---
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'
file:
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checksum: d0b0093493926985b4c268662ff4d556
content_type: application/pdf
creator: dernst
date_created: 2026-07-01T06:46:06Z
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intvolume: ' 17'
language:
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month: '06'
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: 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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relation: research_data
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researchdata_availability: yes
scopus_import: '1'
status: public
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_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. Elsevier. 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. Elsevier, 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. Elsevier,
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, Elsevier,
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: 2026-04-14T08:34:32Z
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:
- access_level: open_access
checksum: d5a818edc32d249cdf75e1bb5b70a4b7
content_type: application/pdf
creator: dernst
date_created: 2025-01-27T08:46:33Z
date_updated: 2025-01-27T08:46:33Z
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success: 1
file_date_updated: 2025-01-27T08:46:33Z
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intvolume: ' 188'
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issue: '2'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 501-514.e18
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: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
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
- _id: 9B861AAC-BA93-11EA-9121-9846C619BF3A
name: NOMIS Fellowship Program
publication: Cell
publication_identifier:
eissn:
- 1097-4172
issn:
- 0092-8674
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
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status: public
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)
short: CC BY (4.0)
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. Elsevier.
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.
Elsevier, 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.
Elsevier, 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, Elsevier, 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: 2025-09-30T14:12:02Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1016/j.celrep.2025.116080
ec_funded: 1
external_id:
isi:
- '001544472300002'
file:
- access_level: open_access
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
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
publication: Cell Reports
publication_identifier:
eissn:
- 2211-1247
issn:
- 2639-1856
publication_status: published
publisher: Elsevier
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: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 44
year: '2025'
...
---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20457'
abstract:
- lang: eng
text: Patch-clamp recording of miniature postsynaptic currents (mPSCs, or ‘minis’)
is used extensively to investigate the functional properties of synapses. With
this approach, spontaneous synaptic transmission events are recorded in an attempt
to determine quantal synaptic parameters or the effect of synaptic manipulations.
However, at the majority of brain synapses these events are small, with many undetectable
due to recording noise. The effects of incomplete detection were well appreciated
in the early years of synaptic physiology analysis, but appear to be increasingly
forgotten. Here we sought to characterise the consequences of incomplete detection
on the interpretability of mini analysis, using simulated mPSC data to give full
control over event parameters. We demonstrate that commonly reported measures
such as mean event amplitude and frequency, are misrepresented by the loss of
undetected events. Probabilistic loss of small events results in detected event
amplitude distributions that appear biologically complete, yet do not reflect
the underlying synaptic properties. With both simulated and experimental datasets,
we demonstrate that specific changes in event amplitude are primarily detected
as changes in frequency, compromising classical biological interpretations. To
facilitate more robust data analysis and interpretation, we detail a means for
experimental estimation of the event detection limit and provide practical recommendations
for data analysis. Together, our study highlights how mini analysis is prone to
falsely reporting synaptic changes, raising awareness of these considerations,
and provides a framework for more robust data analysis and interpretation.
acknowledgement: This work was supported by Biological Services teams at both the
Laboratory of Molecular Biology and Ares facilities. The authors are very grateful
to Prof. Helmut Kessels and Dr. Hinze Ho for initial discussions that led to this
study, Dr. Andrew Penn for constructive feedback on the project, Xinyao Dou for
comments on the study, and Profs. Peter Jonas and Roger Nicoll for feedback on the
manuscript. Funding was provided by the Medical Research Council (MRC – MC_U105174197
to I.H.G.) and the European Union's Horizon 2020 programme through a Marie Skłodowska-Curie
Actions Individual Fellowship (MSCA-IF 101026635 to J.F.W.).
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
citation:
ama: Greger IH, Watson J. ‘Mini analysis’ misrepresents changes in synaptic properties
due to incomplete event detection. Journal of Physiology. 2025;603(22):7189-7205.
doi:10.1113/JP288183
apa: Greger, I. H., & Watson, J. (2025). ‘Mini analysis’ misrepresents changes
in synaptic properties due to incomplete event detection. Journal of Physiology.
Wiley. https://doi.org/10.1113/JP288183
chicago: Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes
in Synaptic Properties Due to Incomplete Event Detection.” Journal of Physiology.
Wiley, 2025. https://doi.org/10.1113/JP288183.
ieee: I. H. Greger and J. Watson, “‘Mini analysis’ misrepresents changes in synaptic
properties due to incomplete event detection,” Journal of Physiology, vol.
