| First Author | Tian G | Year | 2024 |
| Journal | Neuron | PubMed ID | 39153478 |
| Mgi Jnum | J:353811 | Mgi Id | MGI:7717305 |
| Doi | 10.1016/j.neuron.2024.07.018 | Citation | Tian G, et al. (2024) Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity. Neuron |
| abstractText | The globus pallidus externus (GPe) is a central component of the basal ganglia circuit that acts as a gatekeeper of cocaine-induced behavioral plasticity. However, the molecular and circuit mechanisms underlying this function are unknown. Here, we show that GPe parvalbumin-positive (GPe(PV)) cells mediate cocaine responses by selectively modulating ventral tegmental area dopamine (VTA(DA)) cells projecting to the dorsomedial striatum (DMS). Interestingly, GPe(PV) cell activity in cocaine-naive mice is correlated with behavioral responses following cocaine, effectively predicting cocaine sensitivity. Expression of the voltage-gated potassium channels KCNQ3 and KCNQ5 that control intrinsic cellular excitability following cocaine was downregulated, contributing to the elevation in GPe(PV) cell excitability. Acutely activating channels containing KCNQ3 and/or KCNQ5 using the small molecule carnosic acid, a key psychoactive component of Salvia rosmarinus (rosemary) extract, reduced GPe(PV) cell excitability and impaired cocaine reward, sensitization, and volitional cocaine intake, indicating its therapeutic potential to counteract psychostimulant use disorder. |
