M1 Muscarinic Receptors Boost Synaptic Potentials and Calcium Influx in Dendritic Spines by Inhibiting Postsynaptic SK Channels
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Acetylcholine release and activation of muscarinic cholinergic receptors (mAChRs) enhance synaptic plasticity in vitro and cognition and memory in vivo. Within the hippocampus, mAChRs promote NMDA-type glutamate receptor-dependent forms of long-term potentiation. Here, we use calcium (Ca) imaging combined with two-photon laser glutamate uncaging at apical spines of CA1 pyramidal neurons to examine postsynaptic mechanisms of muscarinic modulation of glutamatergic transmission. Uncaging-evoked excitatory postsynaptic potentials and Ca transients are increased by muscarinic stimulation; however, this is not due to direct modulation of glutamate receptors. Instead, mAChRs modulate a negative feedback loop in spines that normally suppresses synaptic signals. mAChR activation reduces the Ca sensitivity of small conductance Ca-activated potassium (SK) channels that are found in the spine, resulting in increased synaptic potentials and Ca transients. These effects are mediated by M1-type muscarinic receptors and occur in a casein kinase-2-dependent manner. Thus, muscarinic modulation regulates synaptic transmission by tuning the activity of nonglutamatergic postsynaptic ion channels.
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mAChRs at excitatory synapses may increase postsynaptic responses.
“mAChRs at excitatory synapses may decrease presynaptic release185 and increase postsynaptic responses186 through independent mechanisms”
From Mechanisms underlying gain modulation in the cortex (2020) · cites this paper as [186]
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- Authors
- Giessel, A. J., & Sabatini, B. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sabatini, Bernardo L.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 68
- Issue
- 5
- Pages
- 936-947
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3052967
- OpenAlex
- W2111550789
- Cited by
- 156
- References
- 62
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 9 · 2021: 10 · 2020: 7 · 2019: 8 · 2018: 13 · 2017: 16 · 2016: 7 · 2015: 11 · 2014: 16 · 2013: 13 · 2012: 20
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R01NS046579, F31NS065647, R37NS046579, NS046579)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- M1 muscarinic receptor, muscarinic receptors, small conductance calcium-activated potassium channels, dendritic spines, excitatory postsynaptic potentials, calcium transients, glutamate uncaging, casein kinase 2, CA1 pyramidal neurons, synaptic plasticity, glutamatergic neurotransmission, negative feedback loop
- MeSH terms
- Acetylcholine, Animals, Calcium, Mice, Inbred C57BL, Second Messenger Systems, Signal Transduction, Pyramidal Cells, Receptor Cross-Talk, Feedback, Physiological, Receptor, Muscarinic M1, Casein Kinase II, Dendritic Spines, Mice, Small-Conductance Calcium-Activated Potassium Channels, Synaptic Potentials, CA1 Region, Hippocampal, In Vitro Techniques
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