GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish
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...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2024.1461148/full |
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| author | Nisa Roy Satoshi Ogawa Sachiko Tsuda Ishwar S. Parhar |
| author_facet | Nisa Roy Satoshi Ogawa Sachiko Tsuda Ishwar S. Parhar |
| author_sort | Nisa Roy |
| collection | DOAJ |
| description | 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 a GPR139 antagonist or agonist. Furthermore, KCl-evoked calcium transients were reduced by the GPR139 antagonist and co-treatment of the GPR139 antagonist–agonist. 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, solitarily, it functions in governing the fear consolidation process via activation of the ventral habenula neurons in zebrafish. |
| format | Article |
| id | doaj-art-f3ecc10bd4f04b4ea63ddeb5b12bfcde |
| institution | OA Journals |
| issn | 1662-453X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj-art-f3ecc10bd4f04b4ea63ddeb5b12bfcde2025-08-20T02:34:02ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2024-12-011810.3389/fnins.2024.14611481461148GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafishNisa Roy0Satoshi Ogawa1Sachiko Tsuda2Ishwar S. Parhar3Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Subang Jaya, MalaysiaJeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Subang Jaya, MalaysiaGraduate School of Science and Engineering, Saitama University, Saitama, JapanJeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, Subang Jaya, MalaysiaG 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 a GPR139 antagonist or agonist. Furthermore, KCl-evoked calcium transients were reduced by the GPR139 antagonist and co-treatment of the GPR139 antagonist–agonist. 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, solitarily, it functions in governing the fear consolidation process via activation of the ventral habenula neurons in zebrafish.https://www.frontiersin.org/articles/10.3389/fnins.2024.1461148/fullGPR139habenulafear memorycalcium imagingconditioned place avoidance |
| spellingShingle | Nisa Roy Satoshi Ogawa Sachiko Tsuda Ishwar S. Parhar GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish Frontiers in Neuroscience GPR139 habenula fear memory calcium imaging conditioned place avoidance |
| title | GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish |
| title_full | GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish |
| title_fullStr | GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish |
| title_full_unstemmed | GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish |
| title_short | GPR139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish |
| title_sort | gpr139 agonist and antagonist differentially regulate retrieval and consolidation of fear memory in the zebrafish |
| topic | GPR139 habenula fear memory calcium imaging conditioned place avoidance |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2024.1461148/full |
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