript; the Electron Microscopy
Facility of ISTA, in particular Vanessa Zheden, for extensive support, advice, and
experimental assistance; the Preclinical Facility of ISTA, in particular Victoria
Wimmer and Michael Schunn, for experimental assistance; Florian Marr and Christina
Altmutter for technical support; Alois Schlögl for help with analysis; and Eleftheria
Kralli-Beller for manuscript editing. We also thank Cordelia Imig for providing
Munc13-1cKO-Munc13-2/3(−/−) mutant mice. Part of the work has been published in
O.K.’s thesis in partial fulfillment of the requirements for the degree of Doctor
of Philosophy.\r\nThis project received funding from the European Research Council
and European Union’s Horizon 2020 research and innovation programme (ERC 692692
to P.J.; https://cordis.europa.eu/project/id/692692/de) and from the Fond zur Förderung
der Wissenschaftlichen Forschung (Z312-B27 Wittgenstein award to P.J., https://www.fwf.ac.at/en/funding/portfolio/projects/fwf-wittgenstein-award;
W1205-B09 and P36232-B to P.J., https://www.fwf.ac.at/en/funding; I6166-B to R.S.;
https://www.fwf.ac.at/en/funding). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the manuscript."
article_number: e3002879
article_processing_charge: Yes
article_type: original
author:
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
orcid: 0000-0003-2344-1039
- first_name: Yuji
full_name: Okamoto, Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Nils
full_name: Brose, Nils
last_name: Brose
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. Presynaptic cAMP-PKA-mediated
potentiation induces reconfiguration of synaptic vesicle pools and channel-vesicle
coupling at hippocampal mossy fiber boutons. PLoS Biology. 2024;22(11).
doi:10.1371/journal.pbio.3002879
apa: Kim, O., Okamoto, Y., Kaufmann, W., Brose, N., Shigemoto, R., & Jonas,
P. M. (2024). Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration
of synaptic vesicle pools and channel-vesicle coupling at hippocampal mossy fiber
boutons. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3002879
chicago: Kim, Olena, Yuji Okamoto, Walter Kaufmann, Nils Brose, Ryuichi Shigemoto,
and Peter M Jonas. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons.” PLoS Biology. Public Library of Science, 2024. https://doi.org/10.1371/journal.pbio.3002879.
ieee: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, and P. M. Jonas,
“Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic
vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons,”
PLoS Biology, vol. 22, no. 11. Public Library of Science, 2024.
ista: Kim O, Okamoto Y, Kaufmann W, Brose N, Shigemoto R, Jonas PM. 2024. Presynaptic
cAMP-PKA-mediated potentiation induces reconfiguration of synaptic vesicle pools
and channel-vesicle coupling at hippocampal mossy fiber boutons. PLoS Biology.
22(11), e3002879.
mla: Kim, Olena, et al. “Presynaptic CAMP-PKA-Mediated Potentiation Induces Reconfiguration
of Synaptic Vesicle Pools and Channel-Vesicle Coupling at Hippocampal Mossy Fiber
Boutons.” PLoS Biology, vol. 22, no. 11, e3002879, Public Library of Science,
2024, doi:10.1371/journal.pbio.3002879.
short: O. Kim, Y. Okamoto, W. Kaufmann, N. Brose, R. Shigemoto, P.M. Jonas, PLoS
Biology 22 (2024).
corr_author: '1'
date_created: 2024-12-01T23:01:54Z
date_published: 2024-11-18T00:00:00Z
date_updated: 2026-04-16T12:20:34Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1371/journal.pbio.3002879
ec_funded: 1
external_id:
isi:
- '001358568700003'
pmid:
- '39556620'
file:
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checksum: 7de2dcb50deb65dde05c80082bb85a82
content_type: application/pdf
creator: dernst
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file_date_updated: 2024-12-03T08:56:53Z
fulldoi: https://doi.org/10.1371/journal.pbio.3002879
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intvolume: ' 22'
isi: 1
issue: '11'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
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call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
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grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
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grant_number: I06166
name: Structural & functional basis of presynaptic plasticity
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call_identifier: FWF
grant_number: W01205
name: Zellkommunikation in Gesundheit und Krankheit
- _id: 3AC91DDA-15DF-11EA-824D-93A3E7B544D1
call_identifier: FWF
name: FWF Open Access Fund
publication: PLoS Biology
publication_identifier:
eissn:
- 1545-7885
issn:
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publisher: Public Library of Science
quality_controlled: '1'
related_material:
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relation: research_data
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status: public
title: Presynaptic cAMP-PKA-mediated potentiation induces reconfiguration of synaptic
vesicle pools and channel-vesicle coupling at hippocampal mossy fiber boutons
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 22
year: '2024'
...
---
_id: '15117'
abstract:
- lang: eng
text: 'The hippocampal mossy fiber synapse, formed between axons of dentate gyrus
granule cells and dendrites of CA3 pyramidal neurons, is a key synapse in the
trisynaptic circuitry of the hippocampus. Because of its comparatively large size,
this synapse is accessible to direct presynaptic recording, allowing a rigorous
investigation of the biophysical mechanisms of synaptic transmission and plasticity.
Furthermore, because of its placement in the very center of the hippocampal memory
circuit, this synapse seems to be critically involved in several higher network
functions, such as learning, memory, pattern separation, and pattern completion.
Recent work based on new technologies in both nanoanatomy and nanophysiology,
including presynaptic patch-clamp recording, paired recording, super-resolution
light microscopy, and freeze-fracture and “flash-and-freeze” electron microscopy,
has provided new insights into the structure, biophysics, and network function
of this intriguing synapse. This brings us one step closer to answering a fundamental
question in neuroscience: how basic synaptic properties shape higher network computations.'
acknowledgement: "We thank previous students, postdocs, and collaborators, particularly
J. Geiger, and (in alphabetical order) H. Alle, J. Bischofberger, C. Borges-Merjane,
D. Engel, M. Frotscher, S. Hallermann, M. Heckmann, S. Jamrichova, O. Kim, L. Li,
K. Lichter, P. Lin, J. Lübke, Y. Okamoto, C. Pawlu, C. Schmidt-Hieber, N. Spruston,
and N. Vyleta for their outstanding experimental contributions. We also thank P.
Castillo, J. Geiger, T. Sakaba, S. Siegert, T. Vogels, and J. Watson for critically
reading the manuscript, E. Kralli-Beller for text editing, and J. Malikovic and
L. Slomianka for useful discussions. We apologize that, due to space constraints,
not all relevant papers could be cited.\r\nThis project was supported by the European
Research Council (ERC) under the European Union’s Horizon 2020 research and innovation
program (grant agreement 692692, AdG “GIANTSYN”) and the Fonds zur Förderung der
Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein Award; P 36232-B, stand-alone
grant), both to P.J."
article_processing_charge: No
article_type: review
author:
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vandael DH, Jonas PM. Structure, biophysics, and circuit function of a “giant”
cortical presynaptic terminal. Science. 2024;383(6687):eadg6757. doi:10.1126/science.adg6757
apa: Vandael, D. H., & Jonas, P. M. (2024). Structure, biophysics, and circuit
function of a “giant” cortical presynaptic terminal. Science. AAAS. https://doi.org/10.1126/science.adg6757
chicago: Vandael, David H, and Peter M Jonas. “Structure, Biophysics, and Circuit
Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science. AAAS, 2024.
https://doi.org/10.1126/science.adg6757.
ieee: D. H. Vandael and P. M. Jonas, “Structure, biophysics, and circuit function
of a ‘giant’ cortical presynaptic terminal,” Science, vol. 383, no. 6687.
AAAS, p. eadg6757, 2024.
ista: Vandael DH, Jonas PM. 2024. Structure, biophysics, and circuit function of
a ‘giant’ cortical presynaptic terminal. Science. 383(6687), eadg6757.
mla: Vandael, David H., and Peter M. Jonas. “Structure, Biophysics, and Circuit
Function of a ‘Giant’ Cortical Presynaptic Terminal.” Science, vol. 383,
no. 6687, AAAS, 2024, p. eadg6757, doi:10.1126/science.adg6757.
short: D.H. Vandael, P.M. Jonas, Science 383 (2024) eadg6757.
corr_author: '1'
das_tickbox: '0'
date_created: 2024-03-17T23:00:57Z
date_published: 2024-03-08T00:00:00Z
date_updated: 2026-09-17T09:49:03Z
day: '08'
department:
- _id: PeJo
doi: 10.1126/science.adg6757
ec_funded: 1
external_id:
isi:
- '001216996700015'
pmid:
- '38452088'
fulldoi: https://doi.org/10.1126/science.adg6757
intvolume: ' 383'
isi: 1
issue: '6687'
language:
- iso: eng
month: '03'
oa_version: None
page: eadg6757
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
publication: Science
publication_identifier:
eissn:
- 1095-9203
publication_status: published
publisher: AAAS
quality_controlled: '1'
researchdata_availability: no
scopus_import: '1'
status: public
supplementarymaterial: no
title: Structure, biophysics, and circuit function of a "giant" cortical presynaptic
terminal
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 383
year: '2024'
...
