ArticleNature communications2023
Drug reinforcement impairs cognitive flexibility by inhibiting striatal cholinergic neurons.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Nitrous oxide controls the DCN to VTA dopamine circuit by enhancing AMPA receptor functions during rewarding behavior.Molecular psychiatry · 2026Article
- Acquisition-Recruited and MOR-Expressing Striatal dMSNs Differentially Regulate Extinction and Cue-Induced Relapse of Alcohol Seeking.Addiction biology · 2026Article
- Spatiomolecular mapping reveals anatomical organization of heterogeneous cell types in the human nucleus accumbens.Neuron · 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
- Subregion-Specific Input Organization of Prefrontal-Projecting Basal Forebrain Cholinergic Neurons and Weakened Striatal-NBM Inhibitory Transmission in 5xFAD mice.bioRxiv : the preprint server for biology · 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
- Striatal Acetylcholine Dip-Rebound Is Induced by Direct-Pathway Neurons and Encode Action-Outcome Contingency.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
- Dual Engram Architecture within a Single Striatal Cell Type Distinctly Controls Alcohol Relapse and Extinction.bioRxiv : the preprint server for biology · 2026Article
- Regional heterogeneity of striatal cholinergic interneurons: setting the stage for diverse behavioral repertoires.Frontiers in cellular neuroscience · 2026Review
- Alcohol Attenuates CRF-Induced Excitatory Effects from the Extended Amygdala to Dorsostriatal Cholinergic Interneurons.bioRxiv : the preprint server for biology · 2025Article
- Prosapip1 (encoded by theeLife · 2025Article
- 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
- Cholinergic interneurons of the dorsomedial striatum mediate winner-loser effects on social hierarchy dynamics in male mice.iScience · 2025Article
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Authors and funding
13 authors.
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Abstract
Addictive substance use impairs cognitive flexibility, with unclear underlying mechanisms. The reinforcement of substance use is mediated by the striatal direct-pathway medium spiny neurons (dMSNs) that project to the substantia nigra pars reticulata (SNr). Cognitive flexibility is mediated by striatal cholinergic interneurons (CINs), which receive extensive striatal inhibition. Here, we hypothesized that increased dMSN activity induced by substance use inhibits CINs, reducing cognitive flexibility. We found that cocaine administration in rodents caused long-lasting potentiation of local inhibitory dMSN-to-CIN transmission and decreased CIN firing in the dorsomedial striatum (DMS), a brain region critical for cognitive flexibility. Moreover, chemogenetic and time-locked optogenetic inhibition of DMS CINs suppressed flexibility of goal-directed behavior in instrumental reversal learning tasks. Notably, rabies-mediated tracing and physiological studies showed that SNr-projecting dMSNs, which mediate reinforcement, sent axonal collaterals to inhibit DMS CINs, which mediate flexibility. Our findings demonstrate that the local inhibitory dMSN-to-CIN circuit mediates the reinforcement-induced deficits in cognitive flexibility.
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