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

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NATURE COMMUNICATIONS
卷 14, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41467-023-39545-8

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The authors found that GPe arky neurons are involved in reward-seeking behaviors and primarily project to the dorsolateral striatum. Genetic ablation of this circuit shift behavior from goal-directed to habitual seeking.
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 arky(GPe & RARR;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 arky(GPe & RARR;DLS) circuit in constraining habitual seeking in male mice, which is relevant to addictive behaviors and other compulsive disorders. The external part of the globus pallidus is involved in action-selection. Here, the authors investigate the function of an arkypallidal neuronal circuit to the dorsolateral striatum in goal-directed and habitual-seeking behaviors in male mice.

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