603, no. 22. Wiley, pp. 7189–7205, 2025.
ista: Greger IH, Watson J. 2025. ‘Mini analysis’ misrepresents changes in synaptic
properties due to incomplete event detection. Journal of Physiology. 603(22),
7189–7205.
mla: Greger, Ingo H., and Jake Watson. “‘Mini Analysis’ Misrepresents Changes in
Synaptic Properties Due to Incomplete Event Detection.” Journal of Physiology,
vol. 603, no. 22, Wiley, 2025, pp. 7189–205, doi:10.1113/JP288183.
short: I.H. Greger, J. Watson, Journal of Physiology 603 (2025) 7189–7205.
corr_author: '1'
date_created: 2025-10-12T22:01:27Z
date_published: 2025-11-15T00:00:00Z
date_updated: 2026-01-05T13:13:32Z
day: '15'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1113/JP288183
ec_funded: 1
external_id:
isi:
- '001581924700001'
pmid:
- '41015537'
file:
- access_level: open_access
checksum: 3326e49795f44a7c51c16ecbcce58cde
content_type: application/pdf
creator: dernst
date_created: 2026-01-05T13:13:06Z
date_updated: 2026-01-05T13:13:06Z
file_id: '20949'
file_name: 2025_JourPhysiology_Greger.pdf
file_size: 10875254
relation: main_file
success: 1
file_date_updated: 2026-01-05T13:13:06Z
has_accepted_license: '1'
intvolume: ' 603'
isi: 1
issue: '22'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
page: 7189-7205
pmid: 1
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
publication: Journal of Physiology
publication_identifier:
eissn:
- 1469-7793
issn:
- 0022-3751
publication_status: published
publisher: Wiley
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/jakefwatson/miniplace
scopus_import: '1'
status: public
title: ‘Mini analysis’ misrepresents changes in synaptic properties due to incomplete
event detection
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: 603
year: '2025'
...
---
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'
date_created: 2023-09-03T22:01:15Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2026-04-14T08:34:35Z
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:
- access_level: open_access
checksum: 57d5fafb16f02dcb9f7dddb1bd7e2a71
content_type: application/pdf
creator: dernst
date_created: 2025-01-09T07:48:01Z
date_updated: 2025-01-09T07:48:01Z
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
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
scopus_import: '1'
status: public
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 42
year: '2024'
...
---
OA_place: publisher
OA_type: hybrid
_id: '15379'
abstract:
- lang: eng
text: Long-term potentiation (LTP) of excitatory synapses is a leading model to
explain the concept of information storage in the brain. Multiple mechanisms contribute
to LTP, but central amongst them is an increased sensitivity of the postsynaptic
membrane to neurotransmitter release. This sensitivity is predominantly determined
by the abundance and localization of AMPA-type glutamate receptors (AMPARs). A
combination of AMPAR structural data, super-resolution imaging of excitatory synapses,
and an abundance of electrophysiological studies are providing an ever-clearer
picture of how AMPARs are recruited and organized at synaptic junctions. Here,
we review the latest insights into this process, and discuss how both cytoplasmic
and extracellular receptor elements cooperate to tune the AMPAR response at the
hippocampal CA1 synapse.
acknowledgement: The authors thank Alexander Scrutton and James M. Krieger for comments
on the manuscript. The authors also acknowledge Shraddha Nayak for help with Figure
1B design. This work was supported by grants from the Medical Research Council (MC_U105174197),
the BBSRC (BB/N002113/1), and the Wellcome Trust (223194/Z/21/Z) to IHG.
article_number: ' 2400006'
article_processing_charge: Yes (in subscription journal)
article_type: review
author:
- first_name: Imogen
full_name: Stockwell, Imogen
last_name: Stockwell
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
citation:
ama: Stockwell I, Watson J, Greger IH. Tuning synaptic strength by regulation of
AMPA glutamate receptor localization. BioEssays. 2024;46(7). doi:10.1002/bies.202400006
apa: Stockwell, I., Watson, J., & Greger, I. H. (2024). Tuning synaptic strength
by regulation of AMPA glutamate receptor localization. BioEssays. Wiley.
https://doi.org/10.1002/bies.202400006
chicago: Stockwell, Imogen, Jake Watson, and Ingo H. Greger. “Tuning Synaptic Strength
by Regulation of AMPA Glutamate Receptor Localization.” BioEssays. Wiley,
2024. https://doi.org/10.1002/bies.202400006.
ieee: I. Stockwell, J. Watson, and I. H. Greger, “Tuning synaptic strength by regulation
of AMPA glutamate receptor localization,” BioEssays, vol. 46, no. 7. Wiley,
2024.
ista: Stockwell I, Watson J, Greger IH. 2024. Tuning synaptic strength by regulation
of AMPA glutamate receptor localization. BioEssays. 46(7), 2400006.
mla: Stockwell, Imogen, et al. “Tuning Synaptic Strength by Regulation of AMPA Glutamate
Receptor Localization.” BioEssays, vol. 46, no. 7, 2400006, Wiley, 2024,
doi:10.1002/bies.202400006.
