PROJECT SUMMARY Stress is known to dysregulate a range of behaviors, impacting normal responses to environmental stimuli, and producing long-lasting internal state changes. Corticotropin-releasing factor (CRF) is a stress-associated neuropeptide and CRF signaling underlies many stress-induced neurobiological changes. Studies have focused on CRF signaling in the PVN and amygdala. However, within the basal ganglia circuitry, the ventral pallidum (VP) contains high expression of CRF receptors (CRF1). Yet, CRF-CRF1 signaling within VP remains unstudied. Stress-induced changes to reward-consumption have been described, but the neurobiological mechanism(s) underlying these alterations are not fully understood. Activity of a GABAergic VP population projecting to the nucleus accumbens (ventral arkypallidal) has been shown to potentiate reward consumption. Our preliminary data suggests that VP CRF1+ cells are part of this ventral arkypallidal population; thus, VP CRF-CRF1 signaling represents one potential mechanism by which stress potentiates reward consumption behaviors. This proposal investigates the neurochemical, connectivity, and functional properties of VP CRF1+ neurons. The central hypothesis of this proposal is that CRF1+ VP neurons are a GABAergic arkypallidal population, and that CRF1 signaling in these cells increases their overall activity following acute CRF application or stress exposure. I will determine the abundance, distribution, neurochemical composition, and connectivity of the VP CRF1 population (Aim1). This foundational investigation is important as the identity and connectivity of VP populations have been shown to impact behavioral output. To probe the electrophysiological properties of this novel population, I will measure intrinsic excitability and excitatory and inhibitory synaptic transmission in VP CRF1+ and CRF1- cells, both basally and following acute application of CRF (Aim2). This will provide the first evidence that VP CRF1+ cells are functionally distinct from CRF1- cells and that VP neurons are directly sensitive to CRF. The mechanism underlying stress-mediated adaptations of VP circuitry is important, as these changes may have negative consequences for individuals. I will investigate the impact of stress on intrinsic excitability and synaptic strength of VP CRF1+ and CRF1- populations, and the dependence of these alterations on CRF1 signaling (Aim3). This will provide evidence that VP is sensitive to stress and undergoes CRF1-mediated functional adaptations following stress exposure. With the guidance of my sponsor, Dr. Julia C Lemos, and co-sponsor, Dr. Kevin Wickman, completion of the proposed study will not only address a crucial scientific question but provide me with extensive technical, conceptual, and professional training. This research will contribute to the long-term goal of elucidating the mechanism underlying motivational deficits following stress and my development as an independent researcher.