Imperial College London

Prof. William Wisden F. Med. Sci.

Faculty of Natural SciencesDepartment of Life Sciences

Chair in Molecular Neuroscience



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




401BSir Ernst Chain BuildingSouth Kensington Campus






BibTex format

author = {Yu, X and Zhiwen, Y and Houston, CM and Zecharia, AY and Ma, Y and Zhang, Z and Uygun, DS and Parker, S and Vyssotski, AL and Yustos, Y and Franks, NP and Brickley, SG and Wisden, W},
doi = {10.1016/j.neuron.2015.06.003},
journal = {Neuron},
pages = {164--178},
title = {Wakefulness is governed by GABA and histamine co-transmission},
url = {},
volume = {87},
year = {2015}

RIS format (EndNote, RefMan)

AB - Histaminergic neurons in the tuberomammilary nucleus (TMN) of the hypothalamus form a widely projecting, wake-active network that sustains arousal. Yet most histaminergic neurons contain GABA. Selective siRNA knockdown of the vesicular GABA transporter (vgat, SLC32A1) in histaminergic neurons produced hyperactive mice with an exceptional amount of sustained wakefulness. Ablation of the vgat gene throughout the TMN further sharpened this phenotype. Optogenetic stimulation in the caudate-putamen and neocortex of “histaminergic” axonal projections from the TMN evoked tonic (extrasynaptic) GABAA receptor Cl− currents onto medium spiny neurons and pyramidal neurons. These currents were abolished following vgat gene removal from the TMN area. Thus wake-active histaminergic neurons generate a paracrine GABAergic signal that serves to provide a brake on overactivation from histamine, but could also increase the precision of neocortical processing. The long range of histamine-GABA axonal projections suggests that extrasynaptic inhibition will be coordinated over large neocortical and striatal areas.
AU - Yu,X
AU - Zhiwen,Y
AU - Houston,CM
AU - Zecharia,AY
AU - Ma,Y
AU - Zhang,Z
AU - Uygun,DS
AU - Parker,S
AU - Vyssotski,AL
AU - Yustos,Y
AU - Franks,NP
AU - Brickley,SG
AU - Wisden,W
DO - 10.1016/j.neuron.2015.06.003
EP - 178
PY - 2015///
SN - 0896-6273
SP - 164
TI - Wakefulness is governed by GABA and histamine co-transmission
T2 - Neuron
UR -
UR -
VL - 87
ER -