Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement

Ream Al-Hasani, Raajaram Gowrishankar, Gavin P. Schmitz, Christian E. Pedersen, David J. Marcus, Sofia E. Shirley, Taylor E. Hobbs, Abigail J. Elerding, Sophie J. Renaud, Miao Jing, Yulong Li, Veronica A. Alvarez, Julia C. Lemos, Michael R. Bruchas

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The long-range GABAergic input from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is relatively understudied, and therefore its role in reward processing has remained unknown. In the present study, we show, in both male and female mice, that long-range GABAergic projections from the VTA to the ventral NAc shell, but not to the dorsal NAc shell or NAc core, are engaged in reward and reinforcement behavior. We show that this GABAergic projection exclusively synapses on to cholinergic interneurons (CINs) in the ventral NAc shell, thereby serving a specialized function in modulating reinforced reward behavior through the inhibition of ventral NAc shell CINs. These findings highlight the diversity in the structural and functional topography of VTA GABAergic projections, and their neuromodulatory interactions across the dorsoventral gradient of the NAc shell. They also further our understanding of neuronal circuits that are directly implicated in neuropsychiatric conditions such as depression and addiction.

Original languageEnglish (US)
Pages (from-to)1414-1428
Number of pages15
JournalNature neuroscience
Volume24
Issue number10
DOIs
StatePublished - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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