ArticleThe Journal of physiology2014
Direct excitation of parvalbumin-positive interneurons by M1 muscarinic acetylcholine receptors: roles in cellular excitability, inhibitory transmission and cognition.
Article in The Journal of physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 121 citations in OpenAlex.
- Xanomeline-Trospium Validates Muscarinic Agonism as an Effective Non-Dopaminergic Treatment for Schizophrenia.International journal of molecular sciences · 2026Review
- M1 receptor modulator VU0364572 attenuates cortico-thalamo-striatal transmission and facilitates cocaine CPP extinction.Cellular and molecular life sciences : CMLS · 2026Article
- The mechanism of action and clinical efficacy of xanomeline-trospium in schizophrenia: A comprehensive review.Therapeutic advances in psychopharmacology · 2026Review
- Targeting muscarinic receptors for treating schizophrenia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Perinatal mAChR-mediated activation of cortical subplate neurons elicits network activity driving basket cell differentiation.Frontiers in cellular neuroscience · 2026Article
- Clozapine induces perineuronal net remodeling in a developmental mouse model exhibiting schizophrenia-relevant phenotypes.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Targeting disrupted networks in schizophrenia: Can muscarinic drugs make a fundamental difference?Journal of psychopharmacology (Oxford, England) · 2025Review
- Cholinergic modulation of neural networks supports sequential and complementary roles for NREM and REM states in memory consolidation.PLoS computational biology · 2025Article
- Increased excitability of dentate gyrus mossy cells occurs early in life in the Tg2576 model of Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- From theory to therapy: unlocking the potential of muscarinic receptor activation in schizophrenia with the dual M1/M4 muscarinic receptor agonist xanomeline and trospium chloride and insights from clinical trials.The international journal of neuropsychopharmacology · 2025Review
- Alteration of hippocampal parvalbumin interneurons underlies memory impairment in rat model of Parkinson's disease.Frontiers in behavioral neuroscience · 2025Article
- Discovering functional interactions among schizophrenia-risk genes by combining behavioral genetics with cell biology.Neuroscience and biobehavioral reviews · 2024Review
- The excitatory-inhibitory balance as a target for the development of novel drugs to treat schizophrenia.Biochemical pharmacology · 2024Review
- Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.Clinical drug investigation · 2024Review
- Inhibition of cortical synaptic transmission, behavioral nociceptive, and anxiodepressive-like responses by arecoline in adult mice.Molecular brain · 2024Article
- Conditioning and pseudoconditioning differently change intrinsic excitability of inhibitory interneurons in the neocortex.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- The potential of muscarinic MFrontiers in psychiatry · 2024Review
- Dialectics of perisomatic inhibition-The unity and conflict of opposites.Frontiers in neural circuits · 2024Review
- Muscarinic Modulation of Network Excitability and Short-Term Dynamics in the Dorsal and Ventral Hippocampus.microPublication biology · 2024Article
- Cognitive impairment in schizophrenia: aetiology, pathophysiology, and treatment.Molecular psychiatry · 2023Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Parvalbumin-containing (PV) neurons, a major class of GABAergic interneurons, are essential circuit elements of learning networks. As levels of acetylcholine rise during active learning tasks, PV neurons become increasingly engaged in network dynamics. Conversely, impairment of either cholinergic or PV interneuron function induces learning deficits. Here, we examined PV interneurons in hippocampus (HC) and prefrontal cortex (PFC) and their modulation by muscarinic acetylcholine receptors (mAChRs). HC PV cells, visualized by crossing PV-CRE mice with Rosa26YFP mice, were anatomically identified as basket cells and PV bistratified cells in the stratum pyramidale; in stratum oriens, HC PV cells were electrophysiologically distinct from somatostatin-containing cells. With glutamatergic transmission pharmacologically blocked, mAChR activation enhanced PV cell excitability in both CA1 HC and PFC; however, CA1 HC PV cells exhibited a stronger postsynaptic depolarization than PFC PV cells. To delete M1 mAChRs genetically from PV interneurons, we created PV-M1 knockout mice by crossing PV-CRE and floxed M1 mice. The elimination of M1 mAChRs from PV cells diminished M1 mAChR immunoreactivity and muscarinic excitation of HC PV cells. Selective cholinergic activation of HC PV interneurons using Designer Receptors Exclusively Activated by Designer Drugs technology enhanced the frequency and amplitude of inhibitory synaptic currents in CA1 pyramidal cells. Finally, relative to wild-type controls, PV-M1 knockout mice exhibited impaired novel object recognition and, to a lesser extent, impaired spatial working memory, but reference memory remained intact. Therefore, the direct activation of M1 mAChRs on PV cells contributes to some forms of learning and memory.
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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.