NICOTINIC STIMULATION PRODUCES MULTIPLE FORMS OF INCREASED GLUTAMATERGIC SYNAPTIC TRANSMISSION

Synaptic modulation and long-term synaptic changes are thought to be t he cellular correlates for learning and memory (Madison et al., 1991; Aiba et at., 1994; Goda and Stevens, 1996). The hippocampus is a cente r for learning and memory that receives abundant cholinergic innervati on and has a high density of nicotinic acetylcholine receptors (nAChRs ) (Wada et al,, 1989; Woolf, 1991). We report that strong, brief stimu lation of nAChRs enhanced hippocampal glutamatergic synaptic transmiss ion on two independent time scales and altered the relationship betwee n consecutively evoked synaptic currents. The nicotinic synaptic enhan cement required extracellular calcium and was produced by the activati on of presynaptjc alpha 7-containing nAChRs. Although one form of glut amatergic enhancement lasted only for seconds, another form lasted for minutes after the nicotinic stimulation had ceased and the nicotinic agonist had been washed away. The synaptic enhancement lasting minutes suggests that nAChR activity can initiate calcium-dependent mechanism s that are known to induce glutamatergic synaptic plasticity. The resu lts with evoked synaptic currents showed that nAChR activity can alter the relationship between the incoming presynaptic activity and outgoi ng postsynaptic signaling along glutamatergic fibers. Thus, the same i nformation arriving along the same glutamatergic afferents will be pro cessed differently when properly timed nicotinic activity converges on to the glutamatergic presynaptic terminals. Influencing information pr ocessing at glutamatergic synapses may be one way in which nicotinic c holinergic activity influences cognitive processes. Disruption of thes e nicotinic cholinergic mechanisms may contribute to the deficits asso ciated with the degeneration of cholinergic functions during Alzheimer 's disease.