Diversity of excitatory afferents to the cerebellar nuclei

项目总结 小脑是微调运动的关键。抑制性浦肯野细胞是影响 唯一的输出是小脑，小脑核团。很多人都知道， 浦肯野神经元塑造核输出。人们可能会认为小脑有核细胞只能在 浦肯野细胞暂停，然而浦肯野细胞-核细胞活动并不总是相反的，这表明 其他输入可能会驱动小脑的输出。在这里，我们将测试插入原子核(IN)可以 是由兴奋性传入驱动的，但浦肯野神经元设定了这一输入的增益。以下几个细微差别 将利用小脑前部传入解剖学来探索这一假说。来自逆行追踪的证据 研究表明，谷氨酸能运动前区，即支配运动的红核(RN) 脊髓中的结构，也支配着IN，不包括小脑皮质。这些RN-to-In 传入不同于典型的脑桥苔藓纤维传入，后者主要侧支支配两个IN 和覆盖的皮质。这些差异表明，RN在调节IN射速方面扮演着不同的角色。这里 我们将测试构成该功能的解剖学、生理学和行为学基础。 红脑小脑回路至小脑核团处理。该提案的第一个目标是测试RN如何 传入与皮层驱动的抑制相结合，以调节IN的输出。这项提议的第二个目标是 目的：研究红小脑传入神经在步态中协调肢体间运动中的作用。两者都是IN 和RN分别被证明参与肢体协调，但没有证据表明 红核小脑传入的特殊作用。最后，我们将研究红核小脑的信息传入是什么。 正在发送到IN。RN的两个主要输入来自IN本身和初级运动皮质)， 然而，红斑小脑细胞所特有的神经支配尚不清楚。加在一起，这些实验将成为 首先，研究一种特定的传入神经在调节小脑核活动中的作用。我们的研究将对我们有所帮助 阐明小脑核团整合传入的感觉和运动信息的机制 执行精确的定时动作。

PROJECT SUMMARY The cerebellum is critical for fine-tuning movement. Inhibitory Purkinje cells are a predominant influence on the sole output of the cerebellum, the cerebellar nuclei. A good deal is known about how inhibitory influence from Purkinje neurons shapes nuclear output. One might expect that cerebellar nuclear cells could only fire during Purkinje cell pauses, however Purkinje cell-nuclear cell activity are not always inversely related, suggesting other inputs may drive cerebellar output. Here, we will test the hypothesis that the interposed nucleus (IN) can be driven by excitatory afferents but that Purkinje neurons set the gain of this input. Several nuances of precerebellar afferent anatomy will be utilized to explore this hypothesis. Evidence from retrograde tracing studies suggests that the glutamatergic premotor area, the red nucleus (RN), which innervates motor structures in the spinal cord, also innervates the IN to the exclusion of the cerebellar cortex. These RN-to-IN afferents differ from canonical pontine mossy fiber inputs, which mainly collateralize to innervate both the IN and overlying cortex. These differences point to a differential role the RN has in modulating IN firing rate. Here we will test the anatomical, physiological and behavioral substrates that underlie the function of the rubrocerebellar circuitry to cerebellar nuclear processing. The first goal of this proposal is to test how RN afferents are integrated with cortical driven inhibition to modulate IN output. The second goal of this proposal is to examine the role of rubrocerebellar afferents in coordinating inter-limb movements during gait. Both the IN and RN have been shown separately to be involved in limb coordination but there is no evidence as to the specific role of rubrocerebellar afferents. Lastly, we will examine what information rubrocerebellar afferents are sending to the IN. The two major inputs to the RN originate from the IN itself and primary motor cortex), however what innervates rubrocerebellar cells specifically is unknown. Together, these experiments will be the first to examine the role of a specific afferent in modulating cerebellar nuclear activity. Our studies will help elucidate the mechanisms by which the cerebellar nuclei integrate incoming sensory and motor information to execute precisely timed movement.