---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '14843'
abstract:
- lang: eng
  text: The coupling between Ca2+ channels and release sensors is a key factor defining
    the signaling properties of a synapse. However, the coupling nanotopography at
    many synapses remains unknown, and it is unclear how it changes during development.
    To address these questions, we examined coupling at the cerebellar inhibitory
    basket cell (BC)-Purkinje cell (PC) synapse. Biophysical analysis of transmission
    by paired recording and intracellular pipette perfusion revealed that the effects
    of exogenous Ca2+ chelators decreased during development, despite constant reliance
    of release on P/Q-type Ca2+ channels. Structural analysis by freeze-fracture replica
    labeling (FRL) and transmission electron microscopy (EM) indicated that presynaptic
    P/Q-type Ca2+ channels formed nanoclusters throughout development, whereas docked
    vesicles were only clustered at later developmental stages. Modeling suggested
    a developmental transformation from a more random to a more clustered coupling
    nanotopography. Thus, presynaptic signaling developmentally approaches a point-to-point
    configuration, optimizing speed, reliability, and energy efficiency of synaptic
    transmission.
acknowledged_ssus:
- _id: EM-Fac
- _id: PreCl
- _id: M-Shop
acknowledgement: We thank Drs. David DiGregorio and Erwin Neher for critically reading
  an earlier version of the manuscript, Ralf Schneggenburger for helpful discussions,
  Benjamin Suter and Katharina Lichter for support with image analysis, Chris Wojtan
  for advice on numerical solution of partial differential equations, Maria Reva for
  help with Ripley analysis, Alois Schlögl for programming, and Akari Hagiwara and
  Toshihisa Ohtsuka for anti-ELKS antibody. We are grateful to Florian Marr, Christina
  Altmutter, and Vanessa Zheden for excellent technical assistance and to Eleftheria
  Kralli-Beller for manuscript editing. This research was supported by the Scientific
  Services Units (SSUs) of ISTA (Electron Microscopy Facility, Preclinical Facility,
  and Machine Shop). The project received funding from the European Research Council
  (ERC) under the European Union’s Horizon 2020 research and innovation program (grant
  agreement no. 692692), the Fonds zur Förderung der Wissenschaftlichen Forschung
  (Z 312-B27, Wittgenstein award; P 36232-B), all to P.J., and a DOC fellowship of
  the Austrian Academy of Sciences to J.-J.C.
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: JingJing
  full_name: Chen, JingJing
  id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
- first_name: Walter
  full_name: Kaufmann, Walter
  id: 3F99E422-F248-11E8-B48F-1D18A9856A87
  last_name: Kaufmann
  orcid: 0000-0001-9735-5315
- first_name: Chong
  full_name: Chen, Chong
  id: 3DFD581A-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
- first_name: Itaru
  full_name: Arai, Itaru
  id: 32A73F6C-F248-11E8-B48F-1D18A9856A87
  last_name: Arai
- first_name: Olena
  full_name: Kim, Olena
  id: 3F8ABDDA-F248-11E8-B48F-1D18A9856A87
  last_name: Kim
  orcid: 0000-0003-2344-1039
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
citation:
  ama: Chen J, Kaufmann W, Chen C, et al. Developmental transformation of Ca2+ channel-vesicle
    nanotopography at a central GABAergic synapse. <i>Neuron</i>. 2024;112(5):755-771.e9.
    doi:<a href="https://doi.org/10.1016/j.neuron.2023.12.002">10.1016/j.neuron.2023.12.002</a>
  apa: Chen, J., Kaufmann, W., Chen, C., Arai,  itaru, Kim, O., Shigemoto, R., &#38;
    Jonas, P. M. (2024). Developmental transformation of Ca2+ channel-vesicle nanotopography
    at a central GABAergic synapse. <i>Neuron</i>. Elsevier. <a href="https://doi.org/10.1016/j.neuron.2023.12.002">https://doi.org/10.1016/j.neuron.2023.12.002</a>
  chicago: Chen, JingJing, Walter Kaufmann, Chong Chen, itaru Arai, Olena Kim, Ryuichi
    Shigemoto, and Peter M Jonas. “Developmental Transformation of Ca2+ Channel-Vesicle
    Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>. Elsevier, 2024.
