Article

Cholinergic receptors: functional role of nicotinic ACh receptors in brain circuits and disease.

Laboratory of Neurobiology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, P.O. Box 12233, Mail Drop F2-08, Research Triangle Park, NC, 27709, USA, .
Pflügers Archiv - European Journal of Physiology (Impact Factor: 3.07). 01/2013; DOI: 10.1007/s00424-012-1200-1
Source: PubMed

ABSTRACT The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability throughout the nervous system by acting on both the cys-loop ligand-gated nicotinic ACh receptor channels (nAChRs) and the G protein-coupled muscarinic ACh receptors (mAChRs). The hippocampus is an important area in the brain for learning and memory, where both nAChRs and mAChRs are expressed. The primary cholinergic input to the hippocampus arises from the medial septum and diagonal band of Broca, the activation of which can activate both nAChRs and mAChRs in the hippocampus and regulate synaptic communication and induce oscillations that are thought to be important for cognitive function. Dysfunction in the hippocampal cholinergic system has been linked with cognitive deficits and a variety of neurological disorders and diseases, including Alzheimer's disease and schizophrenia. My lab has focused on the role of the nAChRs in regulating hippocampal function, from understanding the expression and functional properties of the various subtypes of nAChRs, and what role these receptors may be playing in regulating synaptic plasticity. Here, I will briefly review this work, and where we are going in our attempts to further understand the role of these receptors in learning and memory, as well as in disease and neuroprotection.

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    ABSTRACT: The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability by acting on the cys-loop cation-conducting ligand-gated nicotinic ACh receptor (nAChR) channels. These receptors are widely distributed throughout the central nervous system (CNS), being expressed on neurons and non-neuronal cells, where they participate in a variety of physiological responses such as anxiety, the central processing of pain, food intake, nicotine seeking behavior, and cognitive functions. In the mammalian brain, nine different subunits have been found thus far, which assemble into pentameric complexes with much subunit diversity; however, the α7 and α4β2 subtypes predominate in the CNS. Neuronal nAChR dysfunction is involved in the pathophysiology of many neurological disorders. Here we will briefly discuss the functional makeup and expression of the nAChRs in mammalian brain, and their role as targets in neurodegenerative diseases (in particular Alzheimer's disease, AD), neurodevelopmental disorders (in particular autism and schizophrenia), and neuropathic pain. Published by Elsevier Ltd.
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