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A hypothalamus-habenula circuit controls aversion
Encoding and predicting aversive events are critical functions of circuits that support survival and emotional well-being. Maladaptive circuit changes in emotional valence processing can underlie the pathophysiology of affective disorders. The lateral habenula (LHb) has been linked to aversion and m...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756229/ https://www.ncbi.nlm.nih.gov/pubmed/30755721 http://dx.doi.org/10.1038/s41380-019-0369-5 |
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author | Lazaridis, Iakovos Tzortzi, Ourania Weglage, Moritz Märtin, Antje Xuan, Yang Parent, Marc Johansson, Yvonne Fuzik, Janos Fürth, Daniel Fenno, Lief E. Ramakrishnan, Charu Silberberg, Gilad Deisseroth, Karl Carlén, Marie Meletis, Konstantinos |
author_facet | Lazaridis, Iakovos Tzortzi, Ourania Weglage, Moritz Märtin, Antje Xuan, Yang Parent, Marc Johansson, Yvonne Fuzik, Janos Fürth, Daniel Fenno, Lief E. Ramakrishnan, Charu Silberberg, Gilad Deisseroth, Karl Carlén, Marie Meletis, Konstantinos |
author_sort | Lazaridis, Iakovos |
collection | PubMed |
description | Encoding and predicting aversive events are critical functions of circuits that support survival and emotional well-being. Maladaptive circuit changes in emotional valence processing can underlie the pathophysiology of affective disorders. The lateral habenula (LHb) has been linked to aversion and mood regulation through modulation of the dopamine and serotonin systems. We have defined the identity and function of glutamatergic (Vglut2) control of the LHb, comparing the role of inputs originating in the globus pallidus internal segment (GPi), and lateral hypothalamic area (LHA), respectively. We found that LHb-projecting LHA neurons, and not the proposed GABA/glutamate co-releasing GPi neurons, are responsible for encoding negative value. Monosynaptic rabies tracing of the presynaptic organization revealed a predominantly limbic input onto LHA Vglut2 neurons, while sensorimotor inputs were more prominent onto GABA/glutamate co-releasing GPi neurons. We further recorded the activity of LHA Vglut2 neurons, by imaging calcium dynamics in response to appetitive versus aversive events in conditioning paradigms. LHA Vglut2 neurons formed activity clusters representing distinct reward or aversion signals, including a population that responded to mild foot shocks and predicted aversive events. We found that the LHb-projecting LHA Vglut2 neurons encode negative valence and rapidly develop a prediction signal for negative events. These findings establish the glutamatergic LHA-LHb circuit as a critical node in value processing. |
format | Online Article Text |
id | pubmed-6756229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67562292019-09-26 A hypothalamus-habenula circuit controls aversion Lazaridis, Iakovos Tzortzi, Ourania Weglage, Moritz Märtin, Antje Xuan, Yang Parent, Marc Johansson, Yvonne Fuzik, Janos Fürth, Daniel Fenno, Lief E. Ramakrishnan, Charu Silberberg, Gilad Deisseroth, Karl Carlén, Marie Meletis, Konstantinos Mol Psychiatry Article Encoding and predicting aversive events are critical functions of circuits that support survival and emotional well-being. Maladaptive circuit changes in emotional valence processing can underlie the pathophysiology of affective disorders. The lateral habenula (LHb) has been linked to aversion and mood regulation through modulation of the dopamine and serotonin systems. We have defined the identity and function of glutamatergic (Vglut2) control of the LHb, comparing the role of inputs originating in the globus pallidus internal segment (GPi), and lateral hypothalamic area (LHA), respectively. We found that LHb-projecting LHA neurons, and not the proposed GABA/glutamate co-releasing GPi neurons, are responsible for encoding negative value. Monosynaptic rabies tracing of the presynaptic organization revealed a predominantly limbic input onto LHA Vglut2 neurons, while sensorimotor inputs were more prominent onto GABA/glutamate co-releasing GPi neurons. We further recorded the activity of LHA Vglut2 neurons, by imaging calcium dynamics in response to appetitive versus aversive events in conditioning paradigms. LHA Vglut2 neurons formed activity clusters representing distinct reward or aversion signals, including a population that responded to mild foot shocks and predicted aversive events. We found that the LHb-projecting LHA Vglut2 neurons encode negative valence and rapidly develop a prediction signal for negative events. These findings establish the glutamatergic LHA-LHb circuit as a critical node in value processing. Nature Publishing Group UK 2019-02-12 2019 /pmc/articles/PMC6756229/ /pubmed/30755721 http://dx.doi.org/10.1038/s41380-019-0369-5 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Lazaridis, Iakovos Tzortzi, Ourania Weglage, Moritz Märtin, Antje Xuan, Yang Parent, Marc Johansson, Yvonne Fuzik, Janos Fürth, Daniel Fenno, Lief E. Ramakrishnan, Charu Silberberg, Gilad Deisseroth, Karl Carlén, Marie Meletis, Konstantinos A hypothalamus-habenula circuit controls aversion |
title | A hypothalamus-habenula circuit controls aversion |
title_full | A hypothalamus-habenula circuit controls aversion |
title_fullStr | A hypothalamus-habenula circuit controls aversion |
title_full_unstemmed | A hypothalamus-habenula circuit controls aversion |
title_short | A hypothalamus-habenula circuit controls aversion |
title_sort | hypothalamus-habenula circuit controls aversion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756229/ https://www.ncbi.nlm.nih.gov/pubmed/30755721 http://dx.doi.org/10.1038/s41380-019-0369-5 |
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