Exploration of Projection Targets of Caudal GABAergic Ventral Pallidum Neurons for Basis of Functional Heterogeneity

Abstract

The ventral pallidum is a brain region known to play a major role in mesocorticolimbic circuits underlying learning, motivation, and reward-evoked behavior. It is known that the ventral pallidum is a structure heterogeneous in nature, but the extent of its heterogeneity in projection targets is yet to be explored thoroughly. Experiments targeting the ventral pallidum speculate the existence of hotspots, defined sites known to modulate specific behavioral responses to stimuli, within this area of the basal ganglia. The caudal ventral pallidum was found to be a hedonic hotspot, enhancing liking reactions to sucrose following both opioid and orexin injections. This project aims to explore the extent of heterogeneity within the caudal ventral pallidum on the basis of projection regions. As the ventral pallidum signals primarily with GABA, a dual viral mixture was unilaterally injected in rat models to target VP GABAergic neurons and identify their downstream projections. Fluorescent microscopy and image processing were then used to quantify these projection signals in the lateral habenula, lateral hypothalamus, and subthalamic nucleus. Degree of viral expression in the aforementioned projections was compared among rats receiving either a caudal- or central-VP injection. Greater knowledge of this subregional heterogeneity could help develop targeted medications and uncover specialized treatments in the cases of addiction and relapse, highlighting the need for understanding the circuit differences between the ventral pallidal subregions.