Neurophysiology of Brain Circuits Team, Institut de Biologie de l'Ecole Normale Supérieure (IBENS), Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, Paris, France.
Cereb Cortex. 2019 Apr 1;29(4):1752-1766. doi: 10.1093/cercor/bhy346.
In Parkinson's disease, the degeneration of the midbrain dopaminergic neurons is consistently associated with modified metabolic activity in the cerebellum. Here we examined the functional reorganization taking place in the cerebello-cerebral circuit in a murine model of Parkinson's disease with 6-OHDA lesion of midbrain dopaminergic neurons. Cerebellar optogenetic stimulations evoked similar movements in control and lesioned mice, suggesting a normal coupling of cerebellum to the motor effectors after the lesion. In freely moving animals, the firing rate in the primary motor cortex was decreased after the lesion, while cerebellar nuclei neurons showed an increased firing rate. This increase may result from reduced inhibitory Purkinje cells inputs, since a population of slow and irregular Purkinje cells was observed in the cerebellar hemispheres of lesioned animals. Moreover, cerebellar stimulations generated smaller electrocortical responses in the motor cortex of lesioned animals suggesting a weaker cerebello-cerebral coupling. Overall these results indicate the presence of functional changes in the cerebello-cerebral circuit, but their ability to correct cortical dysfunction may be limited due to functional uncoupling between the cerebellum and cerebral cortex.
在帕金森病中，中脑多巴胺能神经元的退化始终与小脑代谢活性的改变有关。在这里，我们研究了中脑多巴胺能神经元 6-OHDA 损伤的帕金森病小鼠模型中发生的小脑-大脑回路的功能重组。小脑光遗传学刺激在对照组和损伤组小鼠中引起类似的运动，表明小脑与运动效应器在损伤后正常耦合。在自由活动的动物中，损伤后初级运动皮层的放电率降低，而小脑核神经元的放电率增加。这种增加可能是由于抑制性浦肯野细胞输入减少所致，因为在损伤动物的小脑半球中观察到一群缓慢和不规则的浦肯野细胞。此外，小脑刺激在损伤动物的运动皮层中产生较小的电皮质反应，表明小脑-大脑耦合较弱。总的来说，这些结果表明小脑-大脑回路存在功能变化，但由于小脑和大脑皮层之间的功能去耦，它们纠正皮质功能障碍的能力可能受到限制。
