---
OA_place: publisher
_id: '19271'
abstract:
- lang: eng
  text: "The medial habenula (MHb) is implicated in regulating emotional responses\r\nto
    aversive events. Studies in zebrafish have identified a remarkable morphological\r\nleft-right
    asymmetry in the dorsal habenula (zebrafish equivalent of mammalian\r\nMHb)-to-interpeduncular
    nucleus (IPN) pathway and its left-side specific role in\r\nmodulating fear responses.
    However, there is little evidence for structural or\r\nfunctional lateralization
    in the mammalian MHb-IPN pathway.\r\nHere, I investigated the synaptic properties
    of the left and right MHb\r\nafferents to the IPN in mice and addressed whether
    these synaptic connections\r\nselectively influence the expression of conditioned
    fear in mice. My findings reveal\r\nthat each individual IPN neuron receives inputs
    from both left and right MHb.\r\nElectrophysiological recordings from the same
    postsynaptic IPN neurons\r\ndemonstrate that the left MHb-originating synapses
    exhibit lower release\r\nprobability and higher \U0001D6FE-aminobutyric acid type
    B receptor (GABABR)-mediated\r\npotentiation compared to the right MHb-originating
    synapses. Interestingly,\r\nchemogenetic inhibition of cholinergic neurons in
    the left but not the right MHb\r\nsignificantly attenuated cue-dependent fear
    recall. Furthermore, conditional\r\ndeletion of GABABR in the left MHb interfered
    with the recall of cued fear memory,\r\nwhereas that in the right MHb neurons
    spared fear memory expression.\r\nCollectively, I demonstrate a functional asymmetry
    of the MHb in mice,\r\nrevealing a predominant role for GABABR-mediated signaling
    in the left MHb-IPN\r\npathway in the modulation of fear memories. These findings
    suggest that\r\nlateralized pathways could represent a fundamental principle in
    the neural\r\nregulation of emotion across species."
acknowledged_ssus:
- _id: PreCl
- _id: M-Shop
acknowledgement: "I would like to thank the European Research Council and European
  Commission, under the European Union’s Horizon 2020 research and innovation program
  (ERC grant agreement no. 694539 to Ryuichi Shigemoto and the Marie Skłodowska-Curie
  grant agreement no. 665385 to Cihan Önal), and the Austrian Neuroscience Association
  for providing financial support and opportunities, which were important in allowing
  me to present my work. I also wish to thank the\r\nPreclinical Facility, especially
  Michael Schunn, for always welcoming me from my earliest days as an intern. My gratitude
  goes as well to the Miba Machine Shop, in particular Todor Asenov, Astrit Arslani,
  and Thomas Menner, whose technical expertise often saved the day."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Hüseyin C
  full_name: Önal, Hüseyin C
  id: 4659D740-F248-11E8-B48F-1D18A9856A87
  last_name: Önal
  orcid: 0000-0002-2771-2011
citation:
  ama: Önal C. Asymmetrical modulation of fear expression via GABAB receptors in the
    mouse medial habenula. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-19271">10.15479/AT-ISTA-19271</a>
  apa: Önal, C. (2025). <i>Asymmetrical modulation of fear expression via GABAB receptors
    in the mouse medial habenula</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT-ISTA-19271">https://doi.org/10.15479/AT-ISTA-19271</a>
  chicago: Önal, Cihan. “Asymmetrical Modulation of Fear Expression via GABAB Receptors
    in the Mouse Medial Habenula.” Institute of Science and Technology Austria, 2025.
    <a href="https://doi.org/10.15479/AT-ISTA-19271">https://doi.org/10.15479/AT-ISTA-19271</a>.
  ieee: C. Önal, “Asymmetrical modulation of fear expression via GABAB receptors in
    the mouse medial habenula,” Institute of Science and Technology Austria, 2025.
  ista: Önal C. 2025. Asymmetrical modulation of fear expression via GABAB receptors
    in the mouse medial habenula. Institute of Science and Technology Austria.
  mla: Önal, Cihan. <i>Asymmetrical Modulation of Fear Expression via GABAB Receptors
    in the Mouse Medial Habenula</i>. Institute of Science and Technology Austria,
    2025, doi:<a href="https://doi.org/10.15479/AT-ISTA-19271">10.15479/AT-ISTA-19271</a>.
  short: C. Önal, Asymmetrical Modulation of Fear Expression via GABAB Receptors in
    the Mouse Medial Habenula, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-02-28T14:15:53Z
date_published: 2025-03-04T00:00:00Z
date_updated: 2026-04-07T12:40:42Z
day: '04'
ddc:
- '570'
- '571'
- '573'
- '599'
degree_awarded: PhD
department:
- _id: GradSch
- _id: RySh
doi: 10.15479/AT-ISTA-19271
ec_funded: 1
file:
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  date_created: 2025-02-28T13:57:01Z
  date_updated: 2026-02-01T23:30:02Z
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  date_updated: 2026-02-01T23:30:02Z
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has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '03'
oa: 1
oa_version: Published Version
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication_identifier:
  eissn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '9437'
    relation: part_of_dissertation
    status: public
  - id: '15084'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
title: Asymmetrical modulation of fear expression via GABAB receptors in the mouse
  medial habenula
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: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...