Cited by 45Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesNeuroscience and Neuropharmacology Research

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

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Zhou, Wen-Liang, Kim, Kristen, Ali, Farhan, Pittenger, Steven T., Calarco, Cali A., Mineur, Yann S., Ramakrishnan, Charu, Deisseroth, Karl +2 more·2022·Science Advances

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.

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Authors
Zhou, W.-L., Kim, K., Ali, F., Pittenger, S. T., Calarco, C. A., Mineur, Y. S., Ramakrishnan, C., Deisseroth, K., Kwan, A. C., & Picciotto, M. R.
Affiliations
  • Yale University (US)
  • Stanford University (US)
Corresponding author
Picciotto, Marina R.
Venue
Science Advances
Published
2022-10-21
Volume
8
Issue
42
Pages
eabm5217-eabm5217
ISSN
2375-2548 (ISSN-L)
OpenAlex
W4306855769
Cited by
45
References
64
Citations by year
2026: 5 · 2025: 15 · 2024: 15 · 2023: 10
FWCI
4.42
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (P40OD010996)
  • National Institute on Drug Abuse (R01DA014241, DP1DA050986, P50DA036151, U54DA036151, R37DA014241)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
ventral tegmental area, ventral pallidum, GABAergic neurons, reward value, motivation, reward seeking, dopamine signaling, prediction error, chemogenetic stimulation, optogenetic stimulation

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