PROJECTION-SPECIFIC CONTROL OF AFFECTIVE AND SOCIAL BEHAVIOR BY VENTRAL PALLIDUM DLX-EXPRESSING GABAERGIC NEURONS IN RATS

The ventral pallidum (VP) is a major basal forebrain structure implicated in motivation and affect, yet the functional organization of genetically defined VP neurons remains poorly understood. Here, we investigated how Dlx-expressing GABAergic VP neurons and their projection-specific outputs regulate locomotion, anxiety-like behavior, and social interaction in adult rats. We combined viral tract tracing, immunohistochemistry, chemogenetic inhibition, and projection-specific optogenetic activation. Retrograde labeling from downstream targets was quantified by assessing its overlap with viral expression in the VP, and the cellular composition of labeled neurons was characterized by examining co-expression with calcium-binding proteins. Chemogenetic inhibition of Dlx-expressing VP neurons markedly reduced locomotion in the open field and decreased open-arm exploration in the elevated plus maze, indicating anxiety-like avoidance. In contrast, assessment of behavioral despair in the forced swim test did not differ between the groups, suggesting that reduced activity reflected changes specifcially in motivational and anxiety-related processes. Inhibition of Dlx-expressing VP neurons also produced robust social avoidance and impaired contextual fear encoding, as indicated by reduced freezing during context extinction. Optogenetic activation of Dlx-expressing VP projections yielded pathway-specific effects on social behavior, with increased social approach following axonal stimulation in the lateral habenula and increased social avoidance following stimulation in the ventral tegmental area. Together, these findings identify Dlx-expressing GABAergic VP neurons as critical regulators of motivational state and anxiety-related behavior, contributing to opposing behavioral outcomes through distinct projections to the lateral habenula and ventral tegmental area.