Ventral Pallidal GABAergic Neuron Calcium Activity Encodes Cue-Driven Reward Seeking and Persists in the Absence of Reward Delivery

Abstract

Reward-seeking behavior is often initiated by environmental cues that signal reward availability. This is a necessary behavioral response; however, cue reactivity and reward-seeking behavior can become maladaptive. To better understand how cue-elicited reward seeking becomes maladaptive, it is important to understand the neural circuits involved in assigning appetitive value to rewarding cues and actions. Ventral pallidum (VP) neurons are known to contribute to cue-elicited reward-seeking behavior and have heterogeneous responses in a discriminative stimulus (DS) task. The VP neuronal subtypes and output pathways that encode distinct aspects of the DS task remain unknown. Here, we used an intersectional viral approach with fiber photometry to record bulk calcium activity in VP GABAergic (VP GABA) neurons in male and female rats as they learned and performed the DS task. We found that VP GABA neurons are excited by reward-predictive cues but not neutral cues and that this response develops over time. We also found that this cue-evoked response predicts reward-seeking behavior and that inhibiting this VP GABA activity during cue presentation decreases reward-seeking behavior. Additionally, we found increased VP GABA calcium activity at the time of expected reward delivery, which occurred even on trials when reward was omitted. Together, these findings suggest that VP GABA neurons encode reward expectation, and calcium activity in these neurons encodes the vigor of cue-elicited reward seeking.SIGNIFICANCE STATEMENTVP circuitry is a major driver of cue-evoked behaviors. Previous work has found that VP neurons have heterogenous responses and contributions to reward-seeking behavior. This functional heterogeneity is because of differences of neurochemical subtypes and projections of VP neurons. Understanding the heterogenous responses among and within VP neuronal cell types is a necessary step in further understanding how cue-evoked behavior becomes maladaptive. Our work explores the canonical GABAergic VP neuron and how the calcium activity of these cells encodes components of cue-evoked reward seeking, including the vigor and persistence of reward seeking.