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Mol Psychiatry. 2018 Apr 25. doi: 10.1038/s41380-018-0051-3. [Epub ahead of print]

Striatopallidal neurons control avoidance behavior in exploratory tasks.

Author information

1
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
2
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA.
3
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, CONICET, Buenos Aires, C1428ADN, Argentina.
4
FCEN, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina.
5
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.
6
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. lex.kravitz@nih.gov.
7
National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, 20892, USA. lex.kravitz@nih.gov.

Abstract

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.

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