1. Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice
- Author
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Daniele Procissi, Yongling Zhu, Herman B. Fernandes, John Marshall, Bryan A. Copits, Geoffrey T. Swanson, Toshihiro Nomura, Jian Xu, Lei Wang, Anis Contractor, and Susumu Mori
- Subjects
0301 basic medicine ,Male ,striatum ,perseverative behavior ,corticostriatal synapse ,Kainate receptor ,Striatum ,Neurotransmission ,Biology ,Medium spiny neuron ,Synaptic Transmission ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Receptors, Kainic Acid ,Cerebellar Diseases ,Biological neural network ,Animals ,Receptor ,lcsh:QH301-705.5 ,Cerebral Cortex ,Mice, Knockout ,Neurons ,Glutamate receptor ,Excitatory Postsynaptic Potentials ,Anatomy ,Corpus Striatum ,030104 developmental biology ,kainate receptor ,nervous system ,lcsh:Biology (General) ,Knockout mouse ,Synapses ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Summary 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.
- Published
- 2017