---
OA_place: repository
_id: '18688'
abstract:
- lang: eng
text: The human brain has remarkable computational power. It generates sophisticated
behavioral sequences, stores engrams over an individual’s lifetime, and produces
higher cognitive functions up to the level of consciousness. However, so little
of our neuroscience knowledge covers the human brain, and it remains unknown whether
this organ is truly unique, or is a scaled version of the extensively studied
rodent brain. To address this fundamental question, we determined the cellular,
synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using
multicellular patch clamp-recording. This circuit is the largest autoassociative
network in the brain, and plays a key role in memory and higher-order computations
such as pattern separation and pattern completion. We demonstrate that human hippocampal
CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks.
Connectivity sparsifies from rodents to humans, providing a circuit architecture
that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses
showed both distinct species-specific and circuit-dependent properties, with high
reliability, unique amplitude precision, and long integration times. We also identify
differential scaling rules between hippocampal pathways from rodents to humans,
with a moderate increase in the convergence of CA3 inputs per cell, but a marked
increase in human mossy fiber innervation. Anatomically guided full-scale modeling
suggests that the human brain’s sparse connectivity, expanded neuronal number,
and reliable synaptic signaling combine to enhance the associative memory storage
capacity of CA3. Together, our results reveal unique rules of connectivity and
synaptic signaling in the human hippocampus, demonstrating the absolute necessity
of human brain research and beginning to unravel the remarkable performance of
our autoassociative memory circuits.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: PreCl
- _id: ScienComp
acknowledgement: We thank Florian Marr for excellent technical assistance, Christina
Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor
Asenov for development of the transportation box for human brain tissue, Tim Vogels
for guidance on simulations, Marcus Huber for mathematical advice, and Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA, and we are particularly grateful for assistance from
Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Life
Science Facility, Miba Machine Shop, and Scientific Computing. We also acknowledge
the excellent support of the Medical University of Vienna Department of Neurosurgery
staff, Romana Hoeftberger and the Division of Neuropathology and Neurochemistry,
and Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology.
The project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie
Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
(FWF; grant PAT 4178023 to P.J.; grant DK W1232 to M.R.T. and J.G.D.) and the Austrian
Academy of Sciences (DOC fellowship 26137 to M.R.T.).
article_processing_charge: No
author:
- first_name: Jake F.
full_name: Watson, Jake F.
last_name: Watson
- first_name: Victor
full_name: Vargas-Barroso, Victor
last_name: Vargas-Barroso
- first_name: Rebecca J.
full_name: Morse-Mora, Rebecca J.
last_name: Morse-Mora
- first_name: Andrea
full_name: Navas-Olive, Andrea
last_name: Navas-Olive
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Matthias
full_name: Tomschik, Matthias
last_name: Tomschik
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Watson JF, Vargas-Barroso V, Morse-Mora RJ, et al. Human hippocampal CA3 uses
specific functional connectivity rules for efficient associative memory. bioRxiv.
doi:10.1101/2024.05.02.592169
apa: Watson, J. F., Vargas-Barroso, V., Morse-Mora, R. J., Navas-Olive, A., Tavakoli,
M., Danzl, J. G., … Jonas, P. M. (n.d.). Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv. https://doi.org/10.1101/2024.05.02.592169
chicago: Watson, Jake F., Victor Vargas-Barroso, Rebecca J. Morse-Mora, Andrea Navas-Olive,
Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M
Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for
Efficient Associative Memory.” BioRxiv, n.d. https://doi.org/10.1101/2024.05.02.592169.
ieee: J. F. Watson et al., “Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory,” bioRxiv. .
ista: Watson JF, Vargas-Barroso V, Morse-Mora RJ, Navas-Olive A, Tavakoli M, Danzl
JG, Tomschik M, Rössler K, Jonas PM. Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv, 10.1101/2024.05.02.592169.
mla: Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
Rules for Efficient Associative Memory.” BioRxiv, doi:10.1101/2024.05.02.592169.
short: J.F. Watson, V. Vargas-Barroso, R.J. Morse-Mora, A. Navas-Olive, M. Tavakoli,
J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-19T11:35:08Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-10-20T08:20:04Z
day: '02'
department:
- _id: JoDa
- _id: PeJo
doi: 10.1101/2024.05.02.592169
ec_funded: 1
fulldoi: https://doi.org/10.1101/2024.05.02.592169
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2024.05.02.592169
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
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call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
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name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
publication: bioRxiv
publication_status: draft
related_material:
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status: public
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relation: later_version
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status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
associative memory
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '14257'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanometer synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS uses fixation-compatible
extracellular labeling and optical imaging, including stimulated emission depletion
or expansion microscopy, to comprehensively delineate cellular structures. It
enables three-dimensional reconstruction of single synapses and mapping of synaptic
connectivity by identification and analysis of putative synaptic cleft regions.
Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed
and quantified the synaptic input and output structure of identified neurons.
We furthermore demonstrate applicability to clinically derived human tissue samples,
including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing
the cellular architecture of brain tissue in health and disease.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: LifeSc
- _id: M-Shop
- _id: E-Lib
acknowledgement: 'We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak
for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I.
Erber for technical assistance; and M. Tomschik for support with obtaining human
samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata
for computational support and hardware control. We are grateful to R. Shigemoto
and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University)
for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly
provided by S. Grant (University of Edinburgh). We acknowledge expert support by
Institute of Science and Technology Austria’s scientific computing, imaging and
optics, preclinical and lab support facilities and by the Miba machine shop and
library. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232
(J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award
(P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27
(R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.);
European Union’s Horizon 2020 research and innovation programme, European Research
Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020
research and innovation programme, European Research Council (ERC) grant 692692
– GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under
the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions
Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).'
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Nicole
full_name: Amberg, Nicole
id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87
last_name: Amberg
orcid: 0000-0002-3183-8207
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Romana
full_name: Höftberger, Romana
last_name: Höftberger
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture
across millimeter to nanometer scales. Nature Biotechnology. 2024;42:1051-1064.
doi:10.1038/s41587-023-01911-8
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (2024). Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture
across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer
Nature, 2024. https://doi.org/10.1038/s41587-023-01911-8.
ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter
to nanometer scales,” Nature Biotechnology, vol. 42. Springer Nature, pp.
1051–1064, 2024.
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino
G, Jonas PM, Danzl JG. 2024. Imaging brain tissue architecture across millimeter
to nanometer scales. Nature Biotechnology. 42, 1051–1064.
mla: Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter
to Nanometer Scales.” Nature Biotechnology, vol. 42, Springer Nature, 2024,
pp. 1051–64, doi:10.1038/s41587-023-01911-8.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S.
Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology 42 (2024) 1051–1064.
corr_author: '1'
das_tickbox: '1'
date_created: 2023-09-03T22:01:15Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-10-21T08:36:20Z
day: '01'
ddc:
- '570'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
- _id: Bio
- _id: RySh
doi: 10.1038/s41587-023-01911-8
ec_funded: 1
external_id:
isi:
- '001065254200001'
pmid:
- '37653226'
file:
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content_type: application/pdf
creator: dernst
date_created: 2025-01-09T07:48:01Z
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file_id: '18784'
file_name: 2024_NatureBiotech_Michalska.pdf
file_size: 26065165
relation: main_file
success: 1
file_date_updated: 2025-01-09T07:48:01Z
fulldoi: https://doi.org/10.1038/s41587-023-01911-8
has_accepted_license: '1'
intvolume: ' 42'
isi: 1
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1051-1064
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
grant_number: LS18-022
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Nature Biotechnology
publication_identifier:
eissn:
- 1546-1696
issn:
- 1087-0156
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/CATS
record:
- id: '18660'
relation: dissertation_contains
status: deleted
- id: '13126'
relation: research_data
status: public
- id: '18674'
relation: dissertation_contains
status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Imaging brain tissue architecture across millimeter to nanometer scales
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 42
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '14843'
abstract:
- lang: eng
text: The coupling between Ca2+ channels and release sensors is a key factor defining
the signaling properties of a synapse. However, the coupling nanotopography at
many synapses remains unknown, and it is unclear how it changes during development.
To address these questions, we examined coupling at the cerebellar inhibitory
basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
by paired recording and intracellular pipette perfusion revealed that the effects
of exogenous Ca2+ chelators decreased during development, despite constant reliance
of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
vesicles were only clustered at later developmental stages. Modeling suggested
a developmental transformation from a more random to a more clustered coupling
nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
configuration, optimizing speed, reliability, and energy efficiency of synaptic
transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
for advice on numerical solution of partial differential equations, Maria Reva for
help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
and Machine Shop). The project received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation program (grant
agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
(Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: JingJing
full_name: Chen, JingJing
id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Walter
full_name: Kaufmann, Walter
id: 3F99E422-F248-11E8-B48F-1D18A9856A87
last_name: Kaufmann
orcid: 0000-0001-9735-5315
- first_name: Chong
full_name: Chen, Chong
id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
last_name: Chen
- first_name: Itaru
full_name: Arai, Itaru
id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
last_name: Arai
- first_name: Olena
full_name: Kim, Olena
id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
last_name: Kim
orcid: 0000-0003-2344-1039
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse. Neuron. 2024;112(5):755-771.e9.
doi:10.1016/j.neuron.2023.12.002
apa: Chen, J., Kaufmann, W., Chen, C., Arai, itaru, Kim, O., Shigemoto, R., &
Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography
at a central GABAergic synapse. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2023.12.002
chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron. Elsevier, 2024.
https://doi.org/10.1016/j.neuron.2023.12.002.
ieee: J. Chen et al., “Developmental transformation of Ca2+ channel-vesicle
nanotopography at a central GABAergic synapse,” Neuron, vol. 112, no. 5.
