Physiological roles of CNS muscarinic receptors gained from knockout mice

TY - JOUR

T1 - Physiological roles of CNS muscarinic receptors gained from knockout mice

AU - Thomsen, Morgane

AU - Sørensen, Gunnar

AU - Dencker, Ditte

PY - 2018/7/1

Y1 - 2018/7/1

N2 - 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’.

AB - 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’.

KW - Cholinergic

KW - Knock-out

KW - Knockout

KW - Mice

KW - Muscarinic

KW - Null mutation

U2 - 10.1016/j.neuropharm.2017.09.011

DO - 10.1016/j.neuropharm.2017.09.011

M3 - Review

C2 - 28911965

AN - SCOPUS:85029433837

SN - 0028-3908

VL - 136

SP - 411

EP - 420

JO - Neuropharmacology

JF - Neuropharmacology

IS - Part C

ER -