Cerebellar Outputs Through an Unconventional Nucleus

小脑不再仅仅是一个运动结构。人类成像研究指出了小脑与认知、语言和情感之间的联系。临床前工作也表明，小脑有许多非运动功能，从攻击到睡眠。孤独症相关蛋白在小脑主神经元（浦肯野细胞）中的表达足以概括小鼠孤独症的许多特征。这些浦肯野细胞将其投射到小脑深部核（DCN）和前庭核（VN），通常被认为是唯一的小脑输出核。然而，连接小脑和前脑的已知输出通路似乎不足以解释现在与之相关的行为多样性。我们发现，通过臂旁核有一个额外的、未被充分认识的输出通路，它接受直接的浦肯野细胞输入并投射到前脑。与传统的小脑输出不同，这条通路对杏仁核、基底前脑、前额皮质和其他部位有显著的投射。这个项目的目的是表征小脑输入臂旁和识别这些新的小脑输出目标。我们将重点关注杏仁核的投影。有大量的行为学文献将小脑描述为恐惧消退的核心组成部分，尽管没有已知的神经基质支持这一点。在人类中，小脑创伤是创伤后应激障碍的一个强有力的预测指标。我们将测试这种非常规的小脑输出是否可能介导这种非运动行为。

The cerebellum is no longer just a motor structure. Human imaging studies have pointed to links between the cerebellum and cognition, language, and affect. Preclinical work has also indicated that the cerebellum has many nonmotor functions ranging from aggression to sleep. Expression of autism related proteins within cerebellar principle neurons (Purkinje cells) is sufficient to recapitulate many hallmarks of the condition in mice. These Purkinje cells send their projections to the deep cerebellar nuclei (DCN) and vestibular nuclei (VN), often considered the only cerebellar output nuclei. However, the known output pathways that connect the cerebellum with the forebrain seem insufficient to explain the diversity of behaviors now associated with it. We found that there is an additional, underappreciated output pathway through the parabrachial nucleus that receives direct Purkinje cell input and projects to the forebrain. Unlike the conventional cerebellar outputs, this pathway has significant projections to the amygdala, basal forebrain, prefrontal cortex and others. The aim of this project is to characterize cerebellar inputs to the parabrachial and identify these novel cerebellar output targets. We will focus on the projection to the amygdala. There is a rich behavioral literature describing the cerebellum as a core component in fear extinction, though there is no known neural substrate underlying this. In humans, trauma to the cerebellum is a strong predictor of post- traumatic stress disorder. We will test whether this unconventional cerebellar output can potentially mediate this nonmotor behavior.