Development of Persistent Repetitive Behavior in Animals

对异常重复行为的发展知之甚少（例如，刻板印象，仪式）的儿童在自闭症和相关的神经发育障碍的风险。这种知识的缺乏妨碍了有效的早期干预和预防战略。适当的动物模型可以提供大量关于这种行为的发育特征的信息，特别是介导向持久、固定和习惯性行为转变的神经生物学机制。因此，本项目的总体目标将是研究小鼠模型中重复运动行为的发展，并确定介导习惯性、持久性和不灵活运动行为的出现和表达的神经生物学机制。我们将检验持续性重复行为的发展与皮质-基底神经节回路改变有关的假设。具体来说，我们将检验基底神经节通路（直接和间接）（目标#2）以及纹状体区室（纹状体和基质）（目标#3）的改变介导向持续重复行为的转变的假设。目标2中的药理学实验不仅有助于确定神经生物学机制，而且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.