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Synaptic potentiation onto habenula neurons in learned helplessness model of depression

The cellular basis of depressive disorders is poorly understood1. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected po...

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Autores principales: Li, Bo, Piriz, Joaquin, Mirrione, Martine, Chung, ChiHye, Proulx, Christophe D., Schulz, Daniela, Henn, Fritz, Malinow, Roberto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285101/
https://www.ncbi.nlm.nih.gov/pubmed/21350486
http://dx.doi.org/10.1038/nature09742
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author Li, Bo
Piriz, Joaquin
Mirrione, Martine
Chung, ChiHye
Proulx, Christophe D.
Schulz, Daniela
Henn, Fritz
Malinow, Roberto
author_facet Li, Bo
Piriz, Joaquin
Mirrione, Martine
Chung, ChiHye
Proulx, Christophe D.
Schulz, Daniela
Henn, Fritz
Malinow, Roberto
author_sort Li, Bo
collection PubMed
description The cellular basis of depressive disorders is poorly understood1. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (i.e. disappointment or anticipation of a negative outcome)2, 3, 4. LHb neurons project to and modulate dopamine-rich regions such as the ventral-tegmental area (VTA)2, 5 that control reward-seeking behavior6 and participate in depressive disorders7. Here we show in two learned helplessness models of depression that excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal’s helplessness behavior and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective on depressed patients8, 9, dramatically suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behavior in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression.
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spelling pubmed-32851012012-02-23 Synaptic potentiation onto habenula neurons in learned helplessness model of depression Li, Bo Piriz, Joaquin Mirrione, Martine Chung, ChiHye Proulx, Christophe D. Schulz, Daniela Henn, Fritz Malinow, Roberto Nature Article The cellular basis of depressive disorders is poorly understood1. Recent studies in monkeys indicate that neurons in the lateral habenula (LHb), a nucleus that mediates communication between forebrain and midbrain structures, can increase their activity when an animal fails to receive an expected positive reward or receives a stimulus that predicts aversive conditions (i.e. disappointment or anticipation of a negative outcome)2, 3, 4. LHb neurons project to and modulate dopamine-rich regions such as the ventral-tegmental area (VTA)2, 5 that control reward-seeking behavior6 and participate in depressive disorders7. Here we show in two learned helplessness models of depression that excitatory synapses onto LHb neurons projecting to the VTA are potentiated. Synaptic potentiation correlates with an animal’s helplessness behavior and is due to an enhanced presynaptic release probability. Depleting transmitter release by repeated electrical stimulation of LHb afferents, using a protocol that can be effective on depressed patients8, 9, dramatically suppresses synaptic drive onto VTA-projecting LHb neurons in brain slices and can significantly reduce learned helplessness behavior in rats. Our results indicate that increased presynaptic action onto LHb neurons contributes to the rodent learned helplessness model of depression. 2011-02-24 /pmc/articles/PMC3285101/ /pubmed/21350486 http://dx.doi.org/10.1038/nature09742 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Li, Bo
Piriz, Joaquin
Mirrione, Martine
Chung, ChiHye
Proulx, Christophe D.
Schulz, Daniela
Henn, Fritz
Malinow, Roberto
Synaptic potentiation onto habenula neurons in learned helplessness model of depression
title Synaptic potentiation onto habenula neurons in learned helplessness model of depression
title_full Synaptic potentiation onto habenula neurons in learned helplessness model of depression
title_fullStr Synaptic potentiation onto habenula neurons in learned helplessness model of depression
title_full_unstemmed Synaptic potentiation onto habenula neurons in learned helplessness model of depression
title_short Synaptic potentiation onto habenula neurons in learned helplessness model of depression
title_sort synaptic potentiation onto habenula neurons in learned helplessness model of depression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3285101/
https://www.ncbi.nlm.nih.gov/pubmed/21350486
http://dx.doi.org/10.1038/nature09742
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