Imperial College London
Alternate

ProfessorStephenBrickley

Faculty of Natural Sciences, Department of Life Sciences

Professor of Systems Neuroscience
 
 
 
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Contact

 

+44 (0)20 7594 7699s.brickley

 
 
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Location

 

402ASir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wisden:2016:10.1523/JNEUROSCI.3714-15.2016,
author = {Wisden, W and Uygun, DS and Ye, Z and Zecharia, AY and Harding, EC and Yu, X and Yustos, R and Vyssotski, AL and Brickley, SG and Franks, NP},
doi = {10.1523/JNEUROSCI.3714-15.2016},
journal = {Journal of Neuroscience},
pages = {11171--11184},
title = {Bottom-Up versus Top-Down Induction of Sleep by Zolpidem Acting on Histaminergic and Neocortex Neurons},
url = {http://dx.doi.org/10.1523/JNEUROSCI.3714-15.2016},
volume = {36},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase sleep time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases the EEG power, an effect that depends on α1 subunit-containing receptors, and which may make zolpidem-induced sleep less optimal. In this paper, we investigate whether zolpidem needs to potentiate only particular GABAergic pathways to induce sleep without reducing EEG power. Mice with a knock-in F77I mutation in the GABAA receptor γ2 subunit gene are zolpidem-insensitive. Using these mice, GABAA receptors in the frontal motor neocortex and hypothalamic (tuberomammillary nucleus) histaminergic-neurons of γ2I77 mice were made selectively sensitive to zolpidem by genetically swapping the γ2I77 subunits with γ2F77 subunits. When histamine neurons were made selectively zolpidem-sensitive, systemic administration of zolpidem shortened sleep latency and increased sleep time. But in contrast to the effect of zolpidem on wild-type mice, the power in the EEG spectra of NREM sleep was not decreased, suggesting that these EEG power-reducing effects of zolpidem do not depend on reduced histamine release. Selective potentiation of GABAA receptors in the frontal cortex by systemic zolpidem administration also reduced sleep latency, but less so than for histamine neurons. These results could help with the design of new sedatives that induce a more natural sleep.
AU  - Wisden,W
AU  - Uygun,DS
AU  - Ye,Z
AU  - Zecharia,AY
AU  - Harding,EC
AU  - Yu,X
AU  - Yustos,R
AU  - Vyssotski,AL
AU  - Brickley,SG
AU  - Franks,NP
DO  - 10.1523/JNEUROSCI.3714-15.2016
EP  - 11184
PY  - 2016///
SN  - 0270-6474
SP  - 11171
TI  - Bottom-Up versus Top-Down Induction of Sleep by Zolpidem Acting on Histaminergic and Neocortex Neurons
T2  - Journal of Neuroscience
UR  - http://dx.doi.org/10.1523/JNEUROSCI.3714-15.2016
UR  - http://hdl.handle.net/10044/1/39100
VL  - 36
ER  -
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