Elsevier, p. 755–771.e9, 2024.
ista: Chen J, Kaufmann W, Chen C, Arai itaru, Kim O, Shigemoto R, Jonas PM. 2024.
Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic synapse. Neuron. 112(5), 755–771.e9.
mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
Nanotopography at a Central GABAergic Synapse.” Neuron, vol. 112, no. 5,
Elsevier, 2024, p. 755–771.e9, doi:10.1016/j.neuron.2023.12.002.
short: J. Chen, W. Kaufmann, C. Chen, itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
Neuron 112 (2024) 755–771.e9.
corr_author: '1'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-03-06T00:00:00Z
date_updated: 2026-10-25T23:31:20Z
day: '06'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
isi:
- '001202925700001'
pmid:
- '38215739'
file:
- access_level: open_access
checksum: 30098b4f0209556ddfb3540a23d07ca5
content_type: application/pdf
creator: dernst
date_created: 2025-04-23T14:02:08Z
date_updated: 2025-04-23T14:02:08Z
file_id: '19614'
file_name: 2024_Neuron_Chen.pdf
file_size: 8192355
relation: main_file
success: 1
file_date_updated: 2025-04-23T14:02:08Z
fulldoi: https://doi.org/10.1016/j.neuron.2023.12.002
has_accepted_license: '1'
intvolume: ' 112'
isi: 1
issue: '5'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 755-771.e9
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
grant_number: '25383'
name: Development of nanodomain coupling between Ca2+ channels and release sensors
at a central inhibitory synapse
publication: Neuron
publication_identifier:
eissn:
- 1097-4199
issn:
- 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/synapses-brought-to-the-point/
record:
- id: '15101'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
GABAergic synapse
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2024'
...
---
APC_amount: 5887,8 EUR
OA_place: publisher
OA_type: hybrid
_id: '15084'
abstract:
- lang: eng
text: "GABAB receptor (GBR) activation inhibits neurotransmitter release in axon
terminals in the brain, except in medial habenula (MHb) terminals, which show
robust potentiation. However, mechanisms underlying this enigmatic potentiation
remain elusive. Here, we report that GBR activation on MHb terminals induces an
activity-dependent transition from a facilitating, tonic to a depressing, phasic
neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase
in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked
synaptic vesicles (SVs) at the presynaptic active zone (AZ). Strikingly, the depressing
phasic release exhibits looser coupling distance than the tonic release. Furthermore,
the tonic and phasic release are selectively affected by deletion of synaptoporin
(SPO) and Ca\r\n 2+\r\n -dependent
activator protein for secretion 2 (CAPS2), respectively. SPO modulates augmentation,
the short-term plasticity associated with tonic release, and CAPS2 retains the
increased RRP for initial responses in phasic response trains. The cytosolic protein
CAPS2 showed a SV-associated distribution similar to the vesicular transmembrane
protein SPO, and they were colocalized in the same terminals. We developed the
“Flash and Freeze-fracture” method, and revealed the release of SPO-associated
vesicles in both tonic and phasic modes and activity-dependent recruitment of
CAPS2 to the AZ during phasic release, which lasted several minutes. Overall,
these results indicate that GBR activation translocates CAPS2 to the AZ along
with the fusion of CAPS2-associated SVs, contributing to persistency of the RRP
increase. Thus, we identified structural and molecular mechanisms underlying tonic
and phasic neurotransmitter release and their transition by GBR activation in
MHb terminals."
acknowledged_ssus:
- _id: M-Shop
- _id: PreCl
- _id: EM-Fac
acknowledgement: We thank Erwin Neher and Ipe Ninan for critical comments on the manuscript.
This project has received funding from the European Research Council (ERC) and European
Commission, under the European Union’s Horizon 2020 research and innovation program
(ERC grant agreement no. 694539 to R.S. and the Marie Skłodowska-Curie grant agreement
no. 665385 to C.Ö.). This study was supported by the Cooperative Study Program of
Center for Animal Resources and Collaborative Study of NINS. We thank Kohgaku Eguchi
for statistical analysis, Yu Kasugai for additional EM imaging, Robert Beattie for
the design of the slice recovery chamber for Flash and Freeze experiments, Todor
Asenov from the ISTA machine shop for custom part preparations for high-pressure
freezing, the ISTA preclinical facility for animal caretaking, and the ISTA EM facilities
for technical support.
article_number: e2301449121
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Peter
full_name: Koppensteiner, Peter
id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
last_name: Koppensteiner
orcid: 0000-0002-3509-1948
- first_name: Pradeep
full_name: Bhandari, Pradeep
id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
last_name: Bhandari
orcid: 0000-0003-0863-4481
- first_name: Hüseyin C
full_name: Önal, Hüseyin C
id: 4659D740-F248-11E8-B48F-1D18A9856A87
last_name: Önal
orcid: 0000-0002-2771-2011
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Elodie
full_name: Le Monnier, Elodie
id: 3B59276A-F248-11E8-B48F-1D18A9856A87
last_name: Le Monnier
- first_name: Utsa
full_name: Roy, Utsa
id: 4d26cf11-5355-11ee-ae5a-eb05e255b9b2
last_name: Roy
- first_name: Yukihiro
full_name: Nakamura, Yukihiro
last_name: Nakamura
- first_name: Tetsushi
full_name: Sadakata, Tetsushi
last_name: Sadakata
- first_name: Makoto
full_name: Sanbo, Makoto
last_name: Sanbo
- first_name: Masumi
full_name: Hirabayashi, Masumi
last_name: Hirabayashi
- first_name: JeongSeop
full_name: Rhee, JeongSeop
last_name: Rhee
- first_name: Nils
full_name: Brose, Nils
last_name: Brose
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Ryuichi
full_name: Shigemoto, Ryuichi
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Koppensteiner P, Bhandari P, Önal C, et al. GABAB receptors induce phasic release
from medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences of the United States
of America. 2024;121(8). doi:10.1073/pnas.2301449121
apa: Koppensteiner, P., Bhandari, P., Önal, C., Borges Merjane, C., Le Monnier,
E., Roy, U., … Shigemoto, R. (2024). GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles. Proceedings of the National Academy of Sciences of the United States
of America. National Academy of Sciences. https://doi.org/10.1073/pnas.2301449121
chicago: Koppensteiner, Peter, Pradeep Bhandari, Cihan Önal, Carolina Borges Merjane,
Elodie Le Monnier, Utsa Roy, Yukihiro Nakamura, et al. “GABAB Receptors Induce
Phasic Release from Medial Habenula Terminals through Activity-Dependent Recruitment
of Release-Ready Vesicles.” Proceedings of the National Academy of Sciences
of the United States of America. National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2301449121.
ieee: P. Koppensteiner et al., “GABAB receptors induce phasic release from
medial habenula terminals through activity-dependent recruitment of release-ready
vesicles,” Proceedings of the National Academy of Sciences of the United States
of America, vol. 121, no. 8. National Academy of Sciences, 2024.
ista: Koppensteiner P, Bhandari P, Önal C, Borges Merjane C, Le Monnier E, Roy U,
Nakamura Y, Sadakata T, Sanbo M, Hirabayashi M, Rhee J, Brose N, Jonas PM, Shigemoto
R. 2024. GABAB receptors induce phasic release from medial habenula terminals
through activity-dependent recruitment of release-ready vesicles. Proceedings
of the National Academy of Sciences of the United States of America. 121(8), e2301449121.
mla: Koppensteiner, Peter, et al. “GABAB Receptors Induce Phasic Release from Medial
Habenula Terminals through Activity-Dependent Recruitment of Release-Ready Vesicles.”
Proceedings of the National Academy of Sciences of the United States of America,
vol. 121, no. 8, e2301449121, National Academy of Sciences, 2024, doi:10.1073/pnas.2301449121.
short: P. Koppensteiner, P. Bhandari, C. Önal, C. Borges Merjane, E. Le Monnier,
U. Roy, Y. Nakamura, T. Sadakata, M. Sanbo, M. Hirabayashi, J. Rhee, N. Brose,
P.M. Jonas, R. Shigemoto, Proceedings of the National Academy of Sciences of the
United States of America 121 (2024).
corr_author: '1'
das_tickbox: '1'
date_created: 2024-03-05T09:23:55Z
date_published: 2024-02-20T00:00:00Z
date_updated: 2026-10-25T23:31:31Z
day: '20'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.1073/pnas.2301449121
ec_funded: 1
external_id:
isi:
- '001208567300006'
pmid:
- '38346189'
file:
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checksum: b25b2a057c266ff317a48b0d54d6fc8a
content_type: application/pdf
creator: dernst
date_created: 2024-03-12T13:42:42Z
date_updated: 2024-03-12T13:42:42Z
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file_name: 2024_PNAS_Koppensteiner.pdf
file_size: 13648221
relation: main_file
success: 1
file_date_updated: 2024-03-12T13:42:42Z
fulldoi: https://doi.org/10.1073/pnas.2301449121
has_accepted_license: '1'
intvolume: ' 121'
isi: 1
issue: '8'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '694539'
name: 'In situ analysis of single channel subunit composition in neurons: physiological
implication in synaptic plasticity and behaviour'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Proceedings of the National Academy of Sciences of the United States
of America
publication_identifier:
eissn:
- 1091-6490
issn:
- 0027-8424
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on ISTA Website
relation: press_release
url: https://ista.ac.at/en/news/neuronal-insights-flash-and-freeze-fracture/
record:
- id: '13173'
relation: research_data
status: public
- id: '19271'
relation: dissertation_contains
status: public
researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: GABAB receptors induce phasic release from medial habenula terminals through
activity-dependent recruitment of release-ready vesicles
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 121
year: '2024'
...
