Schoettner Konrad, Alonso Mariana, Button Margo, Goldfarb Cassandra, Herrera Juliana, Quteishat Nour, Meyer Christiane, Bergdahl Andreas, Amir Shimon
Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, QC, Canada.
Department of Health, Kinesiology and Applied Physiology, Concordia University, Montreal, QC, Canada.
Front Physiol. 2022 Jun 8;13:922080. doi: 10.3389/fphys.2022.922080. eCollection 2022.
The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of or from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of . Whereas the conditional knockout of and had mild effects on affective behaviors, a pronounced effect on motor functions was found in knockout mice. Subsequent investigation revealed an attenuated response of knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice.
昼夜节律时钟基因在中枢或外周的表达已被证明在行为控制中起着不可或缺的作用。大脑区域特异性时钟基因下调揭示了与神经精神疾病和神经退行性疾病相关的行为表型。然而，时钟基因的具体功能以及导致观察到的表型的潜在机制尚未完全了解。我们评估了纹状体中等棘状神经元（MSN）中条件性敲除或 以及缺失一个拷贝的 的雄性和雌性小鼠的焦虑样和抑郁样行为及运动功能。虽然 和 的条件性敲除对情感行为有轻微影响，但在 敲除小鼠中发现对运动功能有明显影响。随后的研究表明， 敲除小鼠对1型多巴胺受体激动剂治疗的反应减弱，这与MSN中多巴胺信号通路靶点的表达或线粒体呼吸无关。因此，该研究表明 在直接多巴胺信号通路内存在潜在相互作用，这可能为调节小鼠情感行为和运动功能的共同MSN依赖性机制提供联系。
