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Chronic alcohol drinking persistently suppresses thalamostriatal excitation of cholinergic neurons to impair cognitive flexibility. | LitMetric

AI Article Synopsis

  • Chronic alcohol consumption and withdrawal impair the ability to adaptively learn from experiences, specifically in reversing learned behaviors.* -
  • This impairment is linked to a long-lasting decrease in excitatory signals to cholinergic interneurons (CINs) in the dorsomedial striatum, which affects their function in regulating other types of neurons.* -
  • Optogenetic stimulation that enhances the communication between thalamic inputs and CINs can restore some decision-making abilities impaired by chronic alcohol use, shedding light on potential treatments for alcohol use disorder.*

Article Abstract

Exposure to addictive substances impairs flexible decision making. Cognitive flexibility is mediated by striatal cholinergic interneurons (CINs). However, how chronic alcohol drinking alters cognitive flexibility through CINs remains unclear. Here, we report that chronic alcohol consumption and withdrawal impaired reversal of instrumental learning. Chronic alcohol consumption and withdrawal also caused a long-lasting (21 days) reduction of excitatory thalamic inputs onto CINs and reduced pause responses of CINs in the dorsomedial striatum (DMS). CINs are known to inhibit glutamatergic transmission in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) but facilitate this transmission in D2-MSNs, which may contribute to flexible behavior. We discovered that chronic alcohol drinking impaired CIN-mediated inhibition in D1-MSNs and facilitation in D2-MSNs. Importantly, in vivo optogenetic induction of long-term potentiation of thalamostriatal transmission in DMS CINs rescued alcohol-induced reversal learning deficits. These results demonstrate that chronic alcohol drinking reduces thalamic excitation of DMS CINs, compromising their regulation of glutamatergic transmission in MSNs, which may contribute to alcohol-induced impairment of cognitive flexibility. These findings provide a neural mechanism underlying inflexible drinking in alcohol use disorder.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8843706PMC
http://dx.doi.org/10.1172/JCI154969DOI Listing

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