title: Cortical GluK1 kainate receptors modulate scratching in adult mice.
abstract: Recent investigations into the mechanisms mediating itch transmission have focused on spinal mechanisms, whereas few studies have investigated the role of the cerebral cortex in itch-related behaviors. Human imaging studies show that several cortical regions are active in correspondence with itch, including the anterior cingulate cortex (ACC). We present here evidence of cortical modulation of pruritogen-induced scratching behavior. We combine pharmacological, genetic, and electrophysiological approaches to show that cortical GluK1-containing kainate (KA) receptors are involved in scratching induced by histamine and non-histamine-dependent itching stimuli. We further show that scratching corresponds with enhanced excitatory transmission in the ACC through KA receptor modulation of inhibitory circuitry. In addition, we found that inhibiting GluK1-containing KA receptors in the ACC also reduced behavioral nociceptive responses induced by formalin. Our results reveal a new role of the cortex in pruritogen-induced scratching.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, University of Toronto Center for the Study of Pain, Toronto, Ontario, Canada.
authors.forename: Giannina
authors.initials: G
authors.lastname: Descalzi
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Kohei
authors.initials: K
authors.lastname: Koga
authors.forename: Xiang-Yao
authors.initials: XY
authors.lastname: Li
authors.forename: Kaori
authors.initials: K
authors.lastname: Yamada
authors.forename: Min
authors.initials: M
authors.lastname: Zhuo
mesh_terms: D000818:Animals; D000982:Antipruritics / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D055724:Electrophysiological Phenomena; D016762:Genes, fos / Q000235:genetics / Q000502:physiology; D006632:Histamine / Q000494:pharmacology / Q000502:physiology; D007150:Immunohistochemistry; D007249:Inflammation / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008845:Microinjections; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011537:Pruritus / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D000982:Antipruritics; D006632:Histamine; D018092:Kainic Acid Receptors; D005680:gamma-Aminobutyric Acid
keywords: cortex; glutamatergic transmission; inhibitory transmission; itch; kainate receptors; scratching