Gabaergic pallidal-hypothalamic regulation of approach/avoidance conflict behaviors

The National Institute of Mental Health awarded $158,696 to the University of Puerto Rico Medical Sciences Campus on December 2, 2026, under the Mental Health Research Grants program (CFDA 93.242) to investigate how GABAergic neurons in the ventral pallidum and their projections to the lateral hypothalamus encode and modulate opposing behavioral responses during motivational conflict.

The research uses fiber photometry and optogenetics to characterize how ventral pallidum GABAergic neuronal activity encodes reward- and threat-related cues during the platform-mediated avoidance task, a behavioral paradigm in which mice learn to approach a sucrose reward signaled by light and avoid mild footshock signaled by tone. The study employs closed-loop silencing of ventral pallidum GABAergic neurons during key behavioral epochs to determine whether temporally precise intervention impairs approach or avoidance responses, with the goal of clarifying how these motivational circuits contribute to adaptive decision-making processes often disrupted in anxiety, depression, and addiction-related disorders.

The award is a Project Grant with a period of performance extending from December 2, 2026, through June 4, 2029. Performance takes place in Puerto Rico, with the University of Puerto Rico Medical Sciences Campus serving as the recipient organization under its parent institution, the University of Puerto Rico.

Abstract

The ventral pallidum (VP) and lateral hypothalamus (LH) are key nodes in motivational circuits regulating both approach and avoidance behaviors. VP gabaergic (vpgaba) neurons, which comprise most of the VP, are implicated in encoding both reward and threat-related signals, positioning them as potential integrators of motivational conflict. The vpgaba-LH pathway has been primarily linked to reward-seeking behavior, raising the possibility that this projection may selectively promote approach under conditions of conflict. However, its functional role when animals simultaneously evaluate competing drives remains unclear. Investigating both the broader vpgaba population and this projection will help clarify how these circuits contribute to adaptive decision- making processes often disrupted in anxiety, depression, and addiction-related disorders. This F32 proposal will investigate how vpgaba neurons and the vpgaba-LH pathway encode and modulate opposing behavioral responses during motivational conflict. I will use the platform-mediated avoidance (PMA) task, a behavioral paradigm developed by my sponsor. In this task, mice learn to approach a sucrose reward signaled by a light CUE and to avoid a mild footshock signaled by a tone by stepping onto a safety platform far from the reward port. During conflict trials, both cues are presented simultaneously, requiring mice to dynamically weigh the competing drives of reward-seeking and threat avoidance in real time. In aim 1, i will use fiber photometry and optogenetics to characterize how vpgaba neuronal activity encodes reward- and threat-related cues, as well as approach and avoidance behaviors during the PMA task. I will also determine whether temporally precise, closed-loop silencing of vpgaba neurons during key behavioral epochs can impair approach or avoidance responses. In aim 2, i will combine projection-specific fiber photometry and optogenetics to examine how vpgaba-LH neurons contribute to conflict resolution. I will record vpgaba-LH activity during PMA to determine whether this pathway selectively encodes approach over avoidance. Using whole-CUE and closed-loop optogenetic activation and silencing, i will test whether this projection is necessary and/or sufficient to bias behavior toward approach in the face of conflict. Together, these studies will clarify how vpgaba circuits guide adaptive decision-making and establish a mechanistic framework for understanding maladaptive behaviors in neuropsychiatric disease. These studies will directly support my transition to research independence and help establish the foundation for my lab focused on the neural circuits of motivation and decision-making.