short: I. Stockwell, J. Watson, I.H. Greger, BioEssays 46 (2024).
date_created: 2024-05-12T22:01:02Z
date_published: 2024-07-01T00:00:00Z
date_updated: 2025-09-08T07:25:02Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1002/bies.202400006
external_id:
isi:
- '001214545700001'
pmid:
- '38693811'
file:
- access_level: open_access
checksum: dc8be74156657e8aab12a9d613233ee3
content_type: application/pdf
creator: dernst
date_created: 2025-01-09T09:31:05Z
date_updated: 2025-01-09T09:31:05Z
file_id: '18801'
file_name: 2024_BioEssays_Stockwell.pdf
file_size: 775825
relation: main_file
success: 1
file_date_updated: 2025-01-09T09:31:05Z
has_accepted_license: '1'
intvolume: ' 46'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: BioEssays
publication_identifier:
eissn:
- 1521-1878
issn:
- 0265-9247
publication_status: published
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: Tuning synaptic strength by regulation of AMPA glutamate receptor localization
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: 46
year: '2024'
...
---
_id: '18058'
abstract:
- lang: eng
text: DNA cloning is a core technique in biomedical and biotechnological research
and is used to assemble and modify DNA fragments at will. While DNA cloning has
traditionally relied on restriction enzymes, recent homology-based methods offer
improved protocols together with seamless and directional assembly of desired
products, overcoming the main disadvantages of restriction enzyme DNA cloning.
This chapter provides a historical perspective on DNA cloning, presents a detailed
discussion on state-of-the-art in vitro and in vivo homology-based methodologies,
covering the basics of how to perform all major plasmid modifications (sub-cloning,
site-directed mutagenesis, insertions, and deletions), and gives examples of how
to apply these techniques for complex DNA cloning projects.
article_processing_charge: No
author:
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Sandra
full_name: Arroyo-Urea, Sandra
last_name: Arroyo-Urea
- first_name: Javier
full_name: García-Nafría, Javier
last_name: García-Nafría
citation:
ama: 'Watson J, Arroyo-Urea S, García-Nafría J. DNA Cloning. In: Liu D, ed. Handbook
of Molecular Biotechnology. 1st ed. Boca Raton: CRC Press; 2024:66-72. doi:10.1201/9781003055211-8'
apa: 'Watson, J., Arroyo-Urea, S., & García-Nafría, J. (2024). DNA Cloning.
In D. Liu (Ed.), Handbook of Molecular Biotechnology (1st ed., pp. 66–72).
Boca Raton: CRC Press. https://doi.org/10.1201/9781003055211-8'
chicago: 'Watson, Jake, Sandra Arroyo-Urea, and Javier García-Nafría. “DNA Cloning.”
In Handbook of Molecular Biotechnology, edited by Dongyou Liu, 1st ed.,
66–72. Boca Raton: CRC Press, 2024. https://doi.org/10.1201/9781003055211-8.'
ieee: 'J. Watson, S. Arroyo-Urea, and J. García-Nafría, “DNA Cloning,” in Handbook
of Molecular Biotechnology, 1st ed., D. Liu, Ed. Boca Raton: CRC Press, 2024,
pp. 66–72.'
ista: 'Watson J, Arroyo-Urea S, García-Nafría J. 2024.DNA Cloning. In: Handbook
of Molecular Biotechnology. , 66–72.'
mla: Watson, Jake, et al. “DNA Cloning.” Handbook of Molecular Biotechnology,
edited by Dongyou Liu, 1st ed., CRC Press, 2024, pp. 66–72, doi:10.1201/9781003055211-8.
short: J. Watson, S. Arroyo-Urea, J. García-Nafría, in:, D. Liu (Ed.), Handbook
of Molecular Biotechnology, 1st ed., CRC Press, Boca Raton, 2024, pp. 66–72.
date_created: 2024-09-11T10:40:36Z
date_published: 2024-09-05T00:00:00Z
date_updated: 2024-09-11T11:16:58Z
day: '05'
department:
- _id: PeJo
doi: 10.1201/9781003055211-8
edition: '1'
editor:
- first_name: Dongyou
full_name: Liu, Dongyou
last_name: Liu
language:
- iso: eng
month: '09'
oa_version: None
page: 66-72
place: Boca Raton
publication: Handbook of Molecular Biotechnology
publication_identifier:
eisbn:
- '9781003055211'
publication_status: published
publisher: CRC Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: DNA Cloning
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...
