Neuron
Volume 33, Issue 4, 14 February 2002, Pages 615-624
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Article
Muscarinic Induction of Hippocampal Gamma Oscillations Requires Coupling of the M1 Receptor to Two Mixed Cation Currents

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Abstract

Oscillatory network activity at γ frequencies is assumed to be of major importance in cortical information processing. Whereas the synaptic mechanisms of γ oscillations have been studied in detail, the ionic currents involved at the cellular level remain to be elucidated. Here we show that in vitro γ 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 Ih and the Ca2+-dependent nonspecific cation current Icat, but not by modulation of IM. Our data provide important insight into the molecular basis of γ oscillations by unequivocally establishing a novel role for muscarinic modulation of Ih and Icat in rhythmic network activity.

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5

These authors contributed equally to this work.

6

Present address: Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, Saitama 351-0198, Japan.