Nicotinic receptors in the brain - Molecular biology, function, and therapeutics

Although the psychological and physiological effects of nicotine have long suggested that nicotine exerts specific actions in the brain, the identification of neuronal nicotinic receptors (nAChRs) only began in the past few years with the development of molecular genetics. It is now clear that neuronal nAChRs form a family of highly heterogenous receptor subtypes, as evidenced by the number of genes encoding nAChR subunits, the diversity of immunopurified receptor proteins, and the multiple functional types of ligand-gated ion channels. Neuronal nAChRs have discrete localizations within the brain, and are involved in modulating neuronal firing and transmitter release. Cumulative evidence from animal and human studies indicates that nicotinic systems play a major role in higher cognitive functions and dysfunctions. In particular, the loss of cortical nAChRs is a neurochemical hallmark of Alzheimer (AD) and Parkinson (PD) diseases. In addition, nicotine improves memory and attention in AD and PD. Our recent studies using electrophysiological biochemical and behavioral approaches suggest that the prefrontal cortex is a major target site for the cognitive actions of nicotine.