2. Academic Validation
  3. Behavioral analysis of kainate receptor KO mice and the role of GluK3 subunit in anxiety

Behavioral analysis of kainate receptor KO mice and the role of GluK3 subunit in anxiety

  • Sci Rep. 2024 Feb 24;14(1):4521. doi: 10.1038/s41598-024-55063-z.
Izumi Iida 1 2 3,  Kohtarou Konno 4,  Rie Natsume 5,  Manabu Abe 5,  Masahiko Watanabe 4,  Kenji Sakimura 6,  Miho Terunuma 7
Affiliations

Affiliations

  • 1 Division of Oral Biochemistry, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514, Japan.
  • 2 Research Center for Advanced Oral Science, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514, Japan.
  • 3 Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro, Tokyo, 153-8902, Japan.
  • 4 Department of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo, 060-8638, Japan.
  • 5 Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan.
  • 6 Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, 951-8585, Japan. [email protected].
  • 7 Division of Oral Biochemistry, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514, Japan. [email protected].
PMID: 38402313 DOI: 10.1038/s41598-024-55063-z
Abstract

Kainate receptors (KARs) are one of the ionotropic glutamate receptors in the central nervous system (CNS) comprised of five subunits, GluK1-GluK5. There is a growing interest in the association between KARs and psychiatric disorders, and there have been several studies investigating the behavioral phenotypes of KAR deficient mice, however, the difference in the genetic background has been found to affect phenotype in multiple mouse models of human diseases. Here, we examined GluK1-5 single KO mice in a pure C57BL/6N background and identified that GluK3 KO mice specifically express anxiolytic-like behavior with an alteration in dopamine D2 receptor (D2R)-induced anxiety, and reduced D2R expression in the striatum. Biochemical studies in the mouse cortex confirmed that GluK3 subunits do not assemble with GluK4 and GluK5 subunits, that can be activated by lower concentration of agonists. Overall, we found that GluK3-containing KARs function to express anxiety, which may represent promising anti-anxiety medication targets.

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