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 α7 nAChRs, and particularly focus on its procognitive effects following receptor activation. The basic characteristics of α7 nAChRs are discussed, from receptor homology to cellular-level functions. Synaptic plasticity is often implicated with α7 nAChRs on the basis of several diverse studies. Here, we provide a summary of the plastic features of the α7 receptor subtype and its role in higher level cognitive function. Finally, recent clinical evidence is reviewed, which demonstrates with increasing confidence the promise α7 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.

► Nonsynaptic ACh can activate high-affinity α7 nAChRs offering an ideal drug target. ► α7 positive allosteric modulator molecules can boost activation of α7 nAChRs. ► Activation of α7 nAChRs prolongs adaptive responses providing cellular memory. ► Plasticity and cognitive studies support the procognitive role of α7. ► Targeting α7 nAChRs is a current trend for cognitive enhancement in dementia.