Caspr3 (Contactin-associated protein-like 3, Cntnap3) is a neural cell adhesion molecule belonging to the Caspr family. We have recently shown that Caspr3 is expressed abundantly between the first and second postnatal weeks in the mouse basal ganglia, including the striatum, external segment of the globus pallidus, subthalamic nucleus, and substantia nigra. However, its physiological role remains largely unknown. In this study, we conducted a series of behavioral analyses on Capsr3-knockout (KO) mice and equivalent wild-type (WT) mice to investigate the role of Caspr3 in brain function. No significant differences were observed in most behavioral traits between Caspr3-KO and WT mice, but we found that Caspr3-KO mice performed poorly during the early phase of the accelerated rotarod task in which latency to falling off a rod rotating with increasing velocity was examined. In the late phase, the performance of the Caspr3-KO mice caught up to the level of WT mice, suggesting that the deletion of Caspr3 caused a delay in motor learning. We then examined changes in neural activity after training on the accelerated rotarod by conducting immunohistochemistry using antibody to c-Fos, an indirect marker for neuronal activity. Experience of the accelerated rotarod task caused increases in the number of c-Fos-positive cells in the dorsal striatum, cerebellum, and motor cortex in both Caspr3-KO and WT mice, but the number of c-Fos-positive cells was significantly lower in the dorsal striatum of Caspr3-KO mice than in that of WT mice. The expression of c-Fos in the ventral striatum of Caspr3-KO and WT mice was not altered by the training. Our findings suggest that reduced activation of neural cells in the dorsal striatum in Caspr3-KO mice leads to a decline in motor learning in the accelerated rotarod task.

Image files for c-Fos immunohistochemistryAll the image files (Tiff) used in this paper as well as an excel file in which a list of names and short descriptions of the image files are indicated will be found in this folder.c-Fos　image.zip