---
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. <i>Cell Reports</i>. 2025;44(8). doi:<a href="https://doi.org/10.1016/j.celrep.2025.116080">10.1016/j.celrep.2025.116080</a>
  apa: Watson, J., Vargas Barroso, V. M., &#38; Jonas, P. M. (2025). Cell-specific
    wiring routes information flow through hippocampal CA3. <i>Cell Reports</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.celrep.2025.116080">https://doi.org/10.1016/j.celrep.2025.116080</a>
  chicago: Watson, Jake, Victor M Vargas Barroso, and Peter M Jonas. “Cell-Specific
    Wiring Routes Information Flow through Hippocampal CA3.” <i>Cell Reports</i>.
    Elsevier, 2025. <a href="https://doi.org/10.1016/j.celrep.2025.116080">https://doi.org/10.1016/j.celrep.2025.116080</a>.
  ieee: J. Watson, V. M. Vargas Barroso, and P. M. Jonas, “Cell-specific wiring routes
    information flow through hippocampal CA3,” <i>Cell Reports</i>, 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.” <i>Cell Reports</i>, vol. 44, no. 8, 116080, Elsevier, 2025,
    doi:<a href="https://doi.org/10.1016/j.celrep.2025.116080">10.1016/j.celrep.2025.116080</a>.
  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
_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. <i>Cell</i>. 2025;188(2):501-514.e18.
    doi:<a href="https://doi.org/10.1016/j.cell.2024.11.022">10.1016/j.cell.2024.11.022</a>
  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. <i>Cell</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.cell.2024.11.022">https://doi.org/10.1016/j.cell.2024.11.022</a>
  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.” <i>Cell</i>. Elsevier, 2025. <a href="https://doi.org/10.1016/j.cell.2024.11.022">https://doi.org/10.1016/j.cell.2024.11.022</a>.
  ieee: J. Watson <i>et al.</i>, “Human hippocampal CA3 uses specific functional connectivity
    rules for efficient associative memory,” <i>Cell</i>, 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.” <i>Cell</i>, vol. 188, no. 2, Elsevier,
    2025, p. 501–514.e18, doi:<a href="https://doi.org/10.1016/j.cell.2024.11.022">10.1016/j.cell.2024.11.022</a>.
  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
  file_id: '18884'
  file_name: 2025_Cell_Watson.pdf
  file_size: 14082343
  relation: main_file
  success: 1
file_date_updated: 2025-01-27T08:46:33Z
has_accepted_license: '1'
intvolume: '       188'
isi: 1
issue: '2'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 501-514.e18
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: 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:
  record:
  - id: '18688'
    relation: earlier_version
    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'
...
---
_id: '12515'
abstract:
- lang: eng
  text: "Introduction: The olfactory system in most mammals is divided into several
    subsystems based on the anatomical locations of the neuroreceptor cells involved
    and the receptor families that are expressed. In addition to the main olfactory
    system and the vomeronasal system, a range of olfactory subsystems converge onto
    the transition zone located between the main olfactory bulb (MOB) and the accessory
    olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL
    contains specialized glomeruli that receive noncanonical sensory afferences and
    which interact with the MOB and AOB. Little is known regarding the olfactory subsystems
    of mammals other than laboratory rodents.\r\nMethods: We have focused on characterizing
    the OL in the red fox by performing general and specific histological stainings
    on serial sections, using both single and double immunohistochemical and lectin-histochemical
    labeling techniques.\r\nResults: As a result, we have been able to determine that
    the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development
    and complexity.\r\nDiscussion: This makes this species a novel mammalian model,
    the study of which could improve our understanding of the noncanonical pathways
    involved in the processing of chemosensory cues."
acknowledgement: This work was partially supported by a grant from “Consello Social
  Universidade de Santiago de Compostela” 2022-PU004.We would like to show special
  gratitude to Prof. Ludwig Wagner (Medical University, Vienna) for kindly providing
  us with the secretagogin antibody. We thank the Wildlife Recovery Centres of Galicia,
  Dirección Xeral de Patrimonio Natural (Xunta de Galicia, Spain), and Federación
  Galega de Caza for providing the red foxes used in this study.
article_number: '1097467'
article_processing_charge: No
article_type: original
author:
- first_name: Irene
  full_name: Ortiz-Leal, Irene
  last_name: Ortiz-Leal
- first_name: Mateo V.
  full_name: Torres, Mateo V.
  last_name: Torres
- first_name: Victor M
  full_name: Vargas Barroso, Victor M
  id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
  last_name: Vargas Barroso
- first_name: Luis Eusebio
  full_name: Fidalgo, Luis Eusebio
  last_name: Fidalgo
- first_name: Ana María
  full_name: López-Beceiro, Ana María
  last_name: López-Beceiro
- first_name: Jorge A.
  full_name: Larriva-Sahd, Jorge A.