---
_id: '12759'
abstract:
- lang: eng
text: Stereological methods for estimating the 3D particle size and density from
2D projections are essential to many research fields. These methods are, however,
prone to errors arising from undetected particle profiles due to sectioning and
limited resolution, known as ‘lost caps’. A potential solution developed by Keiding,
Jensen, and Ranek in 1972, which we refer to as the Keiding model, accounts for
lost caps by quantifying the smallest detectable profile in terms of its limiting
‘cap angle’ (ϕ), a size-independent measure of a particle’s distance from the
section surface. However, this simple solution has not been widely adopted nor
tested. Rather, model-independent design-based stereological methods, which do
not explicitly account for lost caps, have come to the fore. Here, we provide
the first experimental validation of the Keiding model by comparing the size and
density of particles estimated from 2D projections with direct measurement from
3D EM reconstructions of the same tissue. We applied the Keiding model to estimate
the size and density of somata, nuclei and vesicles in the cerebellum of mice
and rats, where high packing density can be problematic for design-based methods.
Our analysis reveals a Gaussian distribution for ϕ rather than a single value.
Nevertheless, curve fits of the Keiding model to the 2D diameter distribution
accurately estimate the mean ϕ and 3D diameter distribution. While systematic
testing using simulations revealed an upper limit to determining ϕ, our analysis
shows that estimated ϕ can be used to determine the 3D particle density from the
2D density under a wide range of conditions, and this method is potentially more
accurate than minimum-size-based lost-cap corrections and disector methods. Our
results show the Keiding model provides an efficient means of accurately estimating
the size and density of particles from 2D projections even under conditions of
a high density.
acknowledged_ssus:
- _id: EM-Fac
acknowledgement: "We thank the IST Austria Electron Microscopy Facility for technical
support, and Diccon Coyle, Andrea Lőrincz and Zoltan Nusser for their helpful comments
and discussions.\r\nFunding for JSR and RAS was from the Wellcome Trust (203048;
224499; https://\r\nwellcome.org/). RAS is in receipt of a Wellcome Trust Principal
Research Fellowship (224499).\r\nFunding for CBM and PJ was from Fond zur Förderung
der Wissenschaftlichen Forschung (V\r\n739-B27 Elise-Richter Programme to CBM, Z
312-B27 Wittgenstein Award to PJ; \r\nhttps://www.fwf.ac.at). PJ received funding
from the European Research Council (ERC; https://erc.europa.eu) under the European
Union’s Horizon 2020 research and innovation programme (grant agreement no. 692692).
NH was supported by a European\r\nResearch Council Advanced Grant (ERC-AG787157)."
article_number: e0277148
article_processing_charge: No
article_type: original
author:
- first_name: Jason Seth
full_name: Rothman, Jason Seth
last_name: Rothman
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Noemi
full_name: Holderith, Noemi
last_name: Holderith
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: R.
full_name: Angus Silver, R.
last_name: Angus Silver
citation:
ama: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. Validation
of a stereological method for estimating particle size and density from 2D projections
with high accuracy. PLoS ONE. 2023;18(3 March). doi:10.1371/journal.pone.0277148
apa: Rothman, J. S., Borges Merjane, C., Holderith, N., Jonas, P. M., & Angus
Silver, R. (2023). Validation of a stereological method for estimating particle
size and density from 2D projections with high accuracy. PLoS ONE. Public
Library of Science. https://doi.org/10.1371/journal.pone.0277148
chicago: Rothman, Jason Seth, Carolina Borges Merjane, Noemi Holderith, Peter M
Jonas, and R. Angus Silver. “Validation of a Stereological Method for Estimating
Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE.
Public Library of Science, 2023. https://doi.org/10.1371/journal.pone.0277148.
ieee: J. S. Rothman, C. Borges Merjane, N. Holderith, P. M. Jonas, and R. Angus
Silver, “Validation of a stereological method for estimating particle size and
density from 2D projections with high accuracy,” PLoS ONE, vol. 18, no.
3 March. Public Library of Science, 2023.
ista: Rothman JS, Borges Merjane C, Holderith N, Jonas PM, Angus Silver R. 2023.
Validation of a stereological method for estimating particle size and density
from 2D projections with high accuracy. PLoS ONE. 18(3 March), e0277148.
mla: Rothman, Jason Seth, et al. “Validation of a Stereological Method for Estimating
Particle Size and Density from 2D Projections with High Accuracy.” PLoS ONE,
vol. 18, no. 3 March, e0277148, Public Library of Science, 2023, doi:10.1371/journal.pone.0277148.
short: J.S. Rothman, C. Borges Merjane, N. Holderith, P.M. Jonas, R. Angus Silver,
PLoS ONE 18 (2023).
date_created: 2023-03-26T22:01:07Z
date_published: 2023-03-17T00:00:00Z
date_updated: 2025-04-23T08:50:50Z
day: '17'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1371/journal.pone.0277148
ec_funded: 1
external_id:
isi:
- '001024737400001'
pmid:
- '36930689'
file:
- access_level: open_access
checksum: 2380331ec27cc87808826fc64419ac1c
content_type: application/pdf
creator: dernst
date_created: 2023-03-27T06:51:09Z
date_updated: 2023-03-27T06:51:09Z
file_id: '12770'
file_name: 2023_PLoSOne_Rothman.pdf
file_size: 7290413
relation: main_file
success: 1
file_date_updated: 2023-03-27T06:51:09Z
fulldoi: https://doi.org/10.1371/journal.pone.0277148
has_accepted_license: '1'
intvolume: ' 18'
isi: 1
issue: 3 March
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 2696E7FE-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00739
name: Structural plasticity at mossy fiber-CA3 synapses
publication: PLoS ONE
publication_identifier:
eissn:
- 1932-6203
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Validation of a stereological method for estimating particle size and density
from 2D projections with high accuracy
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 18
year: '2023'
...
---
OA_place: publisher
OA_type: hybrid
_id: '13267'
abstract:
- lang: eng
text: Three-dimensional (3D) reconstruction of living brain tissue down to an individual
synapse level would create opportunities for decoding the dynamics and structure–function
relationships of the brain’s complex and dense information processing network;
however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise
ratio and prohibitive light burden in optical imaging, whereas electron microscopy
is inherently static. Here we solved these challenges by developing an integrated
optical/machine-learning technology, LIONESS (live information-optimized nanoscopy
enabling saturated segmentation). This leverages optical modifications to stimulated
emission depletion microscopy in comprehensively, extracellularly labeled tissue
and previous information on sample structure via machine learning to simultaneously
achieve isotropic super-resolution, high signal-to-noise ratio and compatibility
with living tissue. This allows dense deep-learning-based instance segmentation
and 3D reconstruction at a synapse level, incorporating molecular, activity and
morphodynamic information. LIONESS opens up avenues for studying the dynamic functional
(nano-)architecture of living brain tissue.
acknowledged_ssus:
- _id: ScienComp
- _id: Bio
- _id: PreCl
- _id: E-Lib
- _id: LifeSc
- _id: M-Shop
acknowledgement: "We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance
and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata
for hardware control support and M. Cunha dos Santos for initial exploration of
software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt,
S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L.
Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We
acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and
optics, preclinical, library and laboratory support facilities and by the Miba machine
shop. We gratefully acknowledge funding by the following sources: Austrian Science
Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.)
and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung
NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D.
and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska
Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research
and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE
(B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.);
and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research
Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development
grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship
no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier
Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science
Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.)."
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
orcid: 0000-0003-0201-2315
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G.N.
full_name: Grant, Seth G.N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction
of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D.,
Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain
tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik,
Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction
of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.
ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain
tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.
ista: Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson
J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen
J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense
4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.
mla: Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain
Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin,
J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri,
J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel,
J.G. Danzl, Nature Methods 20 (2023) 1256–1265.
corr_author: '1'
date_created: 2023-07-23T22:01:13Z
date_published: 2023-08-01T00:00:00Z
date_updated: 2026-10-02T11:27:12Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
- _id: Bio
doi: 10.1038/s41592-023-01936-6
ec_funded: 1
external_id:
isi:
- '001025621500001'
pmid:
- '37429995'
file:
- access_level: open_access
checksum: a68e845780a82ea36d0d4d3212a87c10
content_type: application/pdf
creator: dernst
date_created: 2025-02-26T08:01:57Z
date_updated: 2025-02-26T08:01:57Z
file_id: '19088'
file_name: 2023_NatureMethods_Velicky.pdf
file_size: 14103039
relation: main_file
success: 1
file_date_updated: 2025-02-26T08:01:57Z
fulldoi: https://doi.org/10.1038/s41592-023-01936-6
has_accepted_license: '1'
intvolume: ' 20'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 1256-1265
pmid: 1
project:
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 2548AE96-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232
name: Molecular Drug Targets
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 23889792-32DE-11EA-91FC-C7463DDC885E
grant_number: LS18-022
name: High content imaging to decode human immune cell interactions in health and
allergic disease
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
- _id: 24F9549A-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715767'
name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and
Modeling'
- _id: 25444568-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '715508'
name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
and in vitro Models
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 2668BFA0-B435-11E9-9278-68D0E5697425
grant_number: LT00057
name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration
publication: Nature Methods
publication_identifier:
eissn:
- 1548-7105
issn:
- 1548-7091
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/danzllab/LIONESS
record:
- id: '12817'
relation: research_data
status: public
- id: '14770'
relation: shorter_version
status: public
- id: '11943'
relation: earlier_version
status: public
- id: '18674'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Dense 4D nanoscale reconstruction of living brain tissue
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 20
year: '2023'
...
---
_id: '11951'
abstract:
- lang: eng
text: The mammalian hippocampal formation (HF) plays a key role in several higher
brain functions, such as spatial coding, learning and memory. Its simple circuit
architecture is often viewed as a trisynaptic loop, processing input originating
from the superficial layers of the entorhinal cortex (EC) and sending it back
to its deeper layers. Here, we show that excitatory neurons in layer 6b of the
mouse EC project to all sub-regions comprising the HF and receive input from the
CA1, thalamus and claustrum. Furthermore, their output is characterized by unique
slow-decaying excitatory postsynaptic currents capable of driving plateau-like
potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b
pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs
not only acquisition of new spatial memories, but also degradation of previously
acquired ones. Our results provide evidence of a functional role for cortical
layer 6b neurons in the adult brain.
acknowledged_ssus:
- _id: Bio
- _id: SSU
acknowledgement: We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller
for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility
of the Institute of Science and Technology Austria (ISTA) for image analysis scripts
and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel
Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for
help with single-unit clustering. Finally, we also thank B. Suter for discussions,
A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of
the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service
Units of ISTA for efficient support. This project was funded by the European Research
Council (ERC) under the European Union’s Horizon 2020 research and innovation programme
(ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.).
article_number: '4826'
article_processing_charge: No
article_type: original
author:
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Karola
full_name: Käfer, Karola
id: 2DAA49AA-F248-11E8-B48F-1D18A9856A87
last_name: Käfer
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Jozsef L
full_name: Csicsvari, Jozsef L
id: 3FA14672-F248-11E8-B48F-1D18A9856A87
last_name: Csicsvari
orcid: 0000-0002-5193-4036
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct
excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes
to spatial coding and memory. Nature Communications. 2022;13. doi:10.1038/s41467-022-32559-8
apa: Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., &
Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons
to the hippocampus contributes to spatial coding and memory. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-022-32559-8
chicago: Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann
G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer
6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature
Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32559-8.
ieee: Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M.
Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the
hippocampus contributes to spatial coding and memory,” Nature Communications,
vol. 13. Springer Nature, 2022.
ista: Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A
direct excitatory projection from entorhinal layer 6b neurons to the hippocampus
contributes to spatial coding and memory. Nature Communications. 13, 4826.
mla: Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer
6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature
Communications, vol. 13, 4826, Springer Nature, 2022, doi:10.1038/s41467-022-32559-8.
short: Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas,
Nature Communications 13 (2022).
corr_author: '1'
date_created: 2022-08-24T08:25:50Z
date_published: 2022-08-16T00:00:00Z
date_updated: 2025-06-12T06:10:44Z
day: '16'
ddc:
- '570'
department:
- _id: JoCs
- _id: PeJo
- _id: JoDa
doi: 10.1038/s41467-022-32559-8
ec_funded: 1
external_id:
isi:
- '000841396400008'
pmid:
- '35974109'
file:
- access_level: open_access
checksum: 405936d9e4d33625d80c093c9713a91f
content_type: application/pdf
creator: dernst
date_created: 2022-08-26T11:51:40Z
date_updated: 2022-08-26T11:51:40Z
file_id: '11990'
file_name: 2022_NatureCommunications_BenSimon.pdf
file_size: 5910357
relation: main_file
success: 1
file_date_updated: 2022-08-26T11:51:40Z
fulldoi: https://doi.org/10.1038/s41467-022-32559-8
has_accepted_license: '1'
intvolume: ' 13'
isi: 1
keyword:
- General Physics and Astronomy
- General Biochemistry
- Genetics and Molecular Biology
- General Chemistry
- Multidisciplinary
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 265CB4D0-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: I03600
name: Optical control of synaptic function via adhesion molecules
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus
contributes to spatial coding and memory
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 13
year: '2022'
...
---
_id: '12288'
abstract:
- lang: eng
text: To understand the function of neuronal circuits, it is crucial to disentangle
the connectivity patterns within the network. However, most tools currently used
to explore connectivity have low throughput, low selectivity, or limited accessibility.
Here, we report the development of an improved packaging system for the production
of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers
orders of magnitude higher with no background contamination, at a fraction of
the production time, while preserving the efficiency of transsynaptic labeling.
Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic
RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal
populations, tailored for diverse experimental requirements. We demonstrate the
power and flexibility of the new system by uncovering hidden local and distal
inhibitory connections in the mouse hippocampal formation and by imaging the functional
properties of a cortical microcircuit across weeks. Our novel production pipeline
provides a convenient approach to generate new rabies vectors, while our toolkit
flexibly and efficiently expands the current capacity to label, manipulate and
image the neuronal activity of interconnected neuronal circuits in vitro and in
vivo.
acknowledged_ssus:
- _id: Bio
- _id: PreCl
acknowledgement: We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c
viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript.
This research was supported by the Scientific Service Units (SSU) of IST-Austria
through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical
Facility (PCF). This project was funded by the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation programme (ERC advanced
grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der
Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier
Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).
article_number: '79848'
article_processing_charge: No
article_type: original
author:
- first_name: Anton L
full_name: Sumser, Anton L
id: 3320A096-F248-11E8-B48F-1D18A9856A87
last_name: Sumser
orcid: 0000-0002-4792-1881
- first_name: Maximilian A
full_name: Jösch, Maximilian A
id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
last_name: Jösch
orcid: 0000-0002-3937-1330
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
citation:
ama: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production
of improved rabies viral vectors for specific, efficient and versatile transsynaptic
retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848
apa: Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast,
high-throughput production of improved rabies viral vectors for specific, efficient
and versatile transsynaptic retrograde labeling. ELife. eLife Sciences
Publications. https://doi.org/10.7554/elife.79848
chicago: Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon.
“Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific,
Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife
Sciences Publications, 2022. https://doi.org/10.7554/elife.79848.
ieee: A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput
production of improved rabies viral vectors for specific, efficient and versatile
transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production
of improved rabies viral vectors for specific, efficient and versatile transsynaptic
retrograde labeling. eLife. 11, 79848.
mla: Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies
Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.”
ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848.
short: A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).
corr_author: '1'
date_created: 2023-01-16T10:04:15Z
date_published: 2022-09-15T00:00:00Z
date_updated: 2025-04-15T08:29:05Z
day: '15'
ddc:
- '570'
department:
- _id: MaJö
- _id: PeJo
doi: 10.7554/elife.79848
ec_funded: 1
external_id:
isi:
- '000892204300001'
pmid:
- '36040301'
file:
- access_level: open_access
checksum: 5a2a65e3e7225090c3d8199f3bbd7b7b
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T11:50:53Z
date_updated: 2023-01-30T11:50:53Z
file_id: '12463'
file_name: 2022_eLife_Sumser.pdf
file_size: 8506811
relation: main_file
success: 1
file_date_updated: 2023-01-30T11:50:53Z
fulldoi: https://doi.org/10.7554/elife.79848
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 2634E9D2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '756502'
name: Circuits of Visual Attention
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 266D407A-B435-11E9-9278-68D0E5697425
grant_number: LT000256
name: Neuronal networks of salience and spatial detection in the murine superior
colliculus
- _id: 264FEA02-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1098-2017
name: Connecting sensory with motor processing in the superior colliculus
publication: eLife
publication_identifier:
eissn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Fast, high-throughput production of improved rabies viral vectors for specific,
efficient and versatile transsynaptic retrograde labeling
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2022'
...
---
OA_place: repository
_id: '11943'
abstract:
- lang: eng
text: Complex wiring between neurons underlies the information-processing network
enabling all brain functions, including cognition and memory. For understanding
how the network is structured, processes information, and changes over time, comprehensive
visualization of the architecture of living brain tissue with its cellular and
molecular components would open up major opportunities. However, electron microscopy
(EM) provides nanometre-scale resolution required for full in-silico
reconstruction1–5, yet is limited to fixed specimens and
static representations. Light microscopy allows live observation, with super-resolution
approaches6–12 facilitating nanoscale visualization, but
comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue
photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise
ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue.
