Muscarinic induction of hippocampal gamma oscillations requires coupling of the M1 receptor to two mixed cation currents

Neuron. 2002 Feb 14;33(4):615-24. doi: 10.1016/s0896-6273(02)00587-1.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • 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
  • 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
  • Mice
  • Mice, Knockout
  • Muscarine / pharmacology
  • Muscarinic Agonists / pharmacology
  • Nerve Net / cytology
  • Nerve Net / drug effects
  • Nerve Net / metabolism*
  • 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
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Cardiovascular Agents
  • Cation Transport Proteins
  • Indoles
  • Ion Channels
  • Muscarinic Agonists
  • Potassium Channel Blockers
  • Pyridines
  • Pyrimidines
  • Receptor, Muscarinic M1
  • Receptors, Muscarinic
  • ICI D2788
  • Muscarine
  • Cyclic AMP-Dependent Protein Kinases
  • linopirdine