Characterizing the role of ventral pallidal astrocytes in approach/avoidance conflict

Project Summary Many research groups concentrate on elucidating the substrates underlying reward-seeking behaviors or avoidance behaviors, resulting in a wealth of datasets detailing neuronal circuits governing motivation. However, the dynamics of opposing motivational circuits operating during approach/avoidance conflicts remain poorly understood. This knowledge gap is significant, as compromised approach/avoidance behaviors are hallmark features of anxiety, depression, and addiction. The nucleus accumbens (NAc) and the ventral pallidum (VP) are key mediators of approach/avoidance conflict. Nevertheless, we know little of how NAc-VP synapses regulate approach/avoidance conflict. Furthermore, despite a wealth of data demonstrating the pivotal role of astrocytes in regulating synapses, our understanding of their impact on synapses regulating approach/avoidance behavior is nil. Here, we propose to characterize the role of VP astrocytes in influencing approach/avoidance conflict behaviors in mice, using fiber photometry and chemogenetic manipulations in the platform-mediated avoidance task. In Aim 1, we will characterize the activity of VP astrocytes in approach/avoidance conflict using fiber photometry and immunolabeling. In Aim 2, we will probe the role of VP astrocytes in approach/avoidance conflict using optogenetic perturbation and hPMCA2w/b-mediated calcium extrusion to explore the role of VP astrocytes in approach/avoidance conflict in the platform-mediated avoidance task. Findings from this work will shed light on how astrocytes mediate approach/avoidance conflict by regulating key synapses.