  last_name: Larriva-Sahd
- first_name: Pablo
  full_name: Sánchez-Quinteiro, Pablo
  last_name: Sánchez-Quinteiro
citation:
  ama: Ortiz-Leal I, Torres MV, Vargas Barroso VM, et al. The olfactory limbus of
    the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb
    pathway. <i>Frontiers in Neuroanatomy</i>. 2023;16. doi:<a href="https://doi.org/10.3389/fnana.2022.1097467">10.3389/fnana.2022.1097467</a>
  apa: Ortiz-Leal, I., Torres, M. V., Vargas Barroso, V. M., Fidalgo, L. E., López-Beceiro,
    A. M., Larriva-Sahd, J. A., &#38; Sánchez-Quinteiro, P. (2023). The olfactory
    limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory
    bulb pathway. <i>Frontiers in Neuroanatomy</i>. Frontiers. <a href="https://doi.org/10.3389/fnana.2022.1097467">https://doi.org/10.3389/fnana.2022.1097467</a>
  chicago: Ortiz-Leal, Irene, Mateo V. Torres, Victor M Vargas Barroso, Luis Eusebio
    Fidalgo, Ana María López-Beceiro, Jorge A. Larriva-Sahd, and Pablo Sánchez-Quinteiro.
    “The Olfactory Limbus of the Red Fox (Vulpes Vulpes). New Insights Regarding a
    Noncanonical Olfactory Bulb Pathway.” <i>Frontiers in Neuroanatomy</i>. Frontiers,
    2023. <a href="https://doi.org/10.3389/fnana.2022.1097467">https://doi.org/10.3389/fnana.2022.1097467</a>.
  ieee: I. Ortiz-Leal <i>et al.</i>, “The olfactory limbus of the red fox (Vulpes
    vulpes). New insights regarding a noncanonical olfactory bulb pathway,” <i>Frontiers
    in Neuroanatomy</i>, vol. 16. Frontiers, 2023.
  ista: Ortiz-Leal I, Torres MV, Vargas Barroso VM, Fidalgo LE, López-Beceiro AM,
    Larriva-Sahd JA, Sánchez-Quinteiro P. 2023. The olfactory limbus of the red fox
    (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway.
    Frontiers in Neuroanatomy. 16, 1097467.
  mla: Ortiz-Leal, Irene, et al. “The Olfactory Limbus of the Red Fox (Vulpes Vulpes).
    New Insights Regarding a Noncanonical Olfactory Bulb Pathway.” <i>Frontiers in
    Neuroanatomy</i>, vol. 16, 1097467, Frontiers, 2023, doi:<a href="https://doi.org/10.3389/fnana.2022.1097467">10.3389/fnana.2022.1097467</a>.
  short: I. Ortiz-Leal, M.V. Torres, V.M. Vargas Barroso, L.E. Fidalgo, A.M. López-Beceiro,
    J.A. Larriva-Sahd, P. Sánchez-Quinteiro, Frontiers in Neuroanatomy 16 (2023).
date_created: 2023-02-05T23:01:00Z
date_published: 2023-01-10T00:00:00Z
date_updated: 2023-08-16T11:37:52Z
day: '10'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.3389/fnana.2022.1097467
external_id:
  isi:
  - '000919786900001'
  pmid:
  - '36704406'
file:
- access_level: open_access
  checksum: 49cd40f3bda6f267079427042e7d15e3
  content_type: application/pdf
  creator: dernst
  date_created: 2023-02-06T07:56:14Z
  date_updated: 2023-02-06T07:56:14Z
  file_id: '12518'
  file_name: 2022_FrontiersNeuroanatomy_OrtizLeal.pdf
  file_size: 21943473
  relation: main_file
  success: 1
file_date_updated: 2023-02-06T07:56:14Z
has_accepted_license: '1'
intvolume: '        16'
isi: 1
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
pmid: 1
publication: Frontiers in Neuroanatomy
publication_identifier:
  eissn:
  - 1662-5129
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding
  a noncanonical olfactory bulb pathway
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: 16
year: '2023'
...
---
_id: '9438'
abstract:
- lang: eng
  text: Rigorous investigation of synaptic transmission requires analysis of unitary
    synaptic events by simultaneous recording from presynaptic terminals and postsynaptic
    target neurons. However, this has been achieved at only a limited number of model
    synapses, including the squid giant synapse and the mammalian calyx of Held. Cortical
    presynaptic terminals have been largely inaccessible to direct presynaptic recording,
    due to their small size. Here, we describe a protocol for improved subcellular
    patch-clamp recording in rat and mouse brain slices, with the synapse in a largely
    intact environment. Slice preparation takes ~2 h, recording ~3 h and post hoc
    morphological analysis 2 d. Single presynaptic hippocampal mossy fiber terminals
    are stimulated minimally invasively in the bouton-attached configuration, in which
    the cytoplasmic content remains unperturbed, or in the whole-bouton configuration,
    in which the cytoplasmic composition can be precisely controlled. Paired pre–postsynaptic
    recordings can be integrated with biocytin labeling and morphological analysis,
    allowing correlative investigation of synapse structure and function. Paired recordings
    can be obtained from mossy fiber terminals in slices from both rats and mice,
    implying applicability to genetically modified synapses. Paired recordings can
    also be performed together with axon tract stimulation or optogenetic activation,
    allowing comparison of unitary and compound synaptic events in the same target
    cell. Finally, paired recordings can be combined with spontaneous event analysis,
    permitting collection of miniature events generated at a single identified synapse.
