HIPPOCAMPAL SYNAPTIC TRANSMISSION ENHANCED BY LOW CONCENTRATIONS OF NICOTINE

NICOTINE obtained from tobacco can improve learning and memory on vari ous tasks and has been linked to arousal, attention, rapid information processing, working memory, and longterm memories that can cause crav ing years after someone has stopped smoking(1,2). One likely target fo r these effects is the hippocampus, a centre for learning and memory t hat has rich cholinergic innervation and dense nicotinic acetylcholine receptor (nAChR) expression(3-6). During Alzheimer's dementia there a re fewer nAChRs and the cholinergic inputs to the hippocampus degenera te(7). However, there is no evidence for fast synaptic transmission me diated by nAChRs in the hippocampus, and their role is not understood( 8,9). Nicotine is known to act on presynaptic nAChRs within the habenu la of chick to enhance glutamatergic transmission(10); here we report that a similar mechanism operates in the hippocampus. Measurements of intracellular Ca2+ in single mossy-fibre presynaptic terminals indicat e that nAChRs containing the alpha 7 subunit can mediate a Ca2+ influx that is sufficient to induce vesicular neurotransmitter release. We p ropose that nicotine from tobacco influences cognition by enhancing sy naptic transmission. Conversely, a decreased efficacy of transmission may account for the deficits associated with the loss of cholinergic i nnervation during Alzheimer's disease.