Functional distribution and regulation of neuronal nicotinic ACh receptors in the mammalian brain

Abstract

The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability throughout the nervous system by acting on the cys-loop cationconducting ligand-gated nicotinic ACh receptor channels (nAChRs). These receptors are widely distributed throughout the nervous system, being expressed on neurons and nonneuronal cells where they participate in a variety of physiological responses. In the mammalian brain, nine different subunits have been discovered thus far, which assemble into pentameric complexes with much diversity. The neuronal subtypes of these receptors, primarily composed of the α7 and non-α7 subtypes (e.g. a4ß2 and a3ß4), are involved in a variety of neurobehavioral processes such as anxiety, the central processing of pain, food intake, nicotine-seeking behavior, and cognitive functions. Neuronal nAChR dysfunction is involved in the pathophysiology of many neurological disorders and diseases including (but not limited to) Alzheimer's and Parkinson's diseases, schizophrenia, and epilepsy. Here I will briefly discuss the functional makeup and expression of nAChRs in the mammalian brain, and the role that they play in these various circuits, in normal function, and in disease.