---
OA_place: repository
OA_type: green
_id: '12720'
abstract:
- lang: eng
text: Here we describe the in vivo DNA assembly approach, where molecular cloning
procedures are performed using an E. coli recA-independent recombination pathway,
which assembles linear fragments of DNA with short homologous termini. This pathway
is present in all standard laboratory E. coli strains and, by bypassing the need
for in vitro DNA assembly, allows simplified molecular cloning to be performed
without the plasmid instability issues associated with specialized recombination-cloning
bacterial strains. The methodology requires specific primer design and can perform
all standard plasmid modifications (insertions, deletions, mutagenesis, and sub-cloning)
in a rapid, simple, and cost-efficient manner, as it does not require commercial
kits or specialized bacterial strains. Additionally, this approach can be used
to perform complex procedures such as multiple modifications to a plasmid, as
up to 6 linear fragments can be assembled in vivo by this recombination pathway.
Procedures generally require less than 3 h, involving PCR amplification, DpnI
digestion of template DNA, and transformation, upon which circular plasmids are
assembled. In this chapter we describe the requirements, procedure, and potential
pitfalls when using this technique, as well as protocol variations to overcome
the most common issues.
alternative_title:
- Methods in Molecular Biology
article_processing_charge: No
author:
- first_name: Sandra
full_name: Arroyo-Urea, Sandra
last_name: Arroyo-Urea
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Javier
full_name: García-Nafría, Javier
last_name: García-Nafría
citation:
ama: 'Arroyo-Urea S, Watson J, García-Nafría J. Molecular Cloning Using In Vivo
DNA Assembly. In: Scarlett G, ed. DNA Manipulation and Analysis. Vol 2633.
MIMB. New York, NY, United States: Springer Nature; 2023:33-44. doi:10.1007/978-1-0716-3004-4_3'
apa: 'Arroyo-Urea, S., Watson, J., & García-Nafría, J. (2023). Molecular Cloning
Using In Vivo DNA Assembly. In G. Scarlett (Ed.), DNA Manipulation and Analysis
(Vol. 2633, pp. 33–44). New York, NY, United States: Springer Nature. https://doi.org/10.1007/978-1-0716-3004-4_3'
chicago: 'Arroyo-Urea, Sandra, Jake Watson, and Javier García-Nafría. “Molecular
Cloning Using In Vivo DNA Assembly.” In DNA Manipulation and Analysis,
edited by Garry Scarlett, 2633:33–44. MIMB. New York, NY, United States: Springer
Nature, 2023. https://doi.org/10.1007/978-1-0716-3004-4_3.'
ieee: 'S. Arroyo-Urea, J. Watson, and J. García-Nafría, “Molecular Cloning Using
In Vivo DNA Assembly,” in DNA Manipulation and Analysis, vol. 2633, G.
Scarlett, Ed. New York, NY, United States: Springer Nature, 2023, pp. 33–44.'
ista: 'Arroyo-Urea S, Watson J, García-Nafría J. 2023.Molecular Cloning Using In
Vivo DNA Assembly. In: DNA Manipulation and Analysis. Methods in Molecular Biology,
vol. 2633, 33–44.'
mla: Arroyo-Urea, Sandra, et al. “Molecular Cloning Using In Vivo DNA Assembly.”
DNA Manipulation and Analysis, edited by Garry Scarlett, vol. 2633, Springer
Nature, 2023, pp. 33–44, doi:10.1007/978-1-0716-3004-4_3.
short: S. Arroyo-Urea, J. Watson, J. García-Nafría, in:, G. Scarlett (Ed.), DNA
Manipulation and Analysis, Springer Nature, New York, NY, United States, 2023,
pp. 33–44.
date_created: 2023-03-12T23:01:02Z
date_published: 2023-03-01T00:00:00Z
date_updated: 2025-06-25T05:56:45Z
day: '01'
department:
- _id: PeJo
doi: 10.1007/978-1-0716-3004-4_3
editor:
- first_name: Garry
full_name: Scarlett, Garry
last_name: Scarlett
external_id:
pmid:
- '36853454'
intvolume: ' 2633'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://zaguan.unizar.es/record/125930/files/texto_completo.pdf
month: '03'
oa: 1
oa_version: Submitted Version
page: 33-44
place: New York, NY, United States
pmid: 1
publication: DNA Manipulation and Analysis
publication_identifier:
eisbn:
- 978-1-0716-3004-4
eissn:
- 1940-6029
isbn:
- 978-1-0716-3003-7
issn:
- 1064-3745
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
series_title: MIMB
status: public
title: Molecular Cloning Using In Vivo DNA Assembly
type: book_chapter
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 2633
year: '2023'
...
---
_id: '12786'
abstract:
- lang: eng
text: AMPA glutamate receptors (AMPARs) mediate excitatory neurotransmission throughout
the brain. Their signalling is uniquely diversified by brain region-specific auxiliary
subunits, providing an opportunity for the development of selective therapeutics.
