Data from: Caspr3-deficient mice exhibit low motor learning during the early phase of the accelerated rotarod task

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.

Caspr3（接触蛋白关联蛋白样3，Contactin-associated protein-like 3，简称Cntnap3）是隶属于Caspr家族的神经细胞黏附分子。我们此前的研究证实，Caspr3在小鼠出生后第1至第2周于基底神经节中广泛表达，具体涵盖纹状体、苍白球外侧部、丘脑底核及黑质。然而，其生理功能目前仍不甚明确。本研究针对Caspr3敲除（KO）小鼠与同背景野生型（WT）小鼠开展了一系列行为学分析，以探究Caspr3在脑功能中的作用。结果显示，多数行为学指标在Caspr3-KO与WT小鼠间无显著差异，但我们发现Caspr3-KO小鼠在加速旋转棒实验的早期阶段表现不佳——该任务的检测指标为小鼠在转速递增的旋转棒上的坠落潜伏期。在实验晚期阶段，Caspr3-KO小鼠的表现可追及WT小鼠，这提示Caspr3的缺失会导致运动学习能力出现延迟。随后，我们通过使用靶向神经元活动间接标志物c-Fos的抗体开展免疫组织化学实验，检测了加速旋转棒训练后的神经活动变化。研究发现，加速旋转棒训练可使Caspr3-KO与WT小鼠的背侧纹状体、小脑及运动皮层内的c-Fos阳性细胞数量均出现升高，但Caspr3-KO小鼠背侧纹状体中的c-Fos阳性细胞数量显著低于WT小鼠。而两组小鼠腹侧纹状体中的c-Fos表达水平均未因训练发生改变。综上，我们的研究结果表明，Caspr3-KO小鼠背侧纹状体的神经细胞激活水平降低，会导致其在加速旋转棒任务中的运动学习能力下降。