ArticleThe Journal of clinical investigation2022
Chronic alcohol drinking persistently suppresses thalamostriatal excitation of cholinergic neurons to impair cognitive flexibility.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Bad habits-good goals? Meta-analysis and translation of the habit construct to alcoholism.Translational psychiatry · 2024Pooled it
- Acquisition-Recruited and MOR-Expressing Striatal dMSNs Differentially Regulate Extinction and Cue-Induced Relapse of Alcohol Seeking.Addiction biology · 2026Article
- Extended Amygdala CRF Projections to Striatal Striosomes Potentiate Dopamine Suppression During Fentanyl Withdrawal.bioRxiv : the preprint server for biology · 2026Article
- Early-Stage Corticostriatal Hyperactivity Impairs Cognitive Flexibility Alongside Striatal Cholinergic Dysfunction in an Alzheimer's Disease Model.Nature communications · 2026Article
- Dual-engram architecture within a single striatal cell type distinctly controls alcohol relapse and extinction.Neuron · 2026Article
- The GPCR Smoothened on cholinergic interneurons modulates dopamine-associated acetylcholine dynamics, learning, and effort management.iScience · 2026Article
- Extinction Training Suppresses Alcohol Relapse by Inhibiting Acquisition-Recruited Striatal Ensembles and Engaging Striosomal Neurons.bioRxiv : the preprint server for biology · 2026Article
- Alcohol and Opioids Modulate Excitatory Inputs to the SCN.bioRxiv : the preprint server for biology · 2026Article
- Article
- Chronic ethanol self-administration alters dopamine in the caudate nucleus and putamen of rhesus macaques in a sex-dependent manner.bioRxiv : the preprint server for biology · 2026Article
- Dual Engram Architecture within a Single Striatal Cell Type Distinctly Controls Alcohol Relapse and Extinction.bioRxiv : the preprint server for biology · 2026Article
- Early-Stage Corticostriatal Circuit Hyperactivity Impairs Cholinergic Function and Cognitive Flexibility in an Alzheimer's Model.bioRxiv : the preprint server for biology · 2026Article
- Neurotoxic effects of chronic ethanol on cholinergic interneurons in the dorsomedial striatum.Neuropharmacology · 2026Article
- Alcohol Attenuates CRF-Induced Excitatory Effects from the Extended Amygdala to Dorsostriatal Cholinergic Interneurons.bioRxiv : the preprint server for biology · 2025Article
- Cognitive training shapes brain plasticity and schematic representations.Behavioral and brain functions : BBF · 2025Review
- Abstinence and extinction drive opposing changes in striatal activity and dopamine signaling during alcohol relapse.Neuropharmacology · 2025Article
- Perinatal and prenatal alcohol exposure impairs striatal cholinergic function and cognitive flexibility in adult offspring.Neuropharmacology · 2025Article
- Traumatic brain injury exacerbates alcohol consumption and neuroinflammation with decline in cognition and cholinergic activity.Translational psychiatry · 2025Article
- Alcohol effects on associative and sensorimotor cortico-thalamo-basal ganglia circuits alter decision making and alcohol intake.Alcohol (Fayetteville, N.Y.) · 2025Review
- Pathology-Specific Modulation of Corticostriatal Circuitry by Chronic Alcohol Consumption in Alzheimer's Disease Mouse Models.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.