title: Muscarine-induced increase in frequency of spontaneous EPSCs in Purkinje cells in the vestibulo-cerebellum of the rat.
abstract: Cholinergic projections are relatively sparse in the cerebellum compared with other parts of the brain. However, some mossy fibers in the vestibulo-cerebellum are known to be cholinergic. To clarify the functional roles of cholinergic mossy fibers in the vestibulo-cerebellum, we investigated the effects of acetylcholine (ACh) on the membrane electrical properties of both granule cells and Purkinje cells in slices of the cerebellar vermis of the rat using whole-cell patch-clamp techniques. The bath application of ACh induced a marked increase in the frequency of spontaneous EPSCs (sEPSCs) in Purkinje cells specifically in the vestibulo-cerebellum. This effect of ACh was mimicked by muscarine but not by nicotine. It was abolished by application of either tetrodotoxin or the antagonist of AMPA receptors, indicating that the ACh-induced enhancement of sEPSCs occurred indirectly via the activation of neurons sending glutamatergic projections to Purkinje cells. In approximately 15% of granule cells tested in the vestibulo-cerebellum, muscarine elicited membrane depolarization accompanied by a decrease in membrane conductance and increased the neuronal excitability. The muscarine-induced depolarization of granule cells in the vestibulo-cerebellum was attributable to the inhibition of standing-outward K+ currents (IKSO) most likely via the activation of muscarinic M3 receptors. Taken together, these results indicate that ACh increases the firing frequency of granule cells by inhibiting IKSO, which in turn increases the frequency of sEPSCs in Purkinje cells in the rat vestibulo-cerebellum.
authors.affiliation: Department of Physiology, Gunma University School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takayasu
authors.forename: Masae
authors.initials: M
authors.lastname: Iino
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Furuya
authors.forename: Seiji
authors.initials: S
authors.lastname: Ozawa
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018678:Cholinergic Agents / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009116:Muscarine / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism
chemical_list: D018678:Cholinergic Agents; D018721:Muscarinic Agonists; D018722:Nicotinic Agonists; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D009116:Muscarine; D000109:Acetylcholine; D011188:Potassium