NORADRENERGIC MODULATION OF SYNAPTIC TRANSMISSION BETWEEN OLFACTORY-BULB NEURONS IN CULTURE - IMPLICATIONS TO OLFACTORY LEARNING

Noradrenergic modulation of the glutamatergic-GABAergic synapses betwe en mitral/tufted (M/T) and granule cells has been implicated in some f orms of olfactory learning (5), but the mechanism of action is unknown . Intracellular stimulation of M/T cells in primary culture, evoked gl utamate-mediated excitatory postsynaptic potentials (EPSPs) in granule cells that were reversibly inhibited by approximately 50% during appl ication of norepinephrine (NE). NE had no effect, however, on the memb rane current evoked by the application of glutamate, indicating a pres ynaptic 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 pos tsynaptic potentials recorded in M/T cells, by a presynaptic alpha-adr energic mediated mechanism. NE and clonidine also inhibited high thres hold calcium currents. The effects of NE on calcium currents were irre versible in the presence of internal GTP gamma S and prevented by pert ussis toxin, suggesting a G protein-coupled mechanism. Pertussis toxin also prevented the effects of NE on synaptic transmission. These resu lts support previous results suggesting a disinhibitory role for NE in the olfactory bulb. This action is, at least in part, due to a reduct ion in mitral cell mediated granule cell excitation through inhibition of presynaptic calcium influx.