Investigating GABAergic Projections of the Ventral Pallidum’s Hedonic Hotspot Using a Dual-Virus Approach

Abstract

The ventral pallidum (VP) is a brain region implicated in reward-related behaviors, motivation, and addiction. The posterior half of the VP is coined as the “hedonic hotspot”, a subregion that amplifies liking reactions in response to palatable stimuli. The feature does not remain true for the anterior half of the VP, indicating a divergence in functionality. The extent of the VP’s heterogeneity with respect to circuit-level connections is yet to be explored fully. This project aimed to distinguish the difference in downstream projection targets between the anterior and posterior VP that give rise to the hedonic hotspot. A fluorescent tracer virus was injected into either the anterior or posterior VP in rats to specifically target GABAergic neurons. Post-mortem brain tissue processing and imaging was performed for visualization of projections. Quantification data showed that the posterior VP projects more robustly to the lateral habenula and lateral hypothalamus than the anterior VP. This finding suggests that certain hedonic hotspot neurons may wire together to these 2 regions. This synaptic connection could be a potential target for pharmacological modulation in cases of substance use disorders. Further elucidation of VP inputs and outputs will allow us to better understand the mechanisms that underlie reward pursuit, addiction and relapse.