Imperial College London

Prof. William Wisden F. Med. Sci.

Faculty of Natural SciencesDepartment of Life Sciences

Chair in Molecular Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 9744w.wisden Website CV

 
 
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Location

 

401BSir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Brickley:10.1016/j.cophys.2017.12.011,
author = {Brickley, SG and Wisden, W and Franks, NP},
doi = {10.1016/j.cophys.2017.12.011},
journal = {Current Opinion in Physiology},
pages = {51--57},
title = {Modulation of GABA-A receptor function and sleep},
url = {http://dx.doi.org/10.1016/j.cophys.2017.12.011},
volume = {2},
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The intravenous general anaesthetics (propofol & etomidate), the barbiturates, steroids (e.g. alphaxalone, allopregnanalone), the benzodiazepines and the widely prescribed ‘sleeping pill’, the imidazopyridine zolpidem, are all positive allosteric modulators (PAMs) of GABAA receptors. PAMs enhance ongoing GABAergic communication between neurons. For treating primary insomnia, zolpidem remains a gold-standard medication — it reduces the latency to NREM sleep with a rapid onset and short half-life, leading to relatively few hangover effects. In this review, we discuss the role of the different GABAA receptor subtypes in the action of sleep-promoting drugs. Certain neuronal hub areas exert disproportionate effects on the brain's vigilance states. For example, injecting GABAA agonists and PAMs into the mesopontine tegmental anaesthesia area (MPTA) induces an anaesthetic-like state. Similarly, by selectively increasing the GABA drive onto arousal-promoting nuclei, such as the histaminergic neurons in the tuberomammillary nucleus, a more natural NREM-like sleep emerges. Some patients suffering from idiopathic hypersomnia have an unidentified GABAA receptor PAM in their cerebral spinal fluid. Treating these patients with benzodiazepine PAM site antagonists improves their symptoms. More knowledge of endogenous GABAA receptor PAMs could provide insight into sleep physiology.
AU - Brickley,SG
AU - Wisden,W
AU - Franks,NP
DO - 10.1016/j.cophys.2017.12.011
EP - 57
SN - 2468-8673
SP - 51
TI - Modulation of GABA-A receptor function and sleep
T2 - Current Opinion in Physiology
UR - http://dx.doi.org/10.1016/j.cophys.2017.12.011
UR - http://hdl.handle.net/10044/1/55616
VL - 2
ER -