Chronic Stress Induces Activity, Synaptic, and Transcriptional Remodeling of the Lateral Habenula Associated with Deficits in Motivated Behaviors.
chronic stress
depression
dorsal raphe nucleus
entopeduncular nucleus
lateral habenula
ventral tegmental area
Journal
Neuron
ISSN: 1097-4199
Titre abrégé: Neuron
Pays: United States
ID NLM: 8809320
Informations de publication
Date de publication:
04 12 2019
04 12 2019
Historique:
received:
02
01
2019
revised:
21
07
2019
accepted:
06
09
2019
pubmed:
2
11
2019
medline:
24
3
2020
entrez:
2
11
2019
Statut:
ppublish
Résumé
Chronic stress (CS) is a major risk factor for the development of depression. Here, we demonstrate that CS-induced hyperactivity in ventral tegmental area (VTA)-projecting lateral habenula (LHb) neurons is associated with increased passive coping (PC), but not anxiety or anhedonia. LHb→VTA neurons in mice with increased PC show increased burst and tonic firing as well as synaptic adaptations in excitatory inputs from the entopeduncular nucleus (EP). In vivo manipulations of EP→LHb or LHb→VTA neurons selectively alter PC and effort-related motivation. Conversely, dorsal raphe (DR)-projecting LHb neurons do not show CS-induced hyperactivity and are targeted indirectly by the EP. Using single-cell transcriptomics, we reveal a set of genes that can collectively serve as biomarkers to identify mice with increased PC and differentiate LHb→VTA from LHb→DR neurons. Together, we provide a set of biological markers at the level of genes, synapses, cells, and circuits that define a distinctive CS-induced behavioral phenotype.
Identifiants
pubmed: 31672263
pii: S0896-6273(19)30778-0
doi: 10.1016/j.neuron.2019.09.005
pmc: PMC6895430
mid: NIHMS1540004
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
899-915.e8Subventions
Organisme : NIMH NIH HHS
ID : R01 MH107742
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH112721
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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