Cortical GluK1 kainate receptors modulate scratching in adult mice
Article first published online: 19 JUL 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 126, Issue 5, pages 636–650, September 2013
How to Cite
J. Neurochem. (2013) 126, 636–650.
- Issue published online: 23 AUG 2013
- Article first published online: 19 JUL 2013
- Accepted manuscript online: 21 JUN 2013 03:49AM EST
- Manuscript Accepted: 12 JUN 2013
- Manuscript Revised: 5 JUN 2013
- Manuscript Received: 25 FEB 2013
- Fragile-X research foundation of Canada
- E. Fidlar Ontario Graduate Scholarship
- glutamatergic transmission;
- inhibitory transmission;
- kainate receptors;
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.
Cortical contribution to pruritogen-induced scratching is shown in an animal model. Through a combination of pharmacological, genetic, and electrophysiological data, we show that cortical GluK1-containing kainate receptors (KAR) are involved in pruritogen-induced scratching. Peripheral application of itching stimuli activates excitatory afferents projecting to ACC layer II/III pyramidal neurons, initiating presynaptic glutamate (Glu) release which activates postsynaptic AMPA receptors. Simultaneously, presynaptic Glu activates presynaptic KAR located on inhibitory neurons, thereby modulating evoked GABA release and affecting the attenuation of the postsynaptic response.