cardiovascular-agents and linopirdine

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.

Topics: Animals; Biological Clocks; Cardiovascular Agents; Cation Transport Proteins; Cyclic AMP-Dependent Protein Kinases; Hippocampus; Immunohistochemistry; Indoles; Interneurons; Ion Channels; Membrane Potentials; Mice; Mice, Knockout; Muscarine; Muscarinic Agonists; Nerve Net; Potassium Channel Blockers; Pyramidal Cells; Pyridines; Pyrimidines; Receptor, Muscarinic M1; Receptors, Muscarinic; Synaptic Transmission