Connectivity of the Posterior Cerebellum

小脑后部的连接

基本信息

批准号：
8911979
负责人：
Thomas John Pisano
金额：
$ 3.97万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-01 至 2020-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8911979
关键词：
Address Adult Affect Affective Algorithms Anatomy Anterior Architecture Area Autistic Disorder Behavior Behavior monitoring Behavioral Behavioral Assay Biological Models Blinking Brain Cerebellum Child Cognitive Color Communication Complement Congenital cerebellar hypoplasia Data Development Developmental Disabilities Diagnosis Disease Distant Engineering Equilibrium FDA approved Family Fluorescence Functional disorder G-Protein-Coupled Receptors Generations Genetic Incidence Injection of therapeutic agent Kainic Acid Knock-out Knowledge Label Life Ligands Lobule Methods Microscopic Midbrain structure Mind Molecular Monitor Movement Mus Muscimol Neurodevelopmental Disorder Neurologic Neurons Output Parietal Lobe Pathway interactions Patients Phenotype Physiological Play Prefrontal Cortex Primates Process Prosencephalon Relative (related person)Rest Role Sensory Social Interaction Specificity Structure Symptoms Synapses Testing Thalamic structure Therapeutic Tracer Triad Acrylic Resin Ventral Tegmental Area Viral Virus Work autism spectrum disorder base behavior influence cingulate cortex conditioning frontal lobe insight interest mouse model nervous system disorder new technology novel public health relevance receptor relating to nervous system skills

项目摘要

DESCRIPTION (provided by applicant): Autism spectrum disorder (ASD) represents a group of developmental disabilities characterized by the triad of repetitive actions, deficits in communication skills, and decreased interest in social interaction. ASD affects about 1 in 68 children, with the incidence of diagnosis increasing each year. A diagnosis of an ASD places a significant financial burden on the family. The pathophysiology of ASD is not well understood, there is no cure, and only two FDA-approved treatments exist-both of which only treat associated irritability and not the core Cerebellar irregularities and damage have been associated with ASD and other neurodevelopmental disorders. The cerebellum's output to the rest of the brain is exclusively through polysynaptic connections. Cerebellocerebral connections have remained poorly characterized from the lack transsynaptic neural tracers. Previous tracers only labeled one synapse effectively. Recently developed viral tracers are capable of transsynaptic spread, allowing for polysynaptic circuit characterization. One such tracer, the brainbow virus, changes fluorescence color in neurons expressing Cre, allowing for the discernment of pathway intermediaries. This proposal will use viral tracers to characterize the polysynaptic projections and intermediaries of cerebellar lobules VI and VII; lobules associated with nonmotor functions of the cerebellum and hence may have ASD significance. Studying long distance brain connections offers understanding of how distant brain areas influence each other and can provide insight into neurological disorders. After identifying the connections of lobules VI and VII, their influence on behavior will be explored. The new technology, DREADDs, allows for the temporal and spatial inactivation of neurons. DREADDs will be used to explore behavioral changes that result from the disruption of neuronal activity in lobules VI and VII. Behavioral assays commonly used to test autistic model mice: eyeblink conditioning, the three-chambered task, and the T-maze reversal task, will be used to detect qualities associated with autism in the DREADD-expressing mice. Notably, these mice will not be genetic knockouts; therefore, if autism-associated behaviors are observed it will implicate a cerebellar role in autism. This knowledge can provide novel avenues for both ASD diagnosis and therapeutics. symptoms of ASD.

描述（由申请人提供）：自闭症谱系障碍 (ASD) 是一组发育障碍，其特征为重复性行为、沟通缺陷和社交互动兴趣下降，大约每 68 名儿童中就有 1 人患有自闭症谱系障碍 (ASD)，其发病技能也很差。自闭症谱系障碍 (ASD) 的诊断数量逐年增加，给家庭带来了沉重的经济负担。自闭症谱系障碍 (ASD) 的病理生理学尚不清楚，无法治愈，并且只有两种经 FDA 批准的治疗方法 - 两者都只能治疗相关疾病。易激惹而非核心小脑不规则和损伤与自闭症谱系障碍和其他神经发育障碍有关。小脑向大脑其他部分的输出完全是通过多突触连接进行的，因为以前仅缺乏跨突触神经示踪剂。最近开发的病毒示踪剂能够跨突触传播，从而能够对多突触回路进行表征。脑弓病毒会改变表达 Cre 的神经元的荧光颜色，从而识别通路中介体。该提案将使用病毒示踪剂来表征与小脑非运动功能相关的小脑小叶 VI 和 VII 的多突触投射和中介体；研究远距离大脑连接可以了解远距离大脑区域如何相互影响，并可以在确定小叶 VI 和小叶的连接后深入了解神经系统疾病。 VII，将探索新技术 DREADD，允许神经元的时间和空间失活，以探索因小叶神经元活动破坏而导致的行为变化。通常用于测试自闭症模型小鼠：眨眼条件反射、三室任务和 T 迷宫逆转任务，将用于检测表达 DREADD 的小鼠中与自闭症相关的品质。值得注意的是，这些小鼠不会被基因敲除；因此，如果观察到与自闭症相关的行为，则表明小脑在自闭症中发挥作用，这一知识可以为自闭症谱系障碍的诊断和治疗提供新的途径。