    <a href="https://doi.org/10.1016/j.neuron.2023.12.002">https://doi.org/10.1016/j.neuron.2023.12.002</a>.
  ieee: J. Chen <i>et al.</i>, “Developmental transformation of Ca2+ channel-vesicle
    nanotopography at a central GABAergic synapse,” <i>Neuron</i>, vol. 112, no. 5.
    Elsevier, p. 755–771.e9, 2024.
  ista: Chen J, Kaufmann W, Chen C, Arai  itaru, Kim O, Shigemoto R, Jonas PM. 2024.
    Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
    GABAergic synapse. Neuron. 112(5), 755–771.e9.
  mla: Chen, JingJing, et al. “Developmental Transformation of Ca2+ Channel-Vesicle
    Nanotopography at a Central GABAergic Synapse.” <i>Neuron</i>, vol. 112, no. 5,
    Elsevier, 2024, p. 755–771.e9, doi:<a href="https://doi.org/10.1016/j.neuron.2023.12.002">10.1016/j.neuron.2023.12.002</a>.
  short: J. Chen, W. Kaufmann, C. Chen,  itaru Arai, O. Kim, R. Shigemoto, P.M. Jonas,
    Neuron 112 (2024) 755–771.e9.
corr_author: '1'
date_created: 2024-01-21T23:00:56Z
date_published: 2024-03-06T00:00:00Z
date_updated: 2026-09-21T22:30:33Z
day: '06'
ddc:
- '570'
department:
- _id: PeJo
- _id: EM-Fac
- _id: RySh
doi: 10.1016/j.neuron.2023.12.002
ec_funded: 1
external_id:
  isi:
  - '001202925700001'
  pmid:
  - '38215739'
file:
- access_level: open_access
  checksum: 30098b4f0209556ddfb3540a23d07ca5
  content_type: application/pdf
  creator: dernst
  date_created: 2025-04-23T14:02:08Z
  date_updated: 2025-04-23T14:02:08Z
  file_id: '19614'
  file_name: 2024_Neuron_Chen.pdf
  file_size: 8192355
  relation: main_file
  success: 1
file_date_updated: 2025-04-23T14:02:08Z
fulldoi: https://doi.org/10.1016/j.neuron.2023.12.002
has_accepted_license: '1'
intvolume: '       112'
isi: 1
issue: '5'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 755-771.e9
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
  grant_number: P36232
  name: Mechanisms of GABA release in hippocampal circuits
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
  grant_number: '25383'
  name: Development of nanodomain coupling between Ca2+ channels and release sensors
    at a central inhibitory synapse
publication: Neuron
publication_identifier:
  eissn:
  - 1097-4199
  issn:
  - 0896-6273
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA Website
    relation: press_release
    url: https://ista.ac.at/en/news/synapses-brought-to-the-point/
  record:
  - id: '15101'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: Developmental transformation of Ca2+ channel-vesicle nanotopography at a central
  GABAergic synapse
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2024'
...
---
OA_place: publisher
_id: '15101'
abstract:
- lang: eng
  text: "The coupling between presynaptic Ca2+ channels and release sensors is a key
    factor that\r\ndetermines speed and efficacy of synapse transmission. At some
    excitatory synapses,\r\nchannel–sensor coupling becomes tighter during development,
    and tightening is often\r\nassociated with a switch in the reliance on different
    Ca2+ channel subtypes. However, the\r\ncoupling topography at many synapses remains
    unknown, and it is unclear how it changes\r\nduring development. To address this
    question, we analyzed the coupling configuration at the\r\ncerebellar basket cell
    (BC) to Purkinje cell (PC) synapse at different developmental stages,\r\ncombining
    biophysical analysis, structural analysis, and modeling.\r\nQuantal analysis of
    BC–PC indicated that release probability decreased, while the\r\nnumber of functional
    sites increased during development. Although transmitter release\r\npersistently
    relied on P/Q-type Ca2+ channels in the time period postnatal day 7–23, effects\r\nof
    the Ca2+ chelator EGTA and BAPTA applied by intracellular pipette perfusion decreased\r\nduring
    development, indicative of tightening of source-sensor coupling. Furthermore,\r\npresynaptic
    action potentials became shorter during development, suggesting reduced\r\nefficacy
    of Ca2+ channel activation.\r\nStructural analysis by freeze-fracture replica
    labeling (FRL) and transmission electron\r\nmicroscopy (EM) indicated that presynaptic
    P/Q-type Ca2+ channels formed nanoclusters\r\nthroughout development, whereas
    docked vesicles were only clustered at later\r\ndevelopmental stages. The number
    of functional release sites correlated better with the AZ\r\nnumber early in development,
    but match better with the Ca2+ channel cluster number at later\r\nstages.\r\nModeling
    suggested a developmental transformation from a more random to a more\r\nclustered
    coupling nanotopography. Thus, presynaptic signaling developmentally approaches\r\na
    point-to-point configuration, optimizing speed, reliability, and energy efficiency
    of synaptic\r\ntransmission."
