Physiological roles of CNS muscarinic receptors gained from knockout mice. (1st July 2018)

• Record Type: Journal Article
• Authors: Thomsen, Morgane; Sørensen, Gunnar; Dencker, Ditte
• Is Part Of: Neuropharmacology. Volume 136:Part C(2018)
• Page Start: 411
• Page End: 420
• Publication Date: 2018-07-01
• Subjects: Cholinergic -- Muscarinic -- Mice -- Knockout -- Knock-out -- Null mutation; CIN cholinergic interneuron -- CAMKIIα Ca2+/calmodulin-dependent protein kinase IIα -- EPSP excitatory postsynaptic potentials -- HPA hypothalamic-pituitary-adrenocortical -- MAPK mitogen-activated protein kinase -- LTD long-term depression -- LTP long-term potentiation -- MSN medium spiny neurons -- mAChR muscarinic acetylcholine receptor -- PAM positive allosteric modulator -- PI phosphatidyl inositol -- PPI prepulse inhibition -- SNc substantia nigra pars compacta -- VTA ventral tegmental area; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2017.09.011
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Because the five muscarinic acetylcholine receptor subtypes have overlapping distributions in many CNS tissues, and because ligands with a high degree of selectivity for a given subtype long remained elusive, it has been difficult to determine the physiological functions of each receptor. Genetically engineered knockout mice, in which one or more muscarinic acetylcholine receptor subtype has been inactivated, have been instrumental in identifying muscarinic receptor functions in the CNS, at the neuronal, circuit, and behavioral level. These studies revealed important functions of muscarinic receptors modulating neuronal activity and neurotransmitter release in many brain regions, shaping neuronal plasticity, and affecting functions ranging from motor and sensory function to cognitive processes. As gene targeting technology evolves including the use of conditional, cell type specific strains, knockout mice are likely to continue to provide valuable insights into brain physiology and pathophysiology, and advance the development of new medications for a range of conditions such as Alzheimer's disease, Parkinson's disease, schizophrenia, and addictions, as well as non-opioid analgesics. This article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'.