External globus pallidus input to the dorsal striatum regulates habitual seeking behavior in male mice

外部苍白球输入至背侧纹状体调节雄性小鼠的习惯性寻求行为

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作者:Matthew Baker #, Seungwoo Kang #, Sa-Ik Hong, Minryung Song, Minsu Abel Yang, Lee Peyton, Hesham Essa, Sang Wan Lee, Doo-Sup Choi

Abstract

The external globus pallidus (GPe) coordinates action-selection through GABAergic projections throughout the basal ganglia. GPe arkypallidal (arky) neurons project exclusively to the dorsal striatum, which regulates goal-directed and habitual seeking. However, the role of GPe arky neurons in reward-seeking remains unknown. Here, we identified that a majority of arky neurons target the dorsolateral striatum (DLS). Using fiber photometry, we found that arky activities were higher during random interval (RI; habit) compared to random ratio (RR; goal) operant conditioning. Support vector machine analysis demonstrated that arky neuron activities have sufficient information to distinguish between RR and RI behavior. Genetic ablation of this arkyGPe→DLS circuit facilitated a shift from goal-directed to habitual behavior. Conversely, chemogenetic activation globally reduced seeking behaviors, which was blocked by systemic D1R agonism. Our findings reveal a role of this arkyGPe→DLS circuit in constraining habitual seeking in male mice, which is relevant to addictive behaviors and other compulsive disorders.

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