AMPARs associated with TARP γ8 are enriched in the hippocampus, and are targets
of emerging anti-epileptic drugs. To understand their therapeutic activity, we
determined cryo-EM structures of the GluA1/2-γ8 receptor associated with three
potent, chemically diverse ligands. We find that despite sharing a lipid-exposed
and water-accessible binding pocket, drug action is differentially affected by
binding-site mutants. Together with patch-clamp recordings and MD simulations
we also demonstrate that ligand-triggered reorganisation of the AMPAR-TARP interface
contributes to modulation. Unexpectedly, one ligand (JNJ-61432059) acts bifunctionally,
negatively affecting GluA1 but exerting positive modulatory action on GluA2-containing
AMPARs, in a TARP stoichiometry-dependent manner. These results further illuminate
the action of TARPs, demonstrate the sensitive balance between positive and negative
modulatory action, and provide a mechanistic platform for development of both
positive and negative selective AMPAR modulators.
acknowledgement: We thank James Krieger for generating the ‘proDy’ interaction maps
in Fig. 5B and S7C, and Jan-Niklas Dohrke for critically reading the manuscript.
We thank members of the Greger lab for insightful comments during this study. We
acknowledge Trevor Rutherford for confirming ligand integrity by NMR. We are also
grateful to LMB scientific computing and the EM facility for their support. This
research was funded in part by the Wellcome Trust (223194/Z/21/Z) to I.H.G. For
the purpose of Open Access, the MRC Laboratory of Molecular Biology has applied
a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version
arising from this submission. Further funding came from the Medical Research Council
(MRU105174197) to I.H.G, and NIH grant (R56/R01MH123474) to T.N.
article_number: '1659'
article_processing_charge: No
article_type: original
author:
- first_name: Danyang
full_name: Zhang, Danyang
last_name: Zhang
- first_name: Remigijus
full_name: Lape, Remigijus
last_name: Lape
- first_name: Saher A.
full_name: Shaikh, Saher A.
last_name: Shaikh
- first_name: Bianka K.
full_name: Kohegyi, Bianka K.
last_name: Kohegyi
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Ondrej
full_name: Cais, Ondrej
last_name: Cais
- first_name: Terunaga
full_name: Nakagawa, Terunaga
last_name: Nakagawa
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
citation:
ama: Zhang D, Lape R, Shaikh SA, et al. Modulatory mechanisms of TARP γ8-selective
AMPA receptor therapeutics. Nature Communications. 2023;14. doi:10.1038/s41467-023-37259-5
apa: Zhang, D., Lape, R., Shaikh, S. A., Kohegyi, B. K., Watson, J., Cais, O., …
Greger, I. H. (2023). Modulatory mechanisms of TARP γ8-selective AMPA receptor
therapeutics. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-023-37259-5
chicago: Zhang, Danyang, Remigijus Lape, Saher A. Shaikh, Bianka K. Kohegyi, Jake
Watson, Ondrej Cais, Terunaga Nakagawa, and Ingo H. Greger. “Modulatory Mechanisms
of TARP Γ8-Selective AMPA Receptor Therapeutics.” Nature Communications.
Springer Nature, 2023. https://doi.org/10.1038/s41467-023-37259-5.
ieee: D. Zhang et al., “Modulatory mechanisms of TARP γ8-selective AMPA receptor
therapeutics,” Nature Communications, vol. 14. Springer Nature, 2023.
ista: Zhang D, Lape R, Shaikh SA, Kohegyi BK, Watson J, Cais O, Nakagawa T, Greger
IH. 2023. Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics.
Nature Communications. 14, 1659.
mla: Zhang, Danyang, et al. “Modulatory Mechanisms of TARP Γ8-Selective AMPA Receptor
Therapeutics.” Nature Communications, vol. 14, 1659, Springer Nature, 2023,
doi:10.1038/s41467-023-37259-5.
short: D. Zhang, R. Lape, S.A. Shaikh, B.K. Kohegyi, J. Watson, O. Cais, T. Nakagawa,
I.H. Greger, Nature Communications 14 (2023).
