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Regulation of main olfactory bulb mitral cell excitability by metabotropic glutamate receptor mGluR1

Thomas Heinbockel1, Philip Heyward, François Conquet

  • 1Department of Physiology and Program Neuroscience, University of Maryland School of Medicine, 655 W. Baltimore St., Baltimore, MD 21201, USA. thein001@umaryland.edu

Journal of Neurophysiology
|June 24, 2004
PubMed

Insights

Group I metabotropic glutamate receptor 1 (mGluR1) directly excites mitral cells in the olfactory bulb. This receptor regulates neuronal excitability and sensory responses in the main olfactory bulb.

Area of Science:

  • Neuroscience
  • Olfactory System Physiology
  • Receptor Pharmacology

Background:

  • Mitral cells (MCs) in the rodent main olfactory bulb (MOB) express high levels of group I metabotropic glutamate receptor 1 (mGluR1).
  • The precise physiological role of mGluR1 in modulating MC excitability remains largely unknown.

Purpose of the Study:

  • To investigate the physiological role of mGluR1 in regulating MC activity within the rat and mouse MOB.
  • To determine if mGluR1 directly influences MC excitability and responses to olfactory nerve input.

Main Methods:

  • Electrophysiological recordings (voltage-clamp and current-clamp) in MOB slices from wild-type, mGluR1 knockout, and mGluR5 knockout mice.
  • Application of selective group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) and various mGluR antagonists (LY341495, MCPG, LY367385).
  • Assessment of MC responses to DHPG, spontaneous activity, and olfactory nerve stimulation under pharmacological blockade of fast synaptic transmission.

Main Results:

  • DHPG induced direct, voltage-dependent depolarization and increased firing in MCs, effects mediated by potassium and calcium channels.
  • DHPG-induced excitation was absent in mGluR1 knockout mice, confirming the specific role of mGluR1.
  • mGluR1 antagonists modulated MC spontaneous activity, altered membrane potential bistability, and attenuated responses to olfactory nerve input.

Conclusions:

  • Group I mGluR1 directly activates MCs, contributing to their intrinsic excitability.
  • Endogenous glutamate tonically modulates MC excitability and sensory processing in the MOB via mGluR1 activation.
  • mGluR1 plays a critical role in regulating the overall function of the main olfactory bulb circuitry.

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