Opponent control of behavioral reinforcement by inhibitory and excitatory projections from the ventral pallidum

Lauren Faget,Navarre Gutierrez-Reed,Adam Mcpherson,Ji Hoon Yoo,Vivien Zell,Davide Dulcis,Reed Ressler,Thomas S Hnasko,Elizabeth Souter

doi:10.1038/s41467-018-03125-y

Abstract

The ventral pallidum (VP) lies at the interface between sensory, motor, and cognitive processing—with a particular role in mounting behavioral responses to rewards. Though the VP is predominantly GABAergic, glutamate neurons were recently identified, though their relative abundances and respective roles are unknown. Here, we show that VP glutamate neurons are concentrated in the rostral ventromedial VP and project to qualitatively similar targets as do VP GABA neurons. At the functional level, we used optogenetics to show that activity in VP GABA neurons can drive positive reinforcement, particularly through projections to the ventral tegmental area (VTA). On the other hand, activation of VP glutamate neurons leads to behavioral avoidance, particularly through projections to the lateral habenula. These findings highlight cell-type and projection-target specific roles for VP neurons in behavioral reinforcement, dysregulation of which could contribute to the emergence of negative symptoms associated with drug addiction and other neuropsychiatric disease.

Highlights

The ventral pallidum (VP) lies at the interface between sensory, motor, and cognitive processing—with a particular role in mounting behavioral responses to rewards
Labeling by dual in situ hybridization was consistent with low rates of VGLUT2/VGAT co-localization in the VP (Supplementary Fig. 1A, B). These findings suggest that VGLUT2+ VP neurons are essentially distinct from cholinergic cells, that a small fraction co-localize for GABA markers, and that PV is expressed in subpopulations of both inhibitory and excitatory VP neurons, consistent with recent studies[33,34]
Multiple studies have shown that VP neurons fire in response to rewards or reward-related stimuli and that VP manipulations can profoundly influence reward-seeking behaviors[2,8]

Summary

Introduction

The ventral pallidum (VP) lies at the interface between sensory, motor, and cognitive processing—with a particular role in mounting behavioral responses to rewards. Another study demonstrated that chemogenetic inhibition of the RVP blunts cue-induced reinstatement, and inhibiting the CVP blocks cocaine-primed reinstatement[29] Another source of heterogeneity that has received less attention is the neurochemical identity of VP cells. While ventral tegmental area (VTA)-projecting VP neurons have been identified as functionally GABAergic[31], VP glutamate projections to VTA were reported[32]. It remains unknown whether VP glutamate neurons functionally cooperate with or oppose VP GABA projections in reward processes. We optogenetically manipulated VP glutamate versus GABA cells, or specific VP projections, to demonstrate that these cell types can play functionally opponent roles in the control of motivated behavior

Methods

Results

Conclusion