VTA GABA Neurons at the Interface of Stress and Reward

Abstract

The ventral tegmental area (VTA) is best known for its robust dopaminergic projections to forebrain regions and their critical role in regulating reward, motivation, cognition, and aversion. However, the VTA is not only made of dopamine (DA) cells, as approximately 30% of cells in the VTA are GABA neurons. These neurons play a dual role, as VTA GABA neurons provide both local inhibition of VTA DA neurons and long-range inhibition of several distal brain regions. VTA GABA neurons have increasingly been recognized as potent mediators of reward and aversion in their own right, as well as potential targets for the treatment of addiction, depression, and other stress-linked disorders. In this review article, we dissect the circuit architecture, physiology, and behavioral roles of VTA GABA neurons and suggest critical gaps to be addressed.

Keywords: GABA; circuits; reward; stress; ventral tegmental area (VTA).

Figure 1

Major afferents and efferents of VTA GABA neurons. (A) Major projection targets of VTA GABA neurons within and beyond the VTA. (B) Major inputs onto VTA GABA neurons. Abbreviations: BNST, bed nucleus of the stria terminalis; CeA, central amygdala; DRN, dorsal raphe nucleus; LHb, lateral habenula; LH, lateral hypothalamus; NAc, nucleus accumbens; PAG, periaqueductal gray; PFC, prefrontal cortex; SC, superior colliculus; VP, ventral pallidum; VTA, ventral tegmental area.