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ORIGINAL RESEARCH article

Front. Neurosci.
Sec. Decision Neuroscience
Volume 18 - 2024 | doi: 10.3389/fnins.2024.1461148

GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish

Provisionally accepted
Nisa Roy Nisa Roy 1Satoshi Ogawa Satoshi Ogawa 2Sachiko Tsuda Sachiko Tsuda 3Ishwar S Parhar Ishwar S Parhar 4*
  • 1 National Institutes of Health (NIH), Bethesda, United States
  • 2 Monash University Malaysia, Subang Jaya, Selangor, Malaysia
  • 3 Saitama University, Saitama, Saitama, Japan
  • 4 University of Toyama, Toyama, Toyama, Japan

The final, formatted version of the article will be published soon.

    G protein-coupled receptor 139 (GPR139), a highly conserved orphan receptor, is predominantly expressed in the habenula of vertebrate species. Habenula is an ancient epithalamic structure, which is critical to comprehending adaptive behaviors in vertebrates. We have previously demonstrated the role of GPR139 agonists in fear-associated decision-making processes in zebrafish. However, how GPR139 signaling in the habenula modulates such adaptive behavioral responses remains unsolved. Fish centrally administered with a synthetic antagonist for human GPR139 (NCRW0005-F05) exhibited significant suppression of odorant cue (alarm substance, AS)-induced fear learning in the conditioned place avoidance paradigm.On the other hand, co-treatment with a GPR139 antagonist and a synthetic agonist for human GPR139 (JNJ-63533054) interrupted the fear conditioning process by significantly reducing locomotion during post-conditioning. Calcium imaging of acute brain slices showed a significant increase in peak amplitude of calcium transients in the habenula upon bath application of either GPR139 antagonist or agonist. Furthermore, KCl-evoked calcium transients were reduced by the GPR139 antagonist and co-treatment of the GPR139 antagonistagonist. These results suggest that the GPR139 antagonist did not block the inhibitory action of the GPR139 agonist in the decision-making process during the fear-retrieval phase; however,

    Keywords: GPR139, Habenula, fear memory, calcium imaging, conditioned place avoidance

    Received: 07 Jul 2024; Accepted: 15 Nov 2024.

    Copyright: © 2024 Roy, Ogawa, Tsuda and Parhar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ishwar S Parhar, University of Toyama, Toyama, 930-0194, Toyama, Japan

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