Diversity of excitatory afferents to the cerebellar nuclei

项目摘要 小脑对于微调运动至关重要。抑制性浦肯野细胞是一个主要的影响， 小脑的唯一输出，小脑核。关于抑制性影响是如何从 浦肯野神经元塑造核输出。人们可能会认为小脑核细胞只有在 浦肯野细胞暂停，然而浦肯野细胞-核细胞活性并不总是负相关，这表明 其他输入可以驱动小脑输出。在这里，我们将测试的假设，即插入核（IN）可以 由兴奋性传入驱动，但浦肯野神经元设置了这种输入的增益。几个细微差别 小脑前传入解剖将被用来探讨这一假设。逆行追踪的证据 研究表明，运动前区，红核（RN），神经支配运动， 脊髓中的神经结构也支配IN，排除小脑皮质。这些RN到IN 传入与典型的脑桥苔藓纤维传入不同，后者主要通过侧支来神经支配IN 和覆盖的皮层。这些差异表明RN在调节IN放电率方面具有不同的作用。这里 我们将测试的解剖，生理和行为基板的功能基础， 红核小脑回路到小脑核处理。本提案的第一个目标是测试RN如何 传入与皮质驱动的抑制相结合以调节IN输出。该提案的第二个目标是 研究红核小脑传入神经在步态中协调肢体间运动的作用。无论是在 和RN分别被证明参与肢体协调，但没有证据表明 红核小脑传入神经的特殊作用。最后，我们将研究什么是信息红核小脑传入 发送到IN。RN的两个主要输入来源于IN本身和初级运动皮层）， 然而，究竟是什么具体地支配红核小脑细胞还不清楚。总之，这些实验将成为 第一次检查的作用，一个特定的传入调节小脑核活动。我们的研究将有助于 阐明小脑核整合传入的感觉和运动信息的机制， 执行精确的定时运动。

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.