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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
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doi: 10.1038/s41467-026-71914-x
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apa: Schlögl, A. (2026). CA3Simu v1.06 (vargas2026v1). Institute of Science and
Technology Austria. https://doi.org/10.15479/AT-ISTA-21442
chicago: Schlögl, Alois. “CA3Simu v1.06 (Vargas2026v1).” Institute of Science and
Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-21442.
ieee: A. Schlögl, “CA3Simu v1.06 (vargas2026v1).” Institute of Science and Technology
Austria, 2026.
ista: Schlögl A. 2026. CA3Simu v1.06 (vargas2026v1), Institute of Science and Technology
Austria, 10.15479/AT-ISTA-21442.
mla: Schlögl, Alois. CA3Simu v1.06 (Vargas2026v1). Institute of Science and
Technology Austria, 2026, doi:10.15479/AT-ISTA-21442.
short: A. Schlögl, (2026).
corr_author: '1'
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keyword:
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- ca3 simulations
- modelling
license: https://opensource.org/licenses/GPL-3.0
month: '03'
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project:
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grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
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name: Biophysics and circuit function of a giant cortical glutamatergic synapse
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title: CA3Simu v1.06 (vargas2026v1)
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acknowledgement: "This project was supported by the following funding agencies: ERC
under the European\r\nUnion's Horizon 2020 research and innovation program (ERC
Advanced Grants No 692692\r\n“GIANTSYN” and 101199096 “CA3-SYNGRAM” to P.J.), the
Fonds zur Förderung der\r\nwissenschaftlichen Forschung (P 36232-B, stand-alone
grant, PAT 4178023, principal\r\ninvestigator project, and 10.55776/CoE 16 “GABA
neurons” to P.J.), and the European Union’s\r\nHorizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant\r\nagreement (No 101034413, to
K.L.)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
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full_name: Lin, Peipeng
id: 7E3060D0-A92C-11E9-A326-26C8E5697425
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citation:
ama: 'Lin P. Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses. 2026. doi:10.15479/AT-ISTA-22735'
apa: 'Lin, P. (2026). Calibrating the teacher synapse: Mechanisms and functional
significance of presynaptic inhibition at hippocampal mossy fiber synapses.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-22735'
chicago: 'Lin, Peipeng. “Calibrating the Teacher Synapse: Mechanisms and Functional
Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.” Institute
of Science and Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-22735.'
ieee: 'P. Lin, “Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses,” Institute of Science
and Technology Austria, 2026.'
ista: 'Lin P. 2026. Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses. Institute of Science
and Technology Austria.'
mla: 'Lin, Peipeng. Calibrating the Teacher Synapse: Mechanisms and Functional
Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.
Institute of Science and Technology Austria, 2026, doi:10.15479/AT-ISTA-22735.'
short: 'P. Lin, Calibrating the Teacher Synapse: Mechanisms and Functional Significance
of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses, Institute of Science
and Technology Austria, 2026.'
corr_author: '1'
das_tickbox: '0'
date_created: 2026-08-18T15:23:41Z
date_published: 2026-08-25T00:00:00Z
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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
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grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
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name: Synaptic networks of human brain
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issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
researchdata_availability: upon request
status: public
supervisor:
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
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apa: Jamrichova, S. (2026). Timing and strength of synaptic transmission at hippocampal
mossy fiber synapses in mice and humans. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT-ISTA-22775
chicago: Jamrichova, Silvia. “Timing and Strength of Synaptic Transmission at Hippocampal
Mossy Fiber Synapses in Mice and Humans.” Institute of Science and Technology
Austria, 2026. https://doi.org/10.15479/AT-ISTA-22775.
ieee: S. Jamrichova, “Timing and strength of synaptic transmission at hippocampal
mossy fiber synapses in mice and humans,” Institute of Science and Technology
Austria, 2026.
ista: Jamrichova S. 2026. Timing and strength of synaptic transmission at hippocampal
mossy fiber synapses in mice and humans. Institute of Science and Technology Austria.
mla: Jamrichova, Silvia. Timing and Strength of Synaptic Transmission at Hippocampal
Mossy Fiber Synapses in Mice and Humans. Institute of Science and Technology
Austria, 2026, doi:10.15479/AT-ISTA-22775.
