Striatopallidal neurons control avoidance behavior in exploratory tasks.


Journal

Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835

Informations de publication

Date de publication:
02 2020
Historique:
received: 25 07 2017
accepted: 19 02 2018
revised: 05 02 2018
pubmed: 27 4 2018
medline: 15 12 2020
entrez: 27 4 2018
Statut: ppublish

Résumé

The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict paradigms in mice: the elevated zero maze and open field. Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other neural populations, increased avoidance of the open areas in both tasks, in a manner that was dissociable from global changes in movement. Population calcium activity of dorsomedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs contributes to heightened avoidance behavior. Consistently, artificial disruption of iMSN output with optogenetic stimulation heightened avoidance of open areas of these tasks, while inhibition of iMSN output reduced avoidance. We conclude that dorsomedial striatal iMSNs control approach-avoidance conflicts in exploratory tasks, and highlight this neural population as a potential target for reducing avoidance in anxiety disorders.

Identifiants

pubmed: 29695836
doi: 10.1038/s41380-018-0051-3
pii: 10.1038/s41380-018-0051-3
pmc: PMC6202282
mid: NIHMS944711
doi:

Substances chimiques

Receptors, Dopamine D2 0

Types de publication

Journal Article Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

491-505

Subventions

Organisme : Intramural NIH HHS
ID : Z99 DK999999
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DK075096-01
Pays : United States

Commentaires et corrections

Type : ErratumIn

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Auteurs

Kimberly H LeBlanc (KH)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Tanisha D London (TD)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Ilona Szczot (I)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Miriam E Bocarsly (ME)

National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA.

Danielle M Friend (DM)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Katrina P Nguyen (KP)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Marda M Mengesha (MM)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Marcelo Rubinstein (M)

Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET, Buenos Aires, C1428ADN, Argentina.
FCEN, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina.
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Veronica A Alvarez (VA)

National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA.

Alexxai V Kravitz (AV)

National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. lex.kravitz@nih.gov.
National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, 20892, USA. lex.kravitz@nih.gov.

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