Characterization of Affective Behaviors and Motor Functions in Mice With a Striatal-Specific Deletion of and .

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.