Muscarinic Induction of Hippocampal Gamma Oscillations Requires Coupling of the M1 Receptor to Two Mixed Cation Currents

• Published in: Neuron (Cambridge, Mass.) Mass.), 2002-02, Vol.33 (4), p.615-624
• Main Authors: Fisahn, André, Yamada, Masahisa, Duttaroy, Alokesh, Gan, Jai-Wei, Deng, Chu-Xia, McBain, Chris J, Wess, Jürgen
• Format: Article
• Language: English
• Subjects: Animals; Binding sites; Biological Clocks - drug effects; Biological Clocks - physiology; Cardiovascular Agents - pharmacology; Cation Transport Proteins - drug effects; Cation Transport Proteins - metabolism; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Fourier transforms; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - metabolism; Immunohistochemistry; Indoles - pharmacology; Interneurons - cytology; Interneurons - drug effects; Interneurons - metabolism; Ion Channels - drug effects; Ion Channels - metabolism; Membrane Potentials - drug effects; Membrane Potentials - physiology; Memory; Mice; Mice, Knockout; Muscarine - pharmacology; Muscarinic Agonists - pharmacology; Nerve Net - cytology; Nerve Net - drug effects; Nerve Net - metabolism; Potassium; Potassium Channel Blockers - pharmacology; Pyramidal Cells - cytology; Pyramidal Cells - drug effects; Pyramidal Cells - metabolism; Pyridines - pharmacology; Pyrimidines - pharmacology; Receptor, Muscarinic M1; Receptors, Muscarinic - deficiency; Receptors, Muscarinic - drug effects; Receptors, Muscarinic - genetics; Rodents; Scholarships & fellowships; Software; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(02)00587-1

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 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 γ oscillations by unequivocally establishing a novel role for muscarinic modulation of I h and I cat in rhythmic network activity.