Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice

• Published in: Cell reports (Cambridge) 2017-02, Vol.18 (8), p.1848-1857
• Main Authors: Xu, Jian, Marshall, John J., Fernandes, Herman B., Nomura, Toshihiro, Copits, Bryan A., Procissi, Daniele, Mori, Susumu, Wang, Lei, Zhu, Yongling, Swanson, Geoffrey T., Contractor, Anis
• Format: Article
• Language: English
• Subjects: Animals; Cerebellar Diseases - genetics; Cerebellar Diseases - metabolism; Cerebral Cortex - metabolism; Corpus Striatum - metabolism; corticostriatal synapse; Excitatory Postsynaptic Potentials - genetics; Excitatory Postsynaptic Potentials - physiology; kainate receptor; Male; Mice; Mice, Knockout; Neurons - metabolism; perseverative behavior; Receptors, Kainic Acid - genetics; Receptors, Kainic Acid - metabolism; striatum; Synapses - metabolism; Synaptic Transmission - genetics; Synaptic Transmission - physiology
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2017.01.073

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. [Display omitted] •Mice with loss of all five kainate receptor genes have striatal-dependent phenotypes•Mutant mice display perseverative and compulsive behavior and locomotor deficits•Synapses onto striatal neurons have morphological and functional deficits Xu et al. generated mice with all members of the kainate receptor family of glutamate receptors deleted. These mice demonstrate compulsive and perseverative behaviors and deficits in the function and number of excitatory synapses in the striatum. This demonstrates that kainate receptors regulate the proper formation and function of striatal circuits.