Chronic alcohol induces subcircuit-specific striatonigral plasticity enhancing the sensorimotor basal ganglia role in action execution

慢性酒精会诱导纹状体黑质通路特定亚回路的可塑性,从而增强感觉运动基底神经节在动作执行中的作用。

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作者:Giacomo Sitzia ,Sebastiano Bariselli ,Alexa Gracias ,David M Lovinger

Abstract

Functional deficits in basal ganglia (BG) circuits contribute to cognitive and motor dysfunctions in alcohol use disorder. Chronic alcohol exposure alters synaptic function and neuronal excitability in the dorsal striatum, but it remains unclear how it affects BG output that is mediated by the substantia nigra pars reticulata (SNr). Here, we describe a neuronal subpopulation-specific synaptic organization of striatal and subthalamic (STN) inputs to the medial and lateral SNr. Chronic alcohol exposure (CIE) potentiated dorsolateral striatum (DLS) inputs but did not change dorsomedial striatum and STN inputs to the SNr. Chemogenetic inhibition of DLS direct pathway neurons revealed an enhanced role for DLS direct pathway neurons in execution of an instrumental lever-pressing task. Overall, we reveal a subregion-specific organization of striatal and subthalamic inputs onto the medial and lateral SNr and find that potentiated DLS-SNr inputs are accompanied by altered BG control of action execution following CIE.

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