Ka. Radcliffe et Ja. Dani, NICOTINIC STIMULATION PRODUCES MULTIPLE FORMS OF INCREASED GLUTAMATERGIC SYNAPTIC TRANSMISSION, The Journal of neuroscience, 18(18), 1998, pp. 7075-7083
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.