ArticleACS chemical neuroscience2014
M4 mAChR-mediated modulation of glutamatergic transmission at corticostriatal synapses.
Article in ACS chemical neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response.Current neuropharmacology · 2020Pooled it
- Cholinergic interneuron control of GABAergic circuits targeting spiny projection neurons is disrupted in parkinsonian models.bioRxiv : the preprint server for biology · 2026Article
- Dopamine and Acetylcholine in the Striatum: Circuit Interactions and Behavioral Control in Substance Use Disorders.Brain sciences · 2026Review
- Targeting muscarinic receptors for treating schizophrenia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Dorsolateral striatal acetylcholine reorganizes neural ensembles to anticipate threat.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic regulation of cocaine intake through dopaminergic control of cholinergic interneurons in male mice.Nature communications · 2025Article
- Cholinergic neurotransmission in the brain of streptozotocin-induced rat model of sporadic Alzheimer's disease: long-term follow up.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Extrinsic and intrinsic control of striatal cholinergic interneuron activity.Frontiers in molecular neuroscience · 2025Review
- Behavioral signature of trihexyphenidyl in theDystonia (Lausanne, Switzerland) · 2025Article
- Cholinergic System Structure and Function Changes in Individuals with Down Syndrome During the Development of Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Tissue block-resolved developmental transcriptomic atlas of human fetal brainstem reveals gene modules with implications for neurological disorders.Frontiers in cell and developmental biology · 2025Article
- Role of the Central Cholinergic Nervous System in Motor and Non-Motor Symptoms of Parkinson's Disease.Current neuropharmacology · 2025Review
- Activation of MBritish journal of pharmacology · 2024Article
- Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.Clinical drug investigation · 2024Review
- Multiple cholinergic receptor subtypes coordinate dual modulation of acetylcholine on anterior and posterior paraventricular thalamic neurons.Journal of neurochemistry · 2024Article
- Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders.Annual review of pharmacology and toxicology · 2024Review
- Neuromodulator regulation and emotions: insights from the crosstalk of cell signaling.Frontiers in molecular neuroscience · 2024Review
- A sex-specific effect of MFrontiers in molecular neuroscience · 2024Article
- The potential of muscarinic MFrontiers in psychiatry · 2024Review
- The impact of Parkinson's disease on striatal network connectivity and corticostriatal drive: An in silico study.Network neuroscience (Cambridge, Mass.) · 2024Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The striatum is the main input station of the basal ganglia and is extensively involved in the modulation of motivated behavior. The information conveyed to this subcortical structure through glutamatergic projections from the cerebral cortex and thalamus is processed by the activity of several striatal neuromodulatory systems including the cholinergic system. Acetylcholine potently modulates glutamate signaling in the striatum via activation of muscarinic receptors (mAChRs). It is, however, unclear which mAChR subtype is responsible for this modulatory effect. Here, by using electrophysiological, optogenetic, and immunoelectron microscopic approaches in conjunction with a novel, highly selective M4 positive allosteric modulator VU0152100 (ML108) and M4 knockout mice, we show that M4 is a major mAChR subtype mediating the cholinergic inhibition of corticostriatal glutamatergic input on both striatonigral and striatopallidal medium spiny neurons (MSNs). This effect is due to activation of presynaptic M4 receptors, which, in turn, leads to a decrease in glutamate release from corticostriatal terminals. The findings of the present study raise the interesting possibility that M4 mAChR could be a novel therapeutic target for the treatment of neurological and neuropsychiatric disorders involving hyper-glutamatergic transmission at corticostriatal synapses.
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