Activity of a direct VTA to ventral pallidum GABA pathway encodes unconditioned reward value and sustains motivation for reward

Author:

Zhou Wen-Liang1ORCID,Kim Kristen2ORCID,Ali Farhan1ORCID,Pittenger Steven T.1,Calarco Cali A.2ORCID,Mineur Yann S.1ORCID,Ramakrishnan Charu3ORCID,Deisseroth Karl3ORCID,Kwan Alex C.1ORCID,Picciotto Marina R.14ORCID

Affiliation:

1. Department of Psychiatry, Yale University, 34 Park Street, New Haven, CT 06508, USA.

2. Interdepartmental Neuroscience Program, Yale School of Medicine, New Haven, CT 06520, USA.

3. Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

4. Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT 06520, USA.

Abstract

Dopamine signaling from the ventral tegmental area (VTA) plays critical roles in reward-related behaviors, but less is known about the functions of neighboring VTA GABAergic neurons. We show here that a primary target of VTA GABA projection neurons is the ventral pallidum (VP). Activity of VTA-to-VP–projecting GABA neurons correlates consistently with size and palatability of the reward and does not change following cue learning, providing a direct measure of reward value. Chemogenetic stimulation of this GABA projection increased activity of a subset of VP neurons that were active while mice were seeking reward. Optogenetic stimulation of this pathway improved performance in a cue-reward task and maintained motivation to work for reward over days. This VTA GABA projection provides information about reward value directly to the VP, likely distinct from the prediction error signal carried by VTA dopamine neurons.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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