    In conclusion, the subcellular patch-clamp techniques detailed here should facilitate
    analysis of biophysics, plasticity and circuit function of cortical synapses in
    the mammalian central nervous system.
acknowledged_ssus:
- _id: M-Shop
acknowledgement: This project received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation programme
  (grant agreement no. 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen
  Forschung (Z 312-B27, Wittgenstein award to P.J., V 739-B27 to C.B.M.). We are grateful
  to F. Marr and C. Altmutter for excellent technical assistance and cell reconstruction,
  E. Kralli-Beller for manuscript editing, and the Scientific Service Units of IST
  Austria, especially T. Asenov and Miba machine shop, for maximally efficient support.
article_processing_charge: No
article_type: original
author:
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Yuji
  full_name: Okamoto, Yuji
  id: 3337E116-F248-11E8-B48F-1D18A9856A87
  last_name: Okamoto
  orcid: 0000-0003-0408-6094
- first_name: Carolina
  full_name: Borges Merjane, Carolina
  id: 4305C450-F248-11E8-B48F-1D18A9856A87
  last_name: Borges Merjane
  orcid: 0000-0003-0005-401X
- first_name: Victor M
  full_name: Vargas Barroso, Victor M
  id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
  last_name: Vargas Barroso
- first_name: Benjamin
  full_name: Suter, Benjamin
  id: 4952F31E-F248-11E8-B48F-1D18A9856A87
  last_name: Suter
  orcid: 0000-0002-9885-6936
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
    PM. Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
    pre- and postsynaptic recording at cortical synapses. <i>Nature Protocols</i>.
    2021;16(6):2947–2967. doi:<a href="https://doi.org/10.1038/s41596-021-00526-0">10.1038/s41596-021-00526-0</a>
  apa: Vandael, D. H., Okamoto, Y., Borges Merjane, C., Vargas Barroso, V. M., Suter,
    B., &#38; Jonas, P. M. (2021). Subcellular patch-clamp techniques for single-bouton
    stimulation and simultaneous pre- and postsynaptic recording at cortical synapses.
    <i>Nature Protocols</i>. Springer Nature. <a href="https://doi.org/10.1038/s41596-021-00526-0">https://doi.org/10.1038/s41596-021-00526-0</a>
  chicago: Vandael, David H, Yuji Okamoto, Carolina Borges Merjane, Victor M Vargas
    Barroso, Benjamin Suter, and Peter M Jonas. “Subcellular Patch-Clamp Techniques
    for Single-Bouton Stimulation and Simultaneous Pre- and Postsynaptic Recording
    at Cortical Synapses.” <i>Nature Protocols</i>. Springer Nature, 2021. <a href="https://doi.org/10.1038/s41596-021-00526-0">https://doi.org/10.1038/s41596-021-00526-0</a>.
  ieee: D. H. Vandael, Y. Okamoto, C. Borges Merjane, V. M. Vargas Barroso, B. Suter,
    and P. M. Jonas, “Subcellular patch-clamp techniques for single-bouton stimulation
    and simultaneous pre- and postsynaptic recording at cortical synapses,” <i>Nature
    Protocols</i>, vol. 16, no. 6. Springer Nature, pp. 2947–2967, 2021.
  ista: Vandael DH, Okamoto Y, Borges Merjane C, Vargas Barroso VM, Suter B, Jonas
    PM. 2021. Subcellular patch-clamp techniques for single-bouton stimulation and
    simultaneous pre- and postsynaptic recording at cortical synapses. Nature Protocols.
    16(6), 2947–2967.
  mla: Vandael, David H., et al. “Subcellular Patch-Clamp Techniques for Single-Bouton
    Stimulation and Simultaneous Pre- and Postsynaptic Recording at Cortical Synapses.”
    <i>Nature Protocols</i>, vol. 16, no. 6, Springer Nature, 2021, pp. 2947–2967,
    doi:<a href="https://doi.org/10.1038/s41596-021-00526-0">10.1038/s41596-021-00526-0</a>.
  short: D.H. Vandael, Y. Okamoto, C. Borges Merjane, V.M. Vargas Barroso, B. Suter,
    P.M. Jonas, Nature Protocols 16 (2021) 2947–2967.
corr_author: '1'
date_created: 2021-05-30T22:01:24Z
date_published: 2021-06-01T00:00:00Z
date_updated: 2025-04-22T22:30:43Z
day: '01'
ddc:
- '570'
department:
- _id: PeJo
doi: 10.1038/s41596-021-00526-0
ec_funded: 1
external_id:
  isi:
  - '000650528700003'
  pmid:
  - '33990799'
file:
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intvolume: '        16'
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language:
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oa_version: Submitted Version
page: 2947–2967
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: 2696E7FE-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: V00739
  name: Structural plasticity at mossy fiber-CA3 synapses
publication: Nature Protocols
publication_identifier:
  eissn:
  - 1750-2799
  issn:
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publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Subcellular patch-clamp techniques for single-bouton stimulation and simultaneous
  pre- and postsynaptic recording at cortical synapses
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 16
year: '2021'
...