Development of Persistent Repetitive Behavior in Animals

关于自闭症和相关神经发育障碍风险儿童的异常重复行为(例如，刻板印象、仪式)的发展情况，人们知之甚少。由于缺乏知识，因此无法采取有效的早期干预和预防战略。合适的动物模型可以提供关于这种行为的发育特征的丰富信息，特别是调节向持续、固定和习惯性行为转变的神经生物学机制。因此，该项目的总体目标将是在小鼠模型中检查重复运动行为的发展，并确定调节习惯性、持续性和僵硬运动行为出现和表达的神经生物学机制。我们将检验假设，即持续性重复行为的发展与Corti共同基底节回路的改变有关。具体地说，我们将测试假设，即基底节通路(直接和间接)(目标2)以及纹状体隔室(纹状体和基质)(目标3)的改变介导了向持续重复行为的转变。AIM#2中的药理学实验不仅将有助于确定神经生物学机制，还将确定药物开发的潜在治疗靶点。

Little is known about the development of abnormal repetitive behaviors (e.g., stereotypies, rituals) in children at risk for autism and related neurodevelopmental disorders. This lack of knowledge precludes effective early intervention and prevention strategies. Appropriate animal models could provide a wealth of information about the developmental characteristics of such behavior, particularly the neurobiological mechanisms mediating the transition to persistent, fixed, and habitual behavior. Thus, the overall goal of this project will be to examine the development of repetitive motor behavior in a mouse model and identify the neurobiological mechanisms mediating the emergence and expression of habitual, persistent and inflexible motor behavior. We will test hypotheses that the development of persistent repetitive behavior is associated with alterations in corti co-basal ganglia circuitry. Specifically, we will test hypotheses that alterations in basal ganglia pathways (direct and indirect) (Aim #2) as well as striatal compartments (striosome and matrix) (Aim #3) mediate the transition to persistent repetitive behavior. Pharmacological experiments in Aim #2 will not only aid in identifying neurobiological mechanisms but will also identify potential therapeutic targets for drug development.