acknowledged_ssus:
- _id: EM-Fac
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: JingJing
  full_name: Chen, JingJing
  id: 2C4E65C8-F248-11E8-B48F-1D18A9856A87
  last_name: Chen
citation:
  ama: Chen J. Developmental transformation of nanodomain coupling between Ca2+ channels
    and release sensors at a central GABAergic synapse. 2024. doi:<a href="https://doi.org/10.15479/at:ista:15101">10.15479/at:ista:15101</a>
  apa: Chen, J. (2024). <i>Developmental transformation of nanodomain coupling between
    Ca2+ channels and release sensors at a central GABAergic synapse</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:15101">https://doi.org/10.15479/at:ista:15101</a>
  chicago: Chen, JingJing. “Developmental Transformation of Nanodomain Coupling between
    Ca2+ Channels and Release Sensors at a Central GABAergic Synapse.” Institute of
    Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:15101">https://doi.org/10.15479/at:ista:15101</a>.
  ieee: J. Chen, “Developmental transformation of nanodomain coupling between Ca2+
    channels and release sensors at a central GABAergic synapse,” Institute of Science
    and Technology Austria, 2024.
  ista: Chen J. 2024. Developmental transformation of nanodomain coupling between
    Ca2+ channels and release sensors at a central GABAergic synapse. Institute of
    Science and Technology Austria.
  mla: Chen, JingJing. <i>Developmental Transformation of Nanodomain Coupling between
    Ca2+ Channels and Release Sensors at a Central GABAergic Synapse</i>. Institute
    of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:15101">10.15479/at:ista:15101</a>.
  short: J. Chen, Developmental Transformation of Nanodomain Coupling between Ca2+
    Channels and Release Sensors at a Central GABAergic Synapse, Institute of Science
    and Technology Austria, 2024.
corr_author: '1'
date_created: 2024-03-11T10:09:54Z
date_published: 2024-03-11T00:00:00Z
date_updated: 2026-04-07T13:24:22Z
day: '11'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: PeJo
doi: 10.15479/at:ista:15101
ec_funded: 1
file:
- access_level: closed
  checksum: db4947474ffa271e66c254b6fe876a55
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: jchen
  date_created: 2024-03-11T14:10:58Z
  date_updated: 2024-04-02T22:30:03Z
  embargo_to: open_access
  file_id: '15104'
  file_name: Thesis_Jingjing CHEN.docx
  file_size: 11271363
  relation: source_file
- access_level: open_access
  checksum: a5eeae8b5702cd540f5d03469bc33dde
  content_type: application/pdf
  creator: jchen
  date_created: 2024-03-11T14:11:06Z
  date_updated: 2024-04-02T22:30:03Z
  embargo: 2024-04-01
  file_id: '15105'
  file_name: Thesis_Jingjing CHEN_merged.pdf
  file_size: 16627311
  relation: main_file
file_date_updated: 2024-04-02T22:30:03Z
fulldoi: https://doi.org/10.15479/at:ista:15101
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '84'
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: 25C5A090-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Z00312
  name: Synaptic communication in neuronal microcircuits
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
  grant_number: P36232
  name: Mechanisms of GABA release in hippocampal circuits
- _id: 26B66A3E-B435-11E9-9278-68D0E5697425
  grant_number: '25383'
  name: Development of nanodomain coupling between Ca2+ channels and release sensors
    at a central inhibitory synapse
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '14843'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
title: Developmental transformation of nanodomain coupling between Ca2+ channels and
  release sensors at a central GABAergic synapse
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...