α7 Nicotinic acetylcholine receptors and their role in cognition

The precise role of nicotinic acetylcholine receptors (nAChRs) in central cognitive processes still remains incompletely understood almost 150 years after its initial discovery. Central nAChRs are activated by acetylcholine, which functions in the extracellular space as a nonsynaptic messenger. Recently, a novel concept in the nAChR mode of operation has been described as a fast-type nonsynaptic transmission. In this review, we attempt to summarise the experimental findings that support the role of one of the most distributed receptor subtypes, the alpha 7 nAChRs, and particularly focus on its procognitive effects following receptor activation. The basic characteristics of alpha 7 nAChRs are discussed, from receptor homology to cellular-level functions. Synaptic plasticity is often implicated with alpha 7 nAChRs on the basis of several diverse studies. Here, we provide a summary of the plastic features of the alpha 7 receptor subtype and its role in higher level cognitive function. Finally, recent clinical evidence is reviewed, which demonstrates with increasing confidence the promise alpha 7 nAChRs as a molecular target in future pharmacotherapy to prevent cognitive decline in various types of dementia, specifically, via the development of positive allosteric modulator compounds. (C) 2012 Elsevier Inc. All rights reserved.