Noradrenergic modulation of synaptic transmission between olfactory bulb neurons in culture: implications to olfactory learning.
Noradrenergic modulation of the glutamatergic-GABAergic synapses between mitral/tufted (M/T) and granule cells has been implicated in some forms of olfactory learning (5), but the mechanism of action is unknown. Intracellular stimulation of M/T cells in primary culture, evoked glutamate-mediated excitatory postsynaptic potentials (EPSPs) in granule cells that were reversibly inhibited by approximately 50% during application of norepinephrine (NE). NE had no effect, however, on the membrane current evoked by the application of glutamate, indicating a presynaptic site of action. The effect of NE on EPSPs was mimicked by the alpha receptor agonist clonidine, but not by the beta receptor agonist isoproteronol. NE also inhibited spontaneous GABAergic inhibitory postsynaptic potentials recorded in M/T cells, by a presynaptic alpha-adrenergic mediated mechanism. NE and clonidine also inhibited high threshold calcium currents. The effects of NE on calcium currents were irreversible in the presence of internal GTP gamma S and prevented by pertussis toxin, suggesting a G protein-coupled mechanism. Pertussis toxin also prevented the effects of NE on synaptic transmission. These results support previous results suggesting a disinhibitory role for NE in the olfactory bulb. This action is, at least in part, due to a reduction in mitral cell mediated granule cell excitation through inhibition of presynaptic calcium influx.
Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510.
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D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology; D007858:Learning / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology / Q000502:physiology*; D037342:Pertussis Toxin; D051381:Rats; D012903:Smell / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D018691:Excitatory Amino Acid Antagonists; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009638:Norepinephrine