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

Matthew Baker, Seungwoo Kang, Sa-Ik Hong, Minryung Song, Minsu Abel Yang, Lee Peyton, Hesham Essa, Sang Wan Lee and Doo-Sup Choi ()
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Matthew Baker: Mayo Clinic
Seungwoo Kang: Mayo Clinic
Sa-Ik Hong: Mayo Clinic
Minryung Song: Korea Advanced Institute of Science and Technology (KAIST)
Minsu Abel Yang: Korea Advanced Institute of Science and Technology (KAIST)
Lee Peyton: Mayo Clinic
Hesham Essa: Mayo Clinic
Sang Wan Lee: Korea Advanced Institute of Science and Technology (KAIST)
Doo-Sup Choi: Mayo Clinic

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39545-8

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