Nicotinic receptor function: new perspectives from knockout mice

Knockout mice, in which one or more genes of interest are silenced, provide unique opportunities to analyse diverse aspects of gene function in vivo. In particular, the contribution of the encoded protein(s) in complex behavi ours can be assessed. Since the first targeted disruption in 1995 of the ge ne encoding the beta 2-subunit of the nicotinic acetylcholine receptor (nAC hR), all but a few of the mammalian nAChR subunits have been disrupted (i.e , alpha 7, alpha 4, alpha 3, (alpha 9, beta 4 and beta 3). Recent advances brought by genetically modified mice to our understanding of the endogenous composition and role of nAChRs in the nervous system, and of the diverse p harmacological actions of nicotine regarding learning, analgesia, reinforce ment, development and aging in the brain will be discussed.