short: S. Jamrichova, Timing and Strength of Synaptic Transmission at Hippocampal
Mossy Fiber Synapses in Mice and Humans, Institute of Science and Technology Austria,
2026.
corr_author: '1'
date_created: 2026-09-03T08:06:58Z
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page: '153'
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: e62b56fe-ab3c-11f0-94c7-d181dd352b3b
grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
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grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
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name: Synaptic networks of human brain
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publication_identifier:
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issn:
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publication_status: published
publisher: Institute of Science and Technology Austria
researchdata_availability: upon request
status: public
supervisor:
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
supplementarymaterial: no
title: Timing and strength of synaptic transmission at hippocampal mossy fiber synapses
in mice and humans
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...
---
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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
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.celrep.2025.116080
ec_funded: 1
external_id:
isi:
- '001544472300002'
file:
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checksum: 556ff9760661ecd23949d75031043b1f
content_type: application/pdf
creator: dernst
date_created: 2025-08-04T06:53:07Z
date_updated: 2025-08-04T06:53:07Z
file_id: '20106'
file_name: 2025_CellReports_Watson.pdf
file_size: 27695214
relation: main_file
success: 1
file_date_updated: 2025-08-04T06:53:07Z
fulldoi: https://doi.org/10.1016/j.celrep.2025.116080
has_accepted_license: '1'
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
DOAJ_listed: '1'
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
date_created: 2024-12-03T08:56:53Z
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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:
- _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: b1b85715-d554-11ed-a5ad-84a07fc9f18e
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:
- 1544-9173
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '18296'
relation: research_data
status: public
scopus_import: '1'
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: 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
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publication: Neuron
publication_identifier:
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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)
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...
---
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abstract:
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text: "The coupling between presynaptic Ca2+ channels and release sensors is a key
factor that\r\ndetermines speed and efficacy of synapse transmission. At some
excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development,
and tightening is often\r\nassociated with a switch in the reliance on different
Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains
unknown, and it is unclear how it changes\r\nduring development. To address this
question, we analyzed the coupling configuration at the\r\ncerebellar basket cell
(BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining
biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of
BC–PC indicated that release probability decreased, while the\r\nnumber of functional
sites increased during development. Although transmitter release\r\npersistently
relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof
the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring
development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic
action potentials became shorter during development, suggesting reduced\r\nefficacy
of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica
labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic
P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas
docked vesicles were only clustered at later\r\ndevelopmental stages. The number
of functional release sites correlated better with the AZ\r\nnumber early in development,
but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling
suggested a developmental transformation from a more random to a more\r\nclustered
coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na
point-to-point configuration, optimizing speed, reliability, and energy efficiency
of synaptic\r\ntransmission."
acknowledged_ssus:
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alternative_title:
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author:
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full_name: Chen, JingJing
id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
last_name: Chen
citation:
ama: Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels
and release sensors at a central GABAergic synapse. 2024. doi:10.15479/at:ista:15101
apa: Chen, J. (2024). Developmental transformation of nanodomain coupling between
Ca2+ channels and release sensors at a central GABAergic synapse. Institute
of Science and Technology Austria. https://doi.org/10.15479/at:ista:15101
chicago: Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between
Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of
Science and Technology Austria, 2024. https://doi.org/10.15479/at:ista:15101.
ieee: J. Chen, “Developmental transformation of nanodomain coupling between Ca2+
channels and release sensors at a central GABAergic synapse,” Institute of Science
and Technology Austria, 2024.
ista: Chen J. 2024. Developmental transformation of nanodomain coupling between
Ca2+ channels and release sensors at a central GABAergic synapse. Institute of
Science and Technology Austria.
mla: Chen, JingJing. Developmental Transformation of Nanodomain Coupling between
Ca2+ Channels and Release Sensors at a Central GABAergic Synapse. Institute
of Science and Technology Austria, 2024, doi:10.15479/at:ista:15101.
short: J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+
Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science
and Technology Austria, 2024.
corr_author: '1'
das_tickbox: '0'
date_created: 2024-03-11T10:09:54Z
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supervisor:
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orcid: 0000-0001-5001-4804
supplementarymaterial: no
title: Developmental transformation of nanodomain coupling between Ca2+ channels and
release sensors at a central GABAergic synapse
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...