ArticleJournal of neurophysiology2011
M1 and M4 receptors modulate hippocampal pyramidal neurons.
Article in Journal of neurophysiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.
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Who cites it
83 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- Cholinergic system in schizophrenia: A systematic review and meta-analysis.Molecular psychiatry · 2025Pooled it
- Article
- Cholinergic modulation of hippocampal CA1 pyramidal cell excitability in ArxExperimental neurology · 2026Article
- Targeting muscarinic receptors for treating schizophrenia.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- The mechanism of action and clinical efficacy of xanomeline-trospium in schizophrenia: A comprehensive review.Therapeutic advances in psychopharmacology · 2026Review
- Modulation of speed-dependent acetylcholine release in the hippocampus by spatial task engagement.Cell reports · 2025Article
- Modeling presynaptic inhibition by the amyloid precursor protein demonstrates one potential mechanism for preventing runaway synaptic modification in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- REM sleep prefrontal ripple chains mediate distinct cortical-hippocampal reactivation patterns compared to NREM ripples.bioRxiv : the preprint server for biology · 2025Article
- Afferent-specific modulation of excitatory synaptic transmission by acetylcholine and serotonin in the prelimbic cortex.bioRxiv : the preprint server for biology · 2025Article
- Cholinergic modulation of neural networks supports sequential and complementary roles for NREM and REM states in memory consolidation.PLoS computational biology · 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
- Development of the SPEAR Model: Separate Phases of Encoding and Retrieval Are Necessary for Storing Multiple Overlapping Associative Memories.Hippocampus · 2025Review
- Acetylcholine in the hippocampus: problems and achievements.Frontiers in neural circuits · 2025Review
- Huperzine A suppresses absence seizures in the genetic absence epilepsy rat from Strasbourg (GAERS) model of genetic generalized epilepsy with absence seizures.Epilepsia open · 2024Article
- Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.Clinical drug investigation · 2024Review
- Septohippocampal cholinergic system at the intersection of stress and cognition: Current trends and translational implications.The European journal of neuroscience · 2024Review
- Accelerated neurodegeneration of basal forebrain cholinergic neurons in HIV-1 gp120 transgenic mice: Critical role of the p75 neurotrophin receptor.Brain, behavior, and immunity · 2024Article
- Cholinergic Activation of Corticofugal Circuits in the Adult Mouse Prefrontal Cortex.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Muscarinic Modulation of Network Excitability and Short-Term Dynamics in the Dorsal and Ventral Hippocampus.microPublication biology · 2024Article
- The potential of muscarinic MFrontiers in psychiatry · 2024Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Acetylcholine (ACh), acting at muscarinic ACh receptors (mAChRs), modulates the excitability and synaptic connectivity of hippocampal pyramidal neurons. CA1 pyramidal neurons respond to transient ("phasic") mAChR activation with biphasic responses in which inhibition is followed by excitation, whereas prolonged ("tonic") mAChR activation increases CA1 neuron excitability. Both phasic and tonic mAChR activation excites pyramidal neurons in the CA3 region, yet ACh suppresses glutamate release at the CA3-to-CA1 synapse (the Schaffer-collateral pathway). Using mice genetically lacking specific mAChRs (mAChR knockout mice), we identified the mAChR subtypes responsible for cholinergic modulation of hippocampal pyramidal neuron excitability and synaptic transmission. Knockout of M1 receptors significantly reduced, or eliminated, most phasic and tonic cholinergic responses in CA1 and CA3 pyramidal neurons. On the other hand, in the absence of other G(q)-linked mAChRs (M3 and M5), M1 receptors proved sufficient for all postsynaptic cholinergic effects on CA1 and CA3 pyramidal neuron excitability. M3 receptors were able to participate in tonic depolarization of CA1 neurons, but otherwise contributed little to cholinergic responses. At the Schaffer-collateral synapse, bath application of the cholinergic agonist carbachol suppressed stratum radiatum-evoked excitatory postsynaptic potentials (EPSPs) in wild-type CA1 neurons and in CA1 neurons from mice lacking M1 or M2 receptors. However, Schaffer-collateral EPSPs were not significantly suppressed by carbachol in neurons lacking M4 receptors. We therefore conclude that M1 and M4 receptors are the major mAChR subtypes responsible for direct cholinergic modulation of the excitatory hippocampal circuit.
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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.