title: Muscarinic induction of hippocampal gamma oscillations requires coupling of the M1 receptor to two mixed cation currents.
abstract: Oscillatory network activity at gamma frequencies is assumed to be of major importance in cortical information processing. Whereas the synaptic mechanisms of gamma oscillations have been studied in detail, the ionic currents involved at the cellular level remain to be elucidated. Here we show that in vitro gamma oscillations induced by muscarine require activation of M1 receptors on hippocampal CA3 pyramidal neurons and are absent in M1 receptor-deficient mice. M1 receptor activation depolarizes pyramidal neurons by increasing the mixed Na(+)/K(+) current I(h) and the Ca(2+)-dependent nonspecific cation current I(cat), but not by modulation of I(M). Our data provide important insight into the molecular basis of gamma oscillations by unequivocally establishing a novel role for muscarinic modulation of I(h) and I(cat) in rhythmic network activity.
authors.affiliation: Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
authors.forename: André
authors.initials: A
authors.lastname: Fisahn
authors.forename: Masahisa
authors.initials: M
authors.lastname: Yamada
authors.forename: Alokesh
authors.initials: A
authors.lastname: Duttaroy
authors.forename: Jai-Wei
authors.initials: JW
authors.lastname: Gan
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
authors.forename: Chris J
authors.initials: CJ
authors.lastname: McBain
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wess
mesh_terms: D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002317:Cardiovascular Agents / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic / Q000172:deficiency* / Q000187:drug effects / Q000235:genetics; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002317:Cardiovascular Agents; D027682:Cation Transport Proteins; D007211:Indoles; D007473:Ion Channels; D018721:Muscarinic Agonists; D026902:Potassium Channel Blockers; D011725:Pyridines; D011743:Pyrimidines; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic; C082246:ICI D2788; D009116:Muscarine; D017868:Cyclic AMP-Dependent Protein Kinases; C061017:linopirdine