Ventral pallidum GABA and glutamate neurons drive approach and avoidance through distinct modulation of VTA cell types

Lauren Faget (), Lucie Oriol, Wen-Chun Lee, Vivien Zell, Cody Sargent, Andrew Flores, Nick G. Hollon, Dhakshin Ramanathan and Thomas S. Hnasko ()
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Lauren Faget: University of California San Diego
Lucie Oriol: University of California San Diego
Wen-Chun Lee: University of California San Diego
Vivien Zell: University of California San Diego
Cody Sargent: University of California San Diego
Andrew Flores: University of California San Diego
Nick G. Hollon: San Diego
Dhakshin Ramanathan: Veterans Affairs San Diego Healthcare System
Thomas S. Hnasko: University of California San Diego

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract The ventral pallidum (VP) contains GABA and glutamate neurons projecting to ventral tegmental area (VTA) whose stimulation drives approach and avoidance, respectively. Yet little is known about the mechanisms by which VP cell types shape VTA activity and drive behavior. Here, we found that both VP GABA and glutamate neurons were activated during approach to reward or by delivery of an aversive stimulus. Stimulation of VP GABA neurons inhibited VTA GABA, but activated dopamine and glutamate neurons. Remarkably, stimulation-evoked activation was behavior-contingent such that VTA recruitment was inhibited when evoked by the subject’s own action. Conversely, VP glutamate neurons activated VTA GABA, as well as dopamine and glutamate neurons, despite driving aversion. However, VP glutamate neurons evoked dopamine in aversion-associated ventromedial nucleus accumbens (NAc), but reduced dopamine release in reward-associated dorsomedial NAc. These findings show how heterogeneous VP projections to VTA can be engaged to shape approach and avoidance behaviors.

Date: 2024
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DOI: 10.1038/s41467-024-48340-y

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