Division of Oral Biochemistry, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan; Research Center for Advanced Oral Science, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8514, Japan.
Department of Anatomy, Faculty of Medicine, Hokkaido University, Sapporo 060-8638, Japan.
Behav Brain Res. 2021 May 7;405:113194. doi: 10.1016/j.bbr.2021.113194. Epub 2021 Feb 22.
Kainate receptors (KARs) are members of the glutamate receptor family that regulate synaptic function in the brain. Although they are known to be associated with psychiatric disorders, how they are involved in these disorders remains unclear. KARs are tetrameric channels assembled from a combination of GluK1-5 subunits. Among these, GluK2 and GluK5 subunits are the major heteromeric subunits in the brain. To determine the functional similarities and differences between GluK2 and GluK5 subunits, we generated GluK2 KO and GluK5 KO mice on a C57BL/6N background, a well-characterized inbred strain, and compared their behavioral phenotypes. We found that GluK2 KO and GluK5 KO mice exhibited the same phenotypes in many tests, such as reduced locomotor activity, impaired motor function, and enhanced depressive-like behavior. No change was observed in motor learning, anxiety-like behavior, or sociability. Additionally, we identified subunit-specific phenotypes, such as reduced motivation toward their environment in GluK2 KO mice and an enhancement in the contextual memory in GluK5 KO mice. These results revealed that GluK2 and GluK5 subunits not only function in a coordinated manner but also have a subunit-specific role in regulating behavior. To summarize, we demonstrated subunit-specific and common behavioral effects of GluK2 and GluK5 subunits for the first time. Moreover, to the best of our knowledge, this is the first evidence of the involvement of the GluK5 subunit in the expression of depressive-like behavior and contextual memory, which strongly indicates its role in psychiatric disorders.
kainate 受体 (KAR) 是谷氨酸受体家族的成员，可调节大脑中的突触功能。虽然已知它们与精神疾病有关，但它们如何参与这些疾病尚不清楚。KAR 是由 GluK1-5 亚基组合形成的四聚体通道。在这些亚基中，GluK2 和 GluK5 亚基是大脑中的主要异源二聚体亚基。为了确定 GluK2 和 GluK5 亚基之间的功能相似性和差异性，我们在 C57BL/6N 背景下生成了 GluK2 KO 和 GluK5 KO 小鼠，这是一种经过充分表征的近交系，并比较了它们的行为表型。我们发现 GluK2 KO 和 GluK5 KO 小鼠在许多测试中表现出相同的表型，例如运动活性降低、运动功能受损和抑郁样行为增强。在运动学习、焦虑样行为或社交性方面没有观察到变化。此外，我们还确定了亚基特异性表型，例如 GluK2 KO 小鼠对环境的动机降低，以及 GluK5 KO 小鼠的情景记忆增强。这些结果表明，GluK2 和 GluK5 亚基不仅协同发挥作用，而且在调节行为方面具有亚基特异性作用。总之，我们首次证明了 GluK2 和 GluK5 亚基具有亚基特异性和共同的行为效应。此外，据我们所知，这是首次证明 GluK5 亚基参与表达抑郁样行为和情景记忆的证据，这强烈表明其在精神疾病中的作用。