date_created: 2023-04-02T22:01:09Z
date_published: 2023-03-25T00:00:00Z
date_updated: 2023-12-13T11:15:58Z
day: '25'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41467-023-37259-5
external_id:
isi:
- '001066658700003'
file:
- access_level: open_access
checksum: 0a97b31191432dae5853bbb5ccb7698d
content_type: application/pdf
creator: dernst
date_created: 2023-04-03T06:38:56Z
date_updated: 2023-04-03T06:38:56Z
file_id: '12797'
file_name: 2023_NatureComm_Zhang.pdf
file_size: 2613996
relation: main_file
success: 1
file_date_updated: 2023-04-03T06:38:56Z
has_accepted_license: '1'
intvolume: ' 14'
isi: 1
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modulatory mechanisms of TARP γ8-selective AMPA receptor therapeutics
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: 14
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: 2026-07-06T12:49:46Z
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
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: '18674'
relation: dissertation_contains
status: public
- id: '11943'
relation: earlier_version
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: '10763'
abstract:
- lang: eng
text: "AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission
at excitatory\r\nsynapses in the brain. Glutamate binding to the receptor’s ligand-binding
domains (LBDs)\r\nleads to ion channel activation and desensitization. Gating
kinetics shape synaptic transmission\r\nand are strongly modulated by transmembrane
AMPAR regulatory proteins (TARPs)\r\nthrough currently incompletely resolved mechanisms.
Here, electron cryo-microscopy\r\nstructures of the GluA1/2 TARP-γ8 complex, in
both open and desensitized states\r\n(at 3.5 Å), reveal state-selective engagement
of the LBDs by the large TARP-γ8 loop (‘β1’),\r\nelucidating how this TARP stabilizes
specific gating states. We further show how TARPs alter\r\nchannel rectification,
by interacting with the pore helix of the selectivity filter. Lastly, we\r\nreveal
that the Q/R-editing site couples the channel constriction at the filter entrance
to the\r\ngate, and forms the major cation binding site in the conduction path.
Our results provide a\r\nmechanistic framework of how TARPs modulate AMPAR gating
and conductance."
acknowledgement: "We thank Ondrej Cais for critical reading of the manuscript. We
are grateful to LMB\r\nscientific computing and the EM facility for support, Paul
Emsley for help with model\r\nbuilding and Takanori Nakane for helpful comments
with Relion 3.1. This work was\r\nsupported by grants from the Medical Research
Council (MC_U105174197) and BBSRC\r\n(BB/N002113/1) to I.H.G, and grants from the
MCIN/AEI/ 10.13039/501100011033 and\r\n“ESF Investing in your future” to B.H (PID2019-106284GA-I00
and RYC2018-025720-I)."
article_number: '734'
article_processing_charge: No
article_type: original
author:
- first_name: Beatriz
full_name: Herguedas, Beatriz
last_name: Herguedas
- first_name: Bianka K.
full_name: Kohegyi, Bianka K.
last_name: Kohegyi
- first_name: Jan Niklas
full_name: Dohrke, Jan Niklas
last_name: Dohrke
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Danyang
full_name: Zhang, Danyang
last_name: Zhang
- first_name: Hinze
full_name: Ho, Hinze
last_name: Ho
- first_name: Saher A.
full_name: Shaikh, Saher A.
last_name: Shaikh
- first_name: Remigijus
full_name: Lape, Remigijus
last_name: Lape
- first_name: James M.
full_name: Krieger, James M.
last_name: Krieger
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
citation:
ama: Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation
of the GluA1/2-γ8 AMPA receptor. Nature Communications. 2022;13. doi:10.1038/s41467-022-28404-7
apa: Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H.,
… Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8
AMPA receptor. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-28404-7
chicago: Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson,
Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and
Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA
Receptor.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-28404-7.
ieee: B. Herguedas et al., “Mechanisms underlying TARP modulation of the
GluA1/2-γ8 AMPA receptor,” Nature Communications, vol. 13. Springer Nature,
2022.
ista: Herguedas B, Kohegyi BK, Dohrke JN, Watson J, Zhang D, Ho H, Shaikh SA, Lape
R, Krieger JM, Greger IH. 2022. Mechanisms underlying TARP modulation of the GluA1/2-γ8
AMPA receptor. Nature Communications. 13, 734.
mla: Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8
AMPA Receptor.” Nature Communications, vol. 13, 734, Springer Nature, 2022,
doi:10.1038/s41467-022-28404-7.
short: B. Herguedas, B.K. Kohegyi, J.N. Dohrke, J. Watson, D. Zhang, H. Ho, S.A.
Shaikh, R. Lape, J.M. Krieger, I.H. Greger, Nature Communications 13 (2022).
