Department of Neuroscience, Erasmus Medical Centre, 3015 GE Rotterdam, The Netherlands.
J Neurosci. 2013 Jul 31;33(31):12599-618. doi: 10.1523/JNEUROSCI.1642-13.2013.
In addition to its well established role in motor coordination, the cerebellum has been hypothesized to be involved in the control of cognitive and emotional functions. Although a cerebellar contribution to nonmotor functions has been supported by recent studies in human and monkey, it remains to be clarified with an in-depth, systematic approach in mouse mutants. Here we subjected four different cerebellar cell-specific mouse lines whereby the excitatory or inhibitory input to Purkinje cells (PCs) and/or PC postsynaptic plasticity were compromised, to a wide battery of standard cognitive and emotional tests. The four lines, which have all been shown to suffer from impaired motor learning without being ataxic, were tested for social behavior using a sociability task, for spatial navigation using the Morris watermaze, for fear responses using contextual and cued conditioning, and general anxiety using the open-field task. None of the four cerebellum-specific genetic perturbations showed significantly impaired cognitive or emotional behavior. In fact, even without correction for multiple comparisons, only 5 of 154 statistical comparisons showed a marginally significant deficit. Therefore, our data indicate that none of the perturbations of cerebellar functioning studied here affected the cognitive or emotional tests we used. This suggests that there may be a differential impact of the murine and human cerebellum on nonmotor functions. We hypothesize that these differences could be a consequence of the remarkable enlargement of the cerebellar hemispheres during the latest phase of vertebrate phylogeny, which occurred in parallel with the evolution of the cerebral cortex.
除了在运动协调方面的成熟作用外,小脑还被假设参与控制认知和情绪功能。尽管最近的人类和猴子研究支持小脑对非运动功能的贡献,但在小鼠突变体中仍需要通过深入、系统的方法来阐明。在这里,我们对四种不同的小脑细胞特异性小鼠品系进行了研究,这些品系中浦肯野细胞(PCs)的兴奋性或抑制性输入和/或 PC 突触后可塑性受到了损害,然后对它们进行了广泛的标准认知和情绪测试。这四种品系都表现出运动学习障碍,但没有共济失调,我们使用社交任务测试它们的社交行为,使用 Morris 水迷宫测试它们的空间导航能力,使用情境和线索条件测试它们的恐惧反应,使用开阔场地任务测试它们的一般焦虑。四种小脑特异性遗传扰动中没有一种表现出明显的认知或情绪行为障碍。事实上,即使不进行多次比较的校正,在 154 次统计比较中,只有 5 次显示出边缘显著的缺陷。因此,我们的数据表明,我们研究的小脑功能的这些扰动都没有影响我们使用的认知或情绪测试。这表明,小脑对非运动功能的影响可能存在差异。我们假设,这些差异可能是脊椎动物进化过程中最后阶段小脑半球显著增大的结果,这与大脑皮层的进化同时发生。