NICOTINE ENHANCEMENT OF FAST EXCITATORY SYNAPTIC TRANSMISSION IN CNS BY PRESYNAPTIC RECEPTORS

The behavioral and cognitive effects of nicotine suggest that nicotini c acetylcholine receptors (nAChRs) participate in central nervous syst em (CNS) function. Although nAChR subunit messenger RNA (mRNA) and nic otine binding sites are common in the brain, there is little evidence for synapses mediated by nAChRs in the CNS. To test whether CNS nAChRs might modify rather than mediate transmission, the regulation of exci tatory synaptic transmission by these receptors was examined. Nanomola r concentrations of nicotine enhanced both glutamatergic and cholinerg ic synaptic transmission by activation of presynaptic nAChRs that incr eased presynaptic [Ca2+](i). Pharmacological and subunit deletion expe riments reveal that these presynaptic nAChRs include the alpha 7 subun it. These findings reveal that CNS nAChRs enhance fast excitatory tran smission, providing a likely mechanism for the complex behavioral effe cts of nicotine.