We developed an integrated imaging and analysis technology, adapting stimulated
emission depletion (STED) microscopy6,13 in extracellularly
labelled tissue14 for high SNR and near-isotropic resolution.
Centrally, a two-stage deep-learning approach leveraged previously obtained information
on sample structure to drastically reduce photo-burden and enable automated volumetric
reconstruction down to single synapse level. Live reconstruction provides unbiased
analysis of tissue architecture across time in relation to functional activity
and targeted activation, and contextual understanding of molecular labelling.
This adoptable technology will facilitate novel insights into the dynamic functional
architecture of living brain tissue.
article_processing_charge: No
author:
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Eder
full_name: Miguel Villalba, Eder
id: 3FB91342-F248-11E8-B48F-1D18A9856A87
last_name: Miguel Villalba
orcid: 0000-0001-5665-0430
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Donglai
full_name: Wei, Donglai
last_name: Wei
- first_name: Zudi
full_name: Lin, Zudi
last_name: Lin
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Jakob
full_name: Troidl, Jakob
last_name: Troidl
- first_name: Johanna
full_name: Beyer, Johanna
last_name: Beyer
- first_name: Yoav
full_name: Ben Simon, Yoav
id: 43DF3136-F248-11E8-B48F-1D18A9856A87
last_name: Ben Simon
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Wiebke
full_name: Jahr, Wiebke
id: 425C1CE8-F248-11E8-B48F-1D18A9856A87
last_name: Jahr
orcid: 0000-0003-0201-2315
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Johannes
full_name: Broichhagen, Johannes
last_name: Broichhagen
- first_name: Seth G. N.
full_name: Grant, Seth G. N.
last_name: Grant
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Hanspeter
full_name: Pfister, Hanspeter
last_name: Pfister
- first_name: Bernd
full_name: Bickel, Bernd
id: 49876194-F248-11E8-B48F-1D18A9856A87
last_name: Bickel
orcid: 0000-0001-6511-9385
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction
of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431
apa: Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson,
J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv.
https://doi.org/10.1101/2022.03.16.484431
chicago: Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei,
Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living
Brain Tissue.” BioRxiv, n.d. https://doi.org/10.1101/2022.03.16.484431.
ieee: P. Velicky et al., “Saturated reconstruction of living brain tissue,”
bioRxiv. .
ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl
J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN,
Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction
of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.
mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.”
BioRxiv, doi:10.1101/2022.03.16.484431.
short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson,
J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen,
S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv
(n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2022-08-23T11:07:59Z
date_published: 2022-05-09T00:00:00Z
date_updated: 2026-10-25T23:31:00Z
day: '09'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
doi: 10.1101/2022.03.16.484431
fulldoi: https://doi.org/10.1101/2022.03.16.484431
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.03.16.484431
month: '05'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: draft
related_material:
record:
- id: '13267'
relation: later_version
status: public
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Saturated reconstruction of living brain tissue
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '11950'
abstract:
- lang: eng
text: Mapping the complex and dense arrangement of cells and their connectivity
in brain tissue demands nanoscale spatial resolution imaging. Super-resolution
optical microscopy excels at visualizing specific molecules and individual cells
but fails to provide tissue context. Here we developed Comprehensive Analysis
of Tissues across Scales (CATS), a technology to densely map brain tissue architecture
from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed
brain preparations, including rodent and human. CATS leverages fixation-compatible
extracellular labeling and advanced optical readout, in particular stimulated-emission
depletion and expansion microscopy, to comprehensively delineate cellular structures.
It enables 3D-reconstructing single synapses and mapping synaptic connectivity
by identification and tailored analysis of putative synaptic cleft regions. Applying
CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal
the system’s molecularly informed ultrastructure across spatial scales and assess
local connectivity by reconstructing and quantifying the synaptic input and output
structure of identified neurons.
article_processing_charge: No
author:
- first_name: Julia M
full_name: Michalska, Julia M
id: 443DB6DE-F248-11E8-B48F-1D18A9856A87
last_name: Michalska
orcid: 0000-0003-3862-1235
- first_name: Julia
full_name: Lyudchik, Julia
id: 46E28B80-F248-11E8-B48F-1D18A9856A87
last_name: Lyudchik
- first_name: Philipp
full_name: Velicky, Philipp
id: 39BDC62C-F248-11E8-B48F-1D18A9856A87
last_name: Velicky
orcid: 0000-0002-2340-7431
- first_name: Hana
full_name: Korinkova, Hana
id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed
last_name: Korinkova
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Alban
full_name: Cenameri, Alban
id: 9ac8f577-2357-11eb-997a-e566c5550886
last_name: Cenameri
- first_name: Christoph M
full_name: Sommer, Christoph M
id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87
last_name: Sommer
orcid: 0000-0003-1216-9105
- first_name: Alessandro
full_name: Venturino, Alessandro
id: 41CB84B2-F248-11E8-B48F-1D18A9856A87
last_name: Venturino
orcid: 0000-0003-2356-9403
- first_name: Karl
full_name: Roessler, Karl
last_name: Roessler
- first_name: Thomas
full_name: Czech, Thomas
last_name: Czech
- first_name: Sandra
full_name: Siegert, Sandra
id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
last_name: Siegert
orcid: 0000-0001-8635-0877
- first_name: Gaia
full_name: Novarino, Gaia
id: 3E57A680-F248-11E8-B48F-1D18A9856A87
last_name: Novarino
orcid: 0000-0002-7673-7178
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
citation:
ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture
across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272
apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri,
A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales
with super-resolution light microscopy. bioRxiv. https://doi.org/10.1101/2022.08.17.504272
chicago: Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake
Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture
across Scales with Super-Resolution Light Microscopy.” BioRxiv, n.d. https://doi.org/10.1101/2022.08.17.504272.
ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across
scales with super-resolution light microscopy,” bioRxiv. .
ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer
CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG.
Uncovering brain tissue architecture across scales with super-resolution light
microscopy. bioRxiv, 10.1101/2022.08.17.504272.
mla: Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales
with Super-Resolution Light Microscopy.” BioRxiv, doi:10.1101/2022.08.17.504272.
short: J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri,
C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M.
Jonas, J.G. Danzl, BioRxiv (n.d.).
corr_author: '1'
das_tickbox: '1'
date_created: 2022-08-24T08:24:52Z
date_published: 2022-08-18T00:00:00Z
date_updated: 2026-10-25T23:31:00Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 10.1101/2022.08.17.504272
fulldoi: https://doi.org/10.1101/2022.08.17.504272
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2022.08.17.504272
month: '08'
oa: 1
oa_version: Preprint
publication: bioRxiv
publication_status: draft
related_material:
record:
- id: '12470'
relation: dissertation_contains
status: public
status: public
title: Uncovering brain tissue architecture across scales with super-resolution light
microscopy
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2022'
...
---
_id: '9329'
abstract:
- lang: eng
text: "Background: To understand information coding in single neurons, it is necessary
to analyze subthreshold synaptic events, action potentials (APs), and their interrelation
in different behavioral states. However, detecting excitatory postsynaptic potentials
(EPSPs) or currents (EPSCs) in behaving animals remains challenging, because of
unfavorable signal-to-noise ratio, high frequency, fluctuating amplitude, and
variable time course of synaptic events.\r\nNew method: We developed a method
for synaptic event detection, termed MOD (Machine-learning Optimal-filtering Detection-procedure),
which combines concepts of supervised machine learning and optimal Wiener filtering.
Experts were asked to manually score short epochs of data. The algorithm was trained
to obtain the optimal filter coefficients of a Wiener filter and the optimal detection
threshold. Scored and unscored data were then processed with the optimal filter,
and events were detected as peaks above threshold.\r\nResults: We challenged MOD
with EPSP traces in vivo in mice during spatial navigation and EPSC traces in
vitro in slices under conditions of enhanced transmitter release. The area under
the curve (AUC) of the receiver operating characteristics (ROC) curve was, on
average, 0.894 for in vivo and 0.969 for in vitro data sets, indicating high detection
accuracy and efficiency.\r\nComparison with existing methods: When benchmarked
using a (1 − AUC)−1 metric, MOD outperformed previous methods (template-fit, deconvolution,
and Bayesian methods) by an average factor of 3.13 for in vivo data sets, but
showed comparable (template-fit, deconvolution) or higher (Bayesian) computational
efficacy.\r\nConclusions: MOD may become an important new tool for large-scale,
real-time analysis of synaptic activity."
acknowledged_ssus:
- _id: SSU
acknowledgement: This project has received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement number 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
Forschung (Z 312-B27, Wittgenstein award to P.J.). We thank Drs. Jozsef Csicsvari,
Christoph Lampert, and Federico Stella for critically reading previous manuscript
versions. We are also grateful to Drs. Josh Merel and Ben Shababo for their help
with applying the Bayesian detection method to our data. We also thank Florian Marr
for technical assistance, Eleftheria Kralli-Beller for manuscript editing, and the
Scientific Service Units of IST Austria for efficient support.
article_number: '109125'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. MOD: A novel machine-learning optimal-filtering
method for accurate and efficient detection of subthreshold synaptic events in
vivo. Journal of Neuroscience Methods. 2021;357(6). doi:10.1016/j.jneumeth.2021.109125'
apa: 'Zhang, X., Schlögl, A., Vandael, D. H., & Jonas, P. M. (2021). MOD: A
novel machine-learning optimal-filtering method for accurate and efficient detection
of subthreshold synaptic events in vivo. Journal of Neuroscience Methods.
