Ventral pallidal modulation of aversion processing

Brain Res. 2019 Jun 15;1713:62-69. doi: 10.1016/j.brainres.2018.10.010. Epub 2018 Oct 6.

Abstract

Responding to aversive and rewarding stimuli is essential to survival. The ventral pallidum (VP) is a critical node in the mesolimbic network, being the primary output of the nucleus accumbens and projecting to the lateral habenula (LHb) and ventral tegmental area (VTA). The VP is thus poised to modulate the habenula-tegmental circuitry and contribute to processing both rewarding and aversive stimuli. Here, we integrate human functional imaging, behavioral pharmacology in rodents, and recent optogenetic circuit dissection studies of the VP with a focus on the role of the neurochemically-distinct subpopulations in aversion processing. These recent results support a model in which glutamatergic VP neurons play a unique role in aversion processing, while canonical GABAergic VP neurons promote reinforcement and encode the hedonic value of reward. Genetic ablation of glutamatergic, but not GABAergic VP neurons abolishes devaluation of natural reward (sucrose) by pairing with an aversive stimulus (lithium chloride injection). Both of these populations modulate activity throughout the LHb and VTA, which is necessary for expression of adaptive behavior in response to rewarding or aversive stimuli. Future work will address how neuromodulators such as endogenous opioids or dopamine shape function and plasticity within these distinct populations of VP neurons, when these subpopulations are engaged during learning responses to rewarding and aversive stimuli, and how their activity is altered in models of reward-related disorders. Answering these questions will be necessary to understand the basis and ultimately develop targeted therapies for disorders of reward/aversion processing, such as affective, chronic pain and substance use disorders.

Keywords: Dopamine; Electrophysiology; GABA; Glutamate; Habenula; Ventral tegmental area.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Affect
  • Animals
  • Avoidance Learning / physiology*
  • Basal Forebrain / metabolism*
  • Basal Forebrain / pathology
  • Dopamine / metabolism*
  • Dopamine / physiology
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology
  • GABAergic Neurons / metabolism
  • Glutamic Acid / metabolism
  • Habenula / metabolism
  • Humans
  • Neural Pathways / physiology
  • Nucleus Accumbens / metabolism
  • Reward
  • Ventral Tegmental Area / metabolism

Substances

  • Glutamic Acid
  • Dopamine