Wakefulness Is Governed by GABA and Histamine Cotransmission

• DOI: 10.1016/j.neuron.2015.06.003
• Publication Date: 2015-06-18T17:13:51Z
• Authors: Xiao Yu; Zhiwen Ye; Catriona M. Houston; Anna Y. Zecharia; Ying Ma; Zhe Zhang; David S. Uygun; Susan Parker; Alexei L. Vyssotski; Raquel Yustos; Nicholas P. Franks; Stephen G. Brickley; William Wisden
• Keywords: Neurons; 0303 health sciences; Vesicular Inhibitory Amino Acid Transport Proteins; Neuroscience(all); Pyramidal Cells; 2800 General Neuroscience; Neocortex; Neural Inhibition; Receptors, GABA-A; Synaptic Transmission; Article; Axons; Neostriatum; Optogenetics; Mice; 03 medical and health sciences; Gene Knockdown Techniques; Hypothalamic Area, Lateral; 570 Life sciences; biology; Animals; Wakefulness; gamma-Aminobutyric Acid; 10194 Institute of Neuroinformatics; Histamine

Histaminergic neurons in the tuberomammilary nucleus (TMN) of hypothalamus form a widely projecting, wake-active network that sustains arousal. Yet most histaminergic contain GABA. Selective siRNA knockdown vesicular GABA transporter (vgat, SLC32A1) produced hyperactive mice with an exceptional amount sustained wakefulness. Ablation vgat gene throughout TMN further sharpened this phenotype. Optogenetic stimulation caudate-putamen and neocortex "histaminergic" axonal projections from evoked tonic (extrasynaptic) GABAA receptor Cl− currents onto medium spiny pyramidal neurons. These were abolished following removal area. Thus generate paracrine GABAergic signal serves to provide brake on overactivation histamine, but could also increase precision neocortical processing. The long range histamine-GABA suggests extrasynaptic inhibition will be coordinated over large striatal areas.