Elsevier. https://doi.org/10.1016/j.jneumeth.2021.109125'
chicago: 'Zhang, Xiaomin, Alois Schlögl, David H Vandael, and Peter M Jonas. “MOD:
A Novel Machine-Learning Optimal-Filtering Method for Accurate and Efficient Detection
of Subthreshold Synaptic Events in Vivo.” Journal of Neuroscience Methods.
Elsevier, 2021. https://doi.org/10.1016/j.jneumeth.2021.109125.'
ieee: 'X. Zhang, A. Schlögl, D. H. Vandael, and P. M. Jonas, “MOD: A novel machine-learning
optimal-filtering method for accurate and efficient detection of subthreshold
synaptic events in vivo,” Journal of Neuroscience Methods, vol. 357, no.
6. Elsevier, 2021.'
ista: 'Zhang X, Schlögl A, Vandael DH, Jonas PM. 2021. MOD: A novel machine-learning
optimal-filtering method for accurate and efficient detection of subthreshold
synaptic events in vivo. Journal of Neuroscience Methods. 357(6), 109125.'
mla: 'Zhang, Xiaomin, et al. “MOD: A Novel Machine-Learning Optimal-Filtering Method
for Accurate and Efficient Detection of Subthreshold Synaptic Events in Vivo.”
Journal of Neuroscience Methods, vol. 357, no. 6, 109125, Elsevier, 2021,
doi:10.1016/j.jneumeth.2021.109125.'
short: X. Zhang, A. Schlögl, D.H. Vandael, P.M. Jonas, Journal of Neuroscience Methods
357 (2021).
date_created: 2021-04-18T22:01:39Z
date_published: 2021-03-09T00:00:00Z
date_updated: 2025-06-12T06:39:15Z
day: '09'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1016/j.jneumeth.2021.109125
ec_funded: 1
external_id:
isi:
- '000661088500005'
pmid:
- '33711356'
file:
- access_level: open_access
checksum: 2a5800d91b96d08b525e17319dcd5e44
content_type: application/pdf
creator: dernst
date_created: 2021-04-19T08:30:22Z
date_updated: 2021-04-19T08:30:22Z
file_id: '9339'
file_name: 2021_JourNeuroscienceMeth_Zhang.pdf
file_size: 6924738
relation: main_file
success: 1
file_date_updated: 2021-04-19T08:30:22Z
fulldoi: https://doi.org/10.1016/j.jneumeth.2021.109125
has_accepted_license: '1'
intvolume: ' 357'
isi: 1
issue: '6'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
publication: Journal of Neuroscience Methods
publication_identifier:
eissn:
- 1872-678X
issn:
- 0165-0270
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'MOD: A novel machine-learning optimal-filtering method for accurate and efficient
detection of subthreshold synaptic events in vivo'
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 357
year: '2021'
...
---
OA_place: publisher
OA_type: gold
_id: '9778'
abstract:
- lang: eng
text: The hippocampal mossy fiber synapse is a key synapse of the trisynaptic circuit.
Post-tetanic potentiation (PTP) is the most powerful form of plasticity at this
synaptic connection. It is widely believed that mossy fiber PTP is an entirely
presynaptic phenomenon, implying that PTP induction is input-specific, and requires
neither activity of multiple inputs nor stimulation of postsynaptic neurons. To
directly test cooperativity and associativity, we made paired recordings between
single mossy fiber terminals and postsynaptic CA3 pyramidal neurons in rat brain
slices. By stimulating non-overlapping mossy fiber inputs converging onto single
CA3 neurons, we confirm that PTP is input-specific and non-cooperative. Unexpectedly,
mossy fiber PTP exhibits anti-associative induction properties. EPSCs show only
minimal PTP after combined pre- and postsynaptic high-frequency stimulation with
intact postsynaptic Ca2+ signaling, but marked PTP in the absence of postsynaptic
spiking and after suppression of postsynaptic Ca2+ signaling (10 mM EGTA). PTP
is largely recovered by inhibitors of voltage-gated R- and L-type Ca2+ channels,
group II mGluRs, and vacuolar-type H+-ATPase, suggesting the involvement of retrograde
vesicular glutamate signaling. Transsynaptic regulation of PTP extends the repertoire
of synaptic computations, implementing a brake on mossy fiber detonation and a
“smart teacher” function of hippocampal mossy fiber synapses.
acknowledged_ssus:
- _id: SSU
acknowledgement: We thank Drs. Carolina Borges-Merjane and Jose Guzman for critically
reading the manuscript, and Pablo Castillo for discussions. We are grateful to Alois
Schlögl for help with analysis, Florian Marr for excellent technical assistance
and cell reconstruction, Christina Altmutter for technical help, Eleftheria Kralli-Beller
for manuscript editing, and the Scientific Service Units of IST Austria for support.
This project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation program (grant agreement No
692692) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27,
Wittgenstein award), both to P.J.
article_number: '2912'
article_processing_charge: Yes
article_type: original
author:
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Yuji
full_name: Okamoto, Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vandael DH, Okamoto Y, Jonas PM. Transsynaptic modulation of presynaptic short-term
plasticity in hippocampal mossy fiber synapses. Nature Communications.
2021;12(1). doi:10.1038/s41467-021-23153-5
apa: Vandael, D. H., Okamoto, Y., & Jonas, P. M. (2021). Transsynaptic modulation
of presynaptic short-term plasticity in hippocampal mossy fiber synapses. Nature
Communications. Springer. https://doi.org/10.1038/s41467-021-23153-5
chicago: Vandael, David H, Yuji Okamoto, and Peter M Jonas. “Transsynaptic Modulation
of Presynaptic Short-Term Plasticity in Hippocampal Mossy Fiber Synapses.” Nature
Communications. Springer, 2021. https://doi.org/10.1038/s41467-021-23153-5.
ieee: D. H. Vandael, Y. Okamoto, and P. M. Jonas, “Transsynaptic modulation of presynaptic
short-term plasticity in hippocampal mossy fiber synapses,” Nature Communications,
vol. 12, no. 1. Springer, 2021.
ista: Vandael DH, Okamoto Y, Jonas PM. 2021. Transsynaptic modulation of presynaptic
short-term plasticity in hippocampal mossy fiber synapses. Nature Communications.
12(1), 2912.
mla: Vandael, David H., et al. “Transsynaptic Modulation of Presynaptic Short-Term
Plasticity in Hippocampal Mossy Fiber Synapses.” Nature Communications,
vol. 12, no. 1, 2912, Springer, 2021, doi:10.1038/s41467-021-23153-5.
short: D.H. Vandael, Y. Okamoto, P.M. Jonas, Nature Communications 12 (2021).
corr_author: '1'
date_created: 2021-08-06T07:22:55Z
date_published: 2021-05-18T00:00:00Z
date_updated: 2025-06-12T06:28:45Z
day: '18'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41467-021-23153-5
ec_funded: 1
external_id:
isi:
- '000655481800014'
pmid:
- '34006874'
file:
- access_level: open_access
checksum: 6036a8cdae95e1707c2a04d54e325ff4
content_type: application/pdf
creator: kschuh
date_created: 2021-12-17T11:34:50Z
date_updated: 2021-12-17T11:34:50Z
file_id: '10563'
file_name: 2021_NatureCommunications_Vandael.pdf
file_size: 3108845
relation: main_file
success: 1
file_date_updated: 2021-12-17T11:34:50Z
fulldoi: https://doi.org/10.1038/s41467-021-23153-5
has_accepted_license: '1'
intvolume: ' 12'
isi: 1
issue: '1'
keyword:
- general physics and astronomy
- general biochemistry
- genetics and molecular biology
- general chemistry
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
publication: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/synaptic-transmission-not-a-one-way-street/
scopus_import: '1'
status: public
title: Transsynaptic modulation of presynaptic short-term plasticity in hippocampal
mossy fiber synapses
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2021'
...
---
_id: '9438'
abstract:
- lang: eng
text: Rigorous investigation of synaptic transmission requires analysis of unitary
synaptic events by simultaneous recording from presynaptic terminals and postsynaptic
target neurons. However, this has been achieved at only a limited number of model
synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical
presynaptic terminals have been largely inaccessible to direct presynaptic recording,
due to their small size. Here, we describe a protocol for improved subcellular
patch-clamp recording in rat and mouse brain slices, with the synapse in a largely
intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc
morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals
are stimulated minimally invasively in the bouton-attached configuration, in which
the cytoplasmic content remains unperturbed, or in the whole-bouton configuration,
in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic
recordings can be integrated with biocytin labeling and morphological analysis,
allowing correlative investigation of synapse structure and function. Paired recordings
can be obtained from mossy fiber terminals in slices from both rats and mice,
implying applicability to genetically modified synapses. Paired recordings can
also be performed together with axon tract stimulation or optogenetic activation,
allowing comparison of unitary and compound synaptic events in the same target
cell. Finally, paired recordings can be combined with spontaneous event analysis,
permitting collection of miniature events generated at a single identified synapse.
