Identification of GABAergic neurons innervating the zebrafish lateral habenula

Habenula neurons are constantly active. The level of activity affects mood and behaviour, with increased activity in the lateral habenula reflecting exposure to punishment and a switch to passive coping and depression. Here, we identify GABAergic neurons that could reduce activity in the lateral hab...

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Main Authors: Ramaswamy, Mahathi, Cheng, Ruey-Kuang, Jesuthasan, Suresh
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Journal Article
Language:English
Published: 2022
Subjects:
Online Access:https://hdl.handle.net/10356/161243
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author Ramaswamy, Mahathi
Cheng, Ruey-Kuang
Jesuthasan, Suresh
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Ramaswamy, Mahathi
Cheng, Ruey-Kuang
Jesuthasan, Suresh
author_sort Ramaswamy, Mahathi
collection NTU
description Habenula neurons are constantly active. The level of activity affects mood and behaviour, with increased activity in the lateral habenula reflecting exposure to punishment and a switch to passive coping and depression. Here, we identify GABAergic neurons that could reduce activity in the lateral habenula of larval zebrafish. GAD65/67 immunohistochemistry and imaging of gad1b:DsRed transgenic fish suggest the presence of GABAergic terminals in the neuropil and between cell bodies in the lateral habenula. Retrograde tracing with the lipophilic dye DiD suggests that the former derives from the thalamus, while the latter originates from a group of cells in the posterior hypothalamus that are located between the posterior tuberal nucleus and hypothalamic lobes. Two-photon calcium imaging indicates that blue light causes excitation of thalamic GABAergic neurons and terminals in the neuropil, while a subpopulation of lateral habenula neurons show reduced intracellular calcium levels. Whole-cell electrophysiological recording indicates that blue light reduces membrane potential of lateral habenula neurons. These observations suggest that GABAergic input from the thalamus may mediate inhibition in the zebrafish lateral habenula. Mechanisms governing release of GABA from the neurons in the posterior hypothalamus, which are likely to be in the tuberomammillary nucleus, remain to be defined.
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spelling ntu-10356/1612432023-03-05T16:54:27Z Identification of GABAergic neurons innervating the zebrafish lateral habenula Ramaswamy, Mahathi Cheng, Ruey-Kuang Jesuthasan, Suresh Lee Kong Chian School of Medicine (LKCMedicine) NUS Graduate School for Integrative Sciences and Engineering Institute of Molecular and Cell Biology Science::Medicine Thalamus Neural Tracing Habenula neurons are constantly active. The level of activity affects mood and behaviour, with increased activity in the lateral habenula reflecting exposure to punishment and a switch to passive coping and depression. Here, we identify GABAergic neurons that could reduce activity in the lateral habenula of larval zebrafish. GAD65/67 immunohistochemistry and imaging of gad1b:DsRed transgenic fish suggest the presence of GABAergic terminals in the neuropil and between cell bodies in the lateral habenula. Retrograde tracing with the lipophilic dye DiD suggests that the former derives from the thalamus, while the latter originates from a group of cells in the posterior hypothalamus that are located between the posterior tuberal nucleus and hypothalamic lobes. Two-photon calcium imaging indicates that blue light causes excitation of thalamic GABAergic neurons and terminals in the neuropil, while a subpopulation of lateral habenula neurons show reduced intracellular calcium levels. Whole-cell electrophysiological recording indicates that blue light reduces membrane potential of lateral habenula neurons. These observations suggest that GABAergic input from the thalamus may mediate inhibition in the zebrafish lateral habenula. Mechanisms governing release of GABA from the neurons in the posterior hypothalamus, which are likely to be in the tuberomammillary nucleus, remain to be defined. Ministry of Education (MOE) Nanyang Technological University Published version This research was supported by a Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Start-Up Grant and the Singapore Ministry of Education under its Academic Research Fund Tier 2 (MOE2017-T2-058) and Tier 1 (MOE2016-T1-001-152) awards. 2022-08-22T05:55:05Z 2022-08-22T05:55:05Z 2020 Journal Article Ramaswamy, M., Cheng, R. & Jesuthasan, S. (2020). Identification of GABAergic neurons innervating the zebrafish lateral habenula. European Journal of Neuroscience, 52(8), 3918-3928. https://dx.doi.org/10.1111/ejn.14843 0953-816X https://hdl.handle.net/10356/161243 10.1111/ejn.14843 32464693 2-s2.0-85087292516 8 52 3918 3928 en MOE2017-T2-058 MOE2016-T1-001-152 European Journal of Neuroscience © 2020 The Authors. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. application/pdf
spellingShingle Science::Medicine
Thalamus
Neural Tracing
Ramaswamy, Mahathi
Cheng, Ruey-Kuang
Jesuthasan, Suresh
Identification of GABAergic neurons innervating the zebrafish lateral habenula
title Identification of GABAergic neurons innervating the zebrafish lateral habenula
title_full Identification of GABAergic neurons innervating the zebrafish lateral habenula
title_fullStr Identification of GABAergic neurons innervating the zebrafish lateral habenula
title_full_unstemmed Identification of GABAergic neurons innervating the zebrafish lateral habenula
title_short Identification of GABAergic neurons innervating the zebrafish lateral habenula
title_sort identification of gabaergic neurons innervating the zebrafish lateral habenula
topic Science::Medicine
Thalamus
Neural Tracing
url https://hdl.handle.net/10356/161243
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AT jesuthasansuresh identificationofgabaergicneuronsinnervatingthezebrafishlateralhabenula