date_created: 2022-02-20T23:01:30Z
date_published: 2022-02-08T00:00:00Z
date_updated: 2026-04-02T12:14:43Z
day: '08'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41467-022-28404-7
external_id:
isi:
- '000757297200008'
pmid:
- '35136046'
file:
- access_level: open_access
checksum: d86ee8eabe8b794730729ffbb1a8832e
content_type: application/pdf
creator: dernst
date_created: 2022-02-21T07:59:32Z
date_updated: 2022-02-21T07:59:32Z
file_id: '10778'
file_name: 2022_NatureCommunications_Herguedas.pdf
file_size: 2625540
relation: main_file
success: 1
file_date_updated: 2022-02-21T07:59:32Z
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intvolume: ' 13'
isi: 1
language:
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month: '02'
oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor
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: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 13
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: 2026-07-08T22:31:23Z
day: '09'
department:
- _id: PeJo
- _id: GaNo
- _id: BeBi
- _id: JoDa
doi: 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: 2026-07-08T22:31:24Z
day: '18'
department:
- _id: SaSi
- _id: GaNo
- _id: PeJo
- _id: JoDa
doi: 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: '9549'
abstract:
- lang: eng
text: 'AMPA receptors (AMPARs) mediate the majority of excitatory transmission in
the brain and enable the synaptic plasticity that underlies learning1. A diverse
array of AMPAR signalling complexes are established by receptor auxiliary subunits,
which associate with the AMPAR in various combinations to modulate trafficking,
gating and synaptic strength2. However, their mechanisms of action are poorly
understood. Here we determine cryo-electron microscopy structures of the heteromeric
GluA1–GluA2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR
complex in the forebrain, in both resting and active states. Two TARP-γ8 and two
CNIH2 subunits insert at distinct sites beneath the ligand-binding domains of
the receptor, with site-specific lipids shaping each interaction and affecting
the gating regulation of the AMPARs. Activation of the receptor leads to asymmetry
between GluA1 and GluA2 along the ion conduction path and an outward expansion
of the channel triggers counter-rotations of both auxiliary subunit pairs, promoting
the active-state conformation. In addition, both TARP-γ8 and CNIH2 pivot towards
the pore exit upon activation, extending their reach for cytoplasmic receptor
elements. CNIH2 achieves this through its uniquely extended M2 helix, which has
transformed this endoplasmic reticulum-export factor into a powerful AMPAR modulator
that is capable of providing hippocampal pyramidal neurons with their integrative
synaptic properties. '
acknowledgement: We thank members of the Greger laboratory, B. Herguedas, J. Krieger
and J.-N. Dohrke for comments on the manuscript; J. Krieger and J.-N. Dohrke for
discussion, J. Krieger for help with the normal mode analysis, B. Köhegyi for help
with cryo-EM imaging, V. Chang and K. Suzuki for helping to generate the CNIH2-1D4-HA
stable cell line, M. Carvalho for assistance at early stages of this project, the
LMB scientific computing and the cryo-EM facility for support, P. Emsley for help
with model building, T. Nakane for helpful comments with RELION 3.1 and R. Warshamanage
for helping with EMDA cryo-EM-map processing. We acknowledge the Diamond Light Source
for access and support of the Cryo-EM facilities at the UK national electron bio10
imaging centre (eBIC), proposal EM17434, funded by the Wellcome Trust, MRC and BBSRC.
This work was supported by grants from the Medical Research Council, as part of
United Kingdom Research and Innovation (also known as UK Research and Innovation)
(MC_U105174197) and BBSRC (BB/N002113/1) to I.H.G.
article_processing_charge: No
article_type: original
author:
- first_name: Danyang
full_name: Zhang, Danyang
last_name: Zhang
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Peter M.
full_name: Matthews, Peter M.
last_name: Matthews
- first_name: Ondrej
full_name: Cais, Ondrej
last_name: Cais
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
citation:
ama: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. Gating and modulation of
a hetero-octameric AMPA glutamate receptor. Nature. 2021;594:454-458. doi:10.1038/s41586-021-03613-0
apa: Zhang, D., Watson, J., Matthews, P. M., Cais, O., & Greger, I. H. (2021).
Gating and modulation of a hetero-octameric AMPA glutamate receptor. Nature.
Springer Nature. https://doi.org/10.1038/s41586-021-03613-0
chicago: Zhang, Danyang, Jake Watson, Peter M. Matthews, Ondrej Cais, and Ingo H.
Greger. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate Receptor.”
Nature. Springer Nature, 2021. https://doi.org/10.1038/s41586-021-03613-0.
ieee: D. Zhang, J. Watson, P. M. Matthews, O. Cais, and I. H. Greger, “Gating and
modulation of a hetero-octameric AMPA glutamate receptor,” Nature, vol.
