Département de Neurobiologie des Rythmes, Centre National de la Recherche Scientifique, Unité Propre de Recherche 3212 associée à l'Université de Strasbourg, Institut Fédératif des Neurosciences de Strasbourg, 67084 Strasbourg, France.
J Neurosci. 2010 Feb 3;30(5):1894-904. doi: 10.1523/JNEUROSCI.5855-09.2010.
The cerebellum participates in motor coordination as well as in numerous cerebral processes, including temporal discrimination. Animals can predict daily timing of food availability, as manifested by food-anticipatory activity under restricted feeding. By studying ex vivo clock gene expression by in situ hybridization and recording in vitro Per1-luciferase bioluminescence, we report that the cerebellum contains a circadian oscillator sensitive to feeding cues (i.e., whose clock gene oscillations are shifted in response to restricted feeding). Food-anticipatory activity was markedly reduced in mice injected intracerebroventricularly with an immunotoxin that depletes Purkinje cells (i.e., OX7-saporin). Mice bearing the hotfoot mutation (i.e., Grid2(ho/ho)) have impaired cerebellar circuitry and mild ataxic phenotype. Grid2(ho/ho) mice fed ad libitum showed regular behavioral rhythms and day-night variations of clock gene expression in the hypothalamus and cerebellum. When challenged with restricted feeding, however, Grid2(ho/ho) mice did not show any food-anticipatory rhythms, nor timed feeding-induced changes in cerebellar clock gene expression. In hypothalamic arcuate and dorsomedial nuclei, however, shifts in Per1 expression in response to restricted feeding were similar in cerebellar mutant and wild-type mice. Furthermore, plasma corticosterone and metabolites before mealtime did not differ between cerebellar mutant and wild-type mice. Together, these data define a role for the cerebellum in the circadian timing network and indicate that the cerebellar oscillator is required for anticipation of mealtime.
小脑参与运动协调以及许多大脑过程，包括时间辨别。动物可以预测食物供应的日常时间，表现为在限制进食下的食物预期活动。通过研究原位杂交的离体时钟基因表达和体外 Per1-荧光素酶生物发光记录，我们报告小脑包含对进食线索敏感的生物钟振荡器（即，其时钟基因振荡响应限制进食而改变）。用免疫毒素脑室注射（即 OX7-细胞松弛素）耗尽浦肯野细胞的小鼠，其食物预期活动明显减少。Grid2（ho/ho）突变小鼠（即 Grid2（ho/ho））具有受损的小脑电路和轻微的共济失调表型。自由进食的 Grid2（ho/ho）小鼠表现出规律的行为节律和下丘脑和小脑时钟基因表达的昼夜变化。然而，当受到限制进食的挑战时，Grid2（ho/ho）小鼠没有表现出任何食物预期节律，也没有定时进食诱导的小脑时钟基因表达变化。然而，在下丘脑弓状核和背内侧核中，限制进食对 Per1 表达的改变在小脑突变体和野生型小鼠中相似。此外，餐前的血浆皮质酮和代谢物在小脑突变体和野生型小鼠之间没有差异。总之，这些数据定义了小脑在生物钟计时网络中的作用，并表明小脑振荡器是预测进餐时间所必需的。
