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.

Grant Number: 1R21MH137593-01A1
NIH Institute/Center: NIH
Principal Investigator: Christian Bravo-Rivera