Cerebellar Outputs Through an Unconventional Nucleus

小脑通过非常规核的输出

• 批准号: 9892504
• 负责人: Christopher Chen
• 金额: $ 9.49万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892504
• 关键词: Affect; Aggressive behavior; Amygdaloid structure; Anatomy; Animals; Area; Axon; Behavior; Behavioral; Brain; Brain region; Cell Nucleus; Cells; Cerebellar Cortex; Cerebellar Diseases; Cerebellar Nuclei; Cerebellum; Code; Cognition; Data; Development; Disease; Extinction (Psychology); Fright; Halorhodopsins; Head; Heart Rate; Human; In Vitro; Intervention; Label; Language; Lead; Learning; Link; Literature; Lobule; Location; LoxP-flanked allele; Mediating; Molecular Profiling; Motor; Movement; Mus; Mydriasis; Negative Valence; Neurons; Optics; Output; Pathway interactions; Phase; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Property; Prosencephalon; Proteins; Pupil; Purkinje Cells; Reaction; Rest; Role; Sleep; Socialization; Stimulus; Structure; Synapses; Synaptophysin; Testing; Tomatoes; Transgenic Animals; Trauma; Vestibular nucleus structure; Virus; Visceral; Work; autism spectrum disorder; awake; basal forebrain; conditioned fear; executive function; human imaging; imaging study; in vivo; novel; parabrachial nucleus; pre-clinical; prevent; reduce symptoms; relating to nervous system; response; selective expression; sensory stimulus

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.

小脑不再仅仅是一个运动结构。人类成像研究指出，小脑与认知、语言和情感之间存在联系。临床前研究还表明，小脑有许多非运动功能，从攻击到睡眠。自闭症相关蛋白在小脑主要神经元(浦肯野细胞)中的表达足以概括小鼠这种疾病的许多特征。这些浦肯野细胞将它们的投射发送到小脑深核(DCN)和前庭核(VN)，这两个核通常被认为是小脑唯一的输出核团。然而，已知的连接小脑和前脑的输出通路似乎不足以解释现在与之相关的各种行为。我们发现，通过臂旁核还有一条额外的、被低估的输出通路，它接受浦肯野细胞的直接输入，并投射到前脑。与传统的小脑输出不同，这条通路有重要的投射到杏仁核、基底前脑、前额叶皮质和其他部位。该项目的目的是表征小脑对臂旁核的输入，并确定这些新的小脑输出目标。我们将重点放在杏仁核的投射上。有丰富的行为学文献将小脑描述为恐惧消退的核心组成部分，尽管还没有已知的神经基础支持这一点。在人类中，小脑创伤是创伤后应激障碍的强烈预测因素。我们将测试这种非常规的小脑输出是否可能调节这种非运动行为。