title: Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice.
abstract: Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits. There were deficits in corticostriatal input to spiny projection neurons (SPNs) in the dorsal striatum and correlated reductions in spine density. The behavioral alterations were not present in mice only lacking the primary receptor subunit expressed in adult striatum (GluK2 KO), suggesting that signaling through multiple receptor types is required for proper striatal function. This demonstrates that alterations in striatal function dominate the behavioral phenotype in mice without kainate receptors.
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Marshall
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Herman B
authors.initials: HB
authors.lastname: Fernandes
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Copits
authors.affiliation: Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Procissi
authors.affiliation: Department of Radiology, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Susumu
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Yongling
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Swanson
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Department of Neurobiology, Weinberg College of Arts and Sciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: a-contractor@northwestern.edu.
authors.forename: Anis
authors.initials: A
authors.lastname: Contractor
mesh_terms: D000818:Animals; D002526:Cerebellar Diseases / Q000235:genetics* / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000235:genetics* / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
chemical_list: D018092:Kainic Acid Receptors
keywords: corticostriatal synapse; kainate receptor; perseverative behavior; striatum