DIVERSITY OF NICOTINIC ACETYLCHOLINE-RECEPTORS IN RAT-BRAIN .5. ALPHA-BUNGAROTOXIN-SENSITIVE NICOTINIC RECEPTORS IN OLFACTORY-BULB NEURONS AND PRESYNAPTIC MODULATION OF GLUTAMATE RELEASE

The presence of functional nicotinic acetylcholine receptors (nAChRs) on cultured neurons of the rat olfactory bulb was evaluated using the whole-cell patch-clamp technique. Application of acetylcholine (ACh) t o 78% of the tested olfactory bulb neurons evoked whole-cell currents (referred to as direct response), which are very similar in characteri stics to type IA currents. Their peak amplitude increased, while their rise-time and decay-time constants decreased with increasing agonist concentration. In 12% of the neurons, ACh evoked single or multiple mi niature postsynaptic currents (referred to as indirect response) for w hich amplitude, rise time, and decay-time constants were not dependent upon the ACh concentration. Methyllycaconitine (1 nM), a selective co mpetitive antagonist at the the alpha-bungarotoxin-sensitive neuronal nAChR, reversibly blocked both responses, whereas 6-cyano-T-nitroquino xaline-2,3-dione (10 mu M) reversibly blocked only the indirect respon ses. Whereas tetradotoxin (0.2-2 mu M) failed to affect the indirect r esponse, Ca++-free, Mg++-containing external solution decreased revers ibly and significantly the frequency of ACh-evoked miniature postsynap tic currents. The pharmacology and kinetics of the two types of respon ses are consistent with the existence in the olfactory bulb neurons of alpha-bungarotoxin-sensitive nAChRs at both postsynaptic and presynap tic sites, the presynaptic receptors being located on glutamatergic sy napses where they modulate the release of the transmitter. The dimensi ons of the soma and dendrites of the neurons suggest that the direct r esponse is obtained from periglomerular and/or granular neurons, and t he indirect response from short-axon and/or external tufted cells. The present results suggest that 1) nicotinic synaptic transmission could play an important role in modulating the bulbar output at the glomeru lar level, and 2) a presynaptic modulatory effect is one of the functi ons for the alpha-bungarotoxin-sensitive nAChRs in the mammalian centr al nervous system.