594. Springer Nature, pp. 454–458, 2021.
ista: Zhang D, Watson J, Matthews PM, Cais O, Greger IH. 2021. Gating and modulation
of a hetero-octameric AMPA glutamate receptor. Nature. 594, 454–458.
mla: Zhang, Danyang, et al. “Gating and Modulation of a Hetero-Octameric AMPA Glutamate
Receptor.” Nature, vol. 594, Springer Nature, 2021, pp. 454–58, doi:10.1038/s41586-021-03613-0.
short: D. Zhang, J. Watson, P.M. Matthews, O. Cais, I.H. Greger, Nature 594 (2021)
454–458.
date_created: 2021-06-13T22:01:33Z
date_published: 2021-06-02T00:00:00Z
date_updated: 2026-06-18T19:54:04Z
day: '02'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41586-021-03613-0
external_id:
isi:
- '000657238100003'
pmid:
- '34079129'
intvolume: ' 594'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1038/s41586-021-03613-0
month: '06'
oa: 1
oa_version: Published Version
page: 454-458
pmid: 1
publication: Nature
publication_identifier:
eissn:
- 1476-4687
issn:
- 0028-0836
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Gating and modulation of a hetero-octameric AMPA glutamate receptor
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 594
year: '2021'
...
---
_id: '9985'
abstract:
- lang: eng
text: AMPA receptor (AMPAR) abundance and positioning at excitatory synapses regulates
the strength of transmission. Changes in AMPAR localisation can enact synaptic
plasticity, allowing long-term information storage, and is therefore tightly controlled.
Multiple mechanisms regulating AMPAR synaptic anchoring have been described, but
with limited coherence or comparison between reports, our understanding of this
process is unclear. Here, combining synaptic recordings from mouse hippocampal
slices and super-resolution imaging in dissociated cultures, we compare the contributions
of three AMPAR interaction domains controlling transmission at hippocampal CA1
synapses. We show that the AMPAR C-termini play only a modulatory role, whereas
the extracellular N-terminal domain (NTD) and PDZ interactions of the auxiliary
subunit TARP γ8 are both crucial, and each is sufficient to maintain transmission.
Our data support a model in which γ8 accumulates AMPARs at the postsynaptic density,
where the NTD further tunes their positioning. This interplay between cytosolic
(TARP γ8) and synaptic cleft (NTD) interactions provides versatility to regulate
synaptic transmission and plasticity.
acknowledgement: The authors are very grateful to Andrew Penn for advice and discussions
on surface receptor labelling in slice tissue, dissociated culture transfection,
and for providing tdTomato and BirAER expression plasmids. This work would not have
been possible without support from the Biological Services teams at both the Laboratory
of Molecular Biology and Ares facilities. We are also very grateful to Nick Barry
and Jerome Boulanger of the LMB Light Microscopy facility for support with confocal
and STORM imaging and analysis, Junichi Takagi for providing scFv-Clasp expression
constructs, Veronica Chang for assistance with scFv-Clasp protein production, and
Nejc Kejzar for assistance with cluster analysis. We would like to thank Teru Nakagawa
and Ole Paulsen for critical reading of the manuscript and constructive feedback.
This work was supported by grants from the Medical Research Council (MC_U105174197)
and BBSRC (BB/N002113/1).
article_number: '5083'
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: Alexandra
full_name: Pinggera, Alexandra
last_name: Pinggera
- first_name: Hinze
full_name: Ho, Hinze
last_name: Ho
- first_name: Ingo H.
full_name: Greger, Ingo H.
last_name: Greger
citation:
ama: Watson J, Pinggera A, Ho H, Greger IH. AMPA receptor anchoring at CA1 synapses
is determined by N-terminal domain and TARP γ8 interactions. Nature Communications.
2021;12(1). doi:10.1038/s41467-021-25281-4
apa: Watson, J., Pinggera, A., Ho, H., & Greger, I. H. (2021). AMPA receptor
anchoring at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions.
Nature Communications. Nature Publishing Group. https://doi.org/10.1038/s41467-021-25281-4
chicago: Watson, Jake, Alexandra Pinggera, Hinze Ho, and Ingo H. Greger. “AMPA Receptor
Anchoring at CA1 Synapses Is Determined by N-Terminal Domain and TARP Γ8 Interactions.”
Nature Communications. Nature Publishing Group, 2021. https://doi.org/10.1038/s41467-021-25281-4.
ieee: J. Watson, A. Pinggera, H. Ho, and I. H. Greger, “AMPA receptor anchoring
at CA1 synapses is determined by N-terminal domain and TARP γ8 interactions,”
Nature Communications, vol. 12, no. 1. Nature Publishing Group, 2021.
ista: Watson J, Pinggera A, Ho H, Greger IH. 2021. AMPA receptor anchoring at CA1
synapses is determined by N-terminal domain and TARP γ8 interactions. Nature Communications.
12(1), 5083.
mla: Watson, Jake, et al. “AMPA Receptor Anchoring at CA1 Synapses Is Determined
by N-Terminal Domain and TARP Γ8 Interactions.” Nature Communications,
vol. 12, no. 1, 5083, Nature Publishing Group, 2021, doi:10.1038/s41467-021-25281-4.
short: J. Watson, A. Pinggera, H. Ho, I.H. Greger, Nature Communications 12 (2021).
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