---
_id: '13173'
abstract:
- lang: eng
  text: GABAB receptor (GBR) activation inhibits neurotransmitter release in axon
    terminals in the brain, except in medial habenula (MHb) terminals, which show
    robust potentiation. However, mechanisms underlying this enigmatic potentiation
    remain elusive. Here, we report that GBR activation on MHb terminals induces an
    activity-dependent transition from a facilitating, tonic to a depressing, phasic
    neurotransmitter release mode. This transition is accompanied by a 4.1-fold increase
    in readily releasable vesicle pool (RRP) size and a 3.5-fold increase of docked
    synaptic vesicles at the presynaptic active zone (AZ). Strikingly, tonic and phasic
    release exhibit distinct coupling distances and are selectively affected by deletion
    of synaptoporin (SPO) and Ca2+-dependent activator protein for secretion 2 (CAPS2),
    respectively. SPO modulates augmentation, the short-term plasticity associated
    with tonic release, and CAPS2 retains the increased RRP for initial responses
    in phasic response trains. Double pre-embedding immunolabeling confirmed the co-localization
    of CAPS2 and SPO inside the same terminal. The cytosolic protein CAPS2 showed
    a synaptic vesicle (SV)-associated distribution similar to the vesicular transmembrane
    protein SPO. A newly developed “Flash and Freeze-fracture” method revealed the
    release of SPO-associated vesicles in both tonic and phasic modes and activity-dependent
    recruitment of CAPS2 to the AZ during phasic release, which lasted several minutes.
    Overall, these results indicate that GBR activation translocates CAPS2 to the
    AZ along with the fusion of CAPS2-associated SVs, contributing to a persistent
    RRP increase. Thus, we discovered structural and molecular mechanisms underlying
    tonic and phasic neurotransmitter release and their transition by GBR activation
    in MHb terminals.
article_processing_charge: No
author:
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  ama: Shigemoto R. Transition from tonic to phasic neurotransmitter release by presynaptic
    GABAB receptor activation in medial habenula terminals. 2023. doi:<a href="https://doi.org/10.15479/AT:ISTA:13173">10.15479/AT:ISTA:13173</a>
  apa: Shigemoto, R. (2023). Transition from tonic to phasic neurotransmitter release
    by presynaptic GABAB receptor activation in medial habenula terminals. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:13173">https://doi.org/10.15479/AT:ISTA:13173</a>
  chicago: Shigemoto, Ryuichi. “Transition from Tonic to Phasic Neurotransmitter Release
    by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals.” Institute
    of Science and Technology Austria, 2023. <a href="https://doi.org/10.15479/AT:ISTA:13173">https://doi.org/10.15479/AT:ISTA:13173</a>.
  ieee: R. Shigemoto, “Transition from tonic to phasic neurotransmitter release by
    presynaptic GABAB receptor activation in medial habenula terminals.” Institute
    of Science and Technology Austria, 2023.
  ista: Shigemoto R. 2023. Transition from tonic to phasic neurotransmitter release
    by presynaptic GABAB receptor activation in medial habenula terminals, Institute
    of Science and Technology Austria, <a href="https://doi.org/10.15479/AT:ISTA:13173">10.15479/AT:ISTA:13173</a>.
  mla: Shigemoto, Ryuichi. <i>Transition from Tonic to Phasic Neurotransmitter Release
    by Presynaptic GABAB Receptor Activation in Medial Habenula Terminals</i>. Institute
    of Science and Technology Austria, 2023, doi:<a href="https://doi.org/10.15479/AT:ISTA:13173">10.15479/AT:ISTA:13173</a>.
  short: R. Shigemoto, (2023).
date_created: 2023-06-29T13:16:42Z
date_published: 2023-07-29T00:00:00Z
date_updated: 2024-02-21T12:19:26Z
day: '29'
ddc:
- '571'
department:
- _id: RySh
doi: 10.15479/AT:ISTA:13173
file:
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  creator: shigemot
  date_created: 2023-06-29T13:11:22Z
  date_updated: 2023-11-17T14:30:44Z
  description: After review an updated version of the data is provided
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- access_level: open_access
  checksum: c07860eb82b4d367245f1b589fe5c250
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file_date_updated: 2024-02-06T07:21:43Z
has_accepted_license: '1'
keyword:
- medial habenula
- GABAB receptor
- vesicle release
- Flash and Freeze
- Flash and Freeze-fracture
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '07'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
status: public
title: Transition from tonic to phasic neurotransmitter release by presynaptic GABAB
  receptor activation in medial habenula terminals
tmp:
  image: /images/cc_by_nc.png
  legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
  short: CC BY-NC (4.0)
type: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...