title: Modulation of synaptic plasticity by physiological activation of M1 muscarinic acetylcholine receptors in the mouse hippocampus.
abstract: The muscarinic acetylcholine receptor (mAChR) has been considered one of the neurotransmitter receptors regulating hippocampal synaptic plasticity, which likely plays a critical role in learning and memory. In previous studies, however, muscarinic agonists were used at relatively high concentrations, and the subtype selectivity of muscarinic antagonists was not satisfactory. Thus, it remains to be answered whether physiological levels of ACh are involved in the regulation of synaptic plasticity and which mAChR subtypes are responsible for such effects. We found in this study that a low concentration (50 nM) of carbachol enhanced long-term potentiation (LTP) of excitatory synaptic transmission in mouse hippocampal slices. Notably, this enhancing effect was abolished in M1 mAChR knock-out (KO) but not in M3 mAChR KO mice, although LTP itself was intact in both mutant mice. Furthermore, we found that repetitive stimulation in the stratum oriens, which presumably triggered the release of endogenous ACh from cholinergic terminals, could enhance LTP in wild-type mice but not in M1 mAChR KO mice. These results suggest that physiologically released ACh from cholinergic fibers modulates hippocampal synaptic plasticity through the postsynaptic M1 mAChR activation.
authors.affiliation: Division of Neuronal Network, Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Shinoe
authors.forename: Minoru
authors.initials: M
authors.lastname: Matsui
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Toshiya
authors.initials: T
authors.lastname: Manabe
mesh_terms: D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D006624:Hippocampus / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D043643:Receptor, Muscarinic M1 / Q000172:deficiency / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D018679:Cholinergic Agonists; D043643:Receptor, Muscarinic M1; D002217:Carbachol; D000109:Acetylcholine