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

Jian Xu, John J. Marshall, Herman B. Fernandes, Toshihiro Nomura, Bryan A. Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T. Swanson, Anis Contractor

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1848-1857
Number of pages10
JournalCell Reports
Volume18
Issue number8
DOIs
Publication statusPublished - Feb 21 2017

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Keywords

  • corticostriatal synapse
  • kainate receptor
  • perseverative behavior
  • striatum

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Xu, J., Marshall, J. J., Fernandes, H. B., Nomura, T., Copits, B. A., Procissi, D., ... Contractor, A. (2017). Complete Disruption of the Kainate Receptor Gene Family Results in Corticostriatal Dysfunction in Mice. Cell Reports, 18(8), 1848-1857. https://doi.org/10.1016/j.celrep.2017.01.073