In conclusion, the subcellular patch-clamp techniques detailed here should facilitate
analysis of biophysics, plasticity and circuit function of cortical synapses in
the mammalian central nervous system.
acknowledged_ssus:
- _id: M-Shop
acknowledgement: This project received funding from the European Research Council
(ERC) under the European Union’s Horizon 2020 research and innovation programme
(grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful
to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction,
E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST
Austria, especially T. Asenov and Miba machine shop, for maximally efficient support.
article_processing_charge: No
article_type: original
author:
- first_name: David H
full_name: Vandael, David H
id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
last_name: Vandael
orcid: 0000-0001-7577-1676
- first_name: Yuji
full_name: Okamoto, Yuji
id: 3337E116-F248-11E8-B48F-1D18A9856A87
last_name: Okamoto
orcid: 0000-0003-0408-6094
- first_name: Carolina
full_name: Borges Merjane, Carolina
id: 4305C450-F248-11E8-B48F-1D18A9856A87
last_name: Borges Merjane
orcid: 0000-0003-0005-401X
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Benjamin
full_name: Suter, Benjamin
id: 4952F31E-F248-11E8-B48F-1D18A9856A87
last_name: Suter
orcid: 0000-0002-9885-6936
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
pre- and postsynaptic recording at cortical synapses. Nature Protocols.
2021;16(6):2947–2967. doi:10.1038/s41596-021-00526-0
apa: Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter,
B., & Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton
stimulation and simultaneous pre- and postsynaptic recording at cortical synapses.
Nature Protocols. Springer Nature. https://doi.org/10.1038/s41596-021-00526-0
chicago: Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas
Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques
for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording
at Cortical Synapses.” Nature Protocols. Springer Nature, 2021. https://doi.org/10.1038/s41596-021-00526-0.
ieee: D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter,
and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation
and simultaneous pre- and postsynaptic recording at cortical synapses,” Nature
Protocols, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.
ista: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and
simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols.
16(6), 2947–2967.
mla: Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton
Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.”
Nature Protocols, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967,
doi:10.1038/s41596-021-00526-0.
short: D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter,
P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.
corr_author: '1'
date_created: 2021-05-30T22:01:24Z
date_published: 2021-06-01T00:00:00Z
date_updated: 2025-04-22T22:30:43Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41596-021-00526-0
ec_funded: 1
external_id:
isi:
- '000650528700003'
pmid:
- '33990799'
file:
- access_level: open_access
checksum: 7eb580abd8893cdb0b410cf41bc8c263
content_type: application/pdf
creator: cziletti
date_created: 2021-07-08T12:27:55Z
date_updated: 2021-12-02T23:30:05Z
embargo: 2021-12-01
file_id: '9639'
file_name: VandaeletalAuthorVersion2021.pdf
file_size: 38574802
relation: main_file
file_date_updated: 2021-12-02T23:30:05Z
fulldoi: https://doi.org/10.1038/s41596-021-00526-0
has_accepted_license: '1'
intvolume: ' 16'
isi: 1
issue: '6'
language:
- iso: eng
month: '06'
oa: 1
oa_version: Submitted Version
page: 2947–2967
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z00312
name: Synaptic communication in neuronal microcircuits
- _id: 2696E7FE-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: V00739
name: Structural plasticity at mossy fiber-CA3 synapses
publication: Nature Protocols
publication_identifier:
eissn:
- 1750-2799
issn:
- 1754-2189
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
pre- and postsynaptic recording at cortical synapses
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2021'
...
---
OA_place: repository
OA_type: green
_id: '10816'
abstract:
- lang: eng
text: Pattern separation is a fundamental brain computation that converts small
differences in input patterns into large differences in output patterns. Several
synaptic mechanisms of pattern separation have been proposed, including code expansion,
inhibition and plasticity; however, which of these mechanisms play a role in the
entorhinal cortex (EC)–dentate gyrus (DG)–CA3 circuit, a classical pattern separation
circuit, remains unclear. Here we show that a biologically realistic, full-scale
EC–DG–CA3 circuit model, including granule cells (GCs) and parvalbumin-positive
inhibitory interneurons (PV+-INs) in the DG, is an efficient pattern separator.
Both external gamma-modulated inhibition and internal lateral inhibition mediated
by PV+-INs substantially contributed to pattern separation. Both local connectivity
and fast signaling at GC–PV+-IN synapses were important for maximum effectiveness.
Similarly, mossy fiber synapses with conditional detonator properties contributed
to pattern separation. By contrast, perforant path synapses with Hebbian synaptic
plasticity and direct EC–CA3 connection shifted the network towards pattern completion.
Our results demonstrate that the specific properties of cells and synapses optimize
higher-order computations in biological networks and might be useful to improve
the deep learning capabilities of technical networks.
acknowledged_ssus:
- _id: SSU
acknowledgement: We thank A. Aertsen, N. Kopell, W. Maass, A. Roth, F. Stella and
T. Vogels for critically reading earlier versions of the manuscript. We are grateful
to F. Marr and C. Altmutter for excellent technical assistance, E. Kralli-Beller
for manuscript editing, and the Scientific Service Units of IST Austria for efficient
support. Finally, we thank T. Carnevale, L. Erdös, M. Hines, D. Nykamp and D. Schröder
for useful discussions, and R. Friedrich and S. Wiechert for sharing unpublished
data. This project received funding from the European Research Council (ERC) under
the European Union’s Horizon 2020 research and innovation programme (grant agreement
no. 692692, P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z
312-B27, Wittgenstein award to P.J. and P 31815 to S.J.G.).
article_processing_charge: No
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author:
- first_name: José
full_name: Guzmán, José
id: 30CC5506-F248-11E8-B48F-1D18A9856A87
last_name: Guzmán
orcid: 0000-0003-2209-5242
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: 'Claudia '
full_name: 'Espinoza Martinez, Claudia '
id: 31FFEE2E-F248-11E8-B48F-1D18A9856A87
last_name: Espinoza Martinez
orcid: 0000-0003-4710-2082
- first_name: Xiaomin
full_name: Zhang, Xiaomin
id: 423EC9C2-F248-11E8-B48F-1D18A9856A87
last_name: Zhang
orcid: 0000-0003-0256-6529
- first_name: Benjamin
full_name: Suter, Benjamin
id: 4952F31E-F248-11E8-B48F-1D18A9856A87
last_name: Suter
orcid: 0000-0002-9885-6936
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
biorxivid: 1
citation:
ama: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. How connectivity
rules and synaptic properties shape the efficacy of pattern separation in the
entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science.
2021;1(12):830-842. doi:10.1038/s43588-021-00157-1
apa: Guzmán, J., Schlögl, A., Espinoza Martinez, C., Zhang, X., Suter, B., &
Jonas, P. M. (2021). How connectivity rules and synaptic properties shape the
efficacy of pattern separation in the entorhinal cortex–dentate gyrus–CA3 network.
Nature Computational Science. Springer Nature. https://doi.org/10.1038/s43588-021-00157-1
chicago: Guzmán, José, Alois Schlögl, Claudia Espinoza Martinez, Xiaomin Zhang,
Benjamin Suter, and Peter M Jonas. “How Connectivity Rules and Synaptic Properties
Shape the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
Network.” Nature Computational Science. Springer Nature, 2021. https://doi.org/10.1038/s43588-021-00157-1.
ieee: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, and P. M.
Jonas, “How connectivity rules and synaptic properties shape the efficacy of pattern
separation in the entorhinal cortex–dentate gyrus–CA3 network,” Nature Computational
Science, vol. 1, no. 12. Springer Nature, pp. 830–842, 2021.
ista: Guzmán J, Schlögl A, Espinoza Martinez C, Zhang X, Suter B, Jonas PM. 2021.
How connectivity rules and synaptic properties shape the efficacy of pattern separation
in the entorhinal cortex–dentate gyrus–CA3 network. Nature Computational Science.
1(12), 830–842.
mla: Guzmán, José, et al. “How Connectivity Rules and Synaptic Properties Shape
the Efficacy of Pattern Separation in the Entorhinal Cortex–Dentate Gyrus–CA3
Network.” Nature Computational Science, vol. 1, no. 12, Springer Nature,
2021, pp. 830–42, doi:10.1038/s43588-021-00157-1.
short: J. Guzmán, A. Schlögl, C. Espinoza Martinez, X. Zhang, B. Suter, P.M. Jonas,
Nature Computational Science 1 (2021) 830–842.
corr_author: '1'
date_created: 2022-03-04T08:32:36Z
date_published: 2021-12-16T00:00:00Z
date_updated: 2026-07-28T12:15:17Z
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doi: 10.1038/s43588-021-00157-1
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title: How connectivity rules and synaptic properties shape the efficacy of pattern
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