open access publication

Article, 2024

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

Science Advances, ISSN 2375-2548, Volume 10, 26, Page eadm6951, 10.1126/sciadv.adm6951

Contributors

Sitzia, Giacomo 0000-0003-2244-4393 [1] [2] Bariselli, Sebastiano 0000-0003-3483-3169 [2] [3] Gracias, Alexa L [2] Lovinger, David M (Corresponding author) [2]

Affiliations

  1. [1] University of Copenhagen
    2. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  2. [2] National Institute on Alcohol Abuse and Alcoholism
    3. [NORA names: United States; America, North; OECD];
  3. [3] IRCCS Humanitas Research Hospital
    4. [NORA names: Italy; Europe, EU; OECD]

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.

Keywords

BG control, BG output, STN, action, action execution, alcohol, alcohol exposure, alcohol use disorder, basal ganglia, basal ganglia role, chemogenetic inhibition, chronic alcohol exposure, chronic alcoholism, circuit, control, deficits, direct pathway neurons, disorders, dorsal striatum, dorsolateral striatum, dorsomedial striatum, dysfunction, enhanced role, excitation, execution, exposure, function, functional deficits, ganglia, input, lateral substantia nigra pars reticulata, lever-pressing task, motor, motor dysfunction, neuronal excitability, neurons, nigra pars reticulata, organization, output, pars reticulata, pathway neurons, plasticity, reticulata, role, sensorimotor, striatum, substantia, substantia nigra pars reticulata, subthalamic inputs, synaptic function, synaptic organization, task, use disorder

Funders

  • National Institute on Alcohol Abuse and Alcoholism

Data Provider: Digital Science

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