Muscarinic induction of hippocampal gamma oscillations requires coupling of the M1 receptor to two mixed cation currents.
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.
Fisahn
André
A
Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892, USA.
Yamada
Masahisa
M
Duttaroy
Alokesh
A
Gan
Jai-Wei
JW
Deng
Chu-Xia
CX
McBain
Chris J
CJ
Wess
Jürgen
J
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
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