CRCNS US-German-Israeli Research Proposal: Multi-Level Neuro-Computational Models of Basal Ganglia Dysfunction in Tourette Syndrome

图雷特综合征是一种神经系统疾病，其特征是突然的运动和发声，称为抽搐。 这种疾病可以是高度衰弱的，具有严重的临床和社会影响。 这项工作的总体目标是联合收割机的实验和计算方法，以更好地了解机制，导致抽搐生产。 在过去的研究中，抽搐的产生与大脑不同区域的异常活动有关，其中许多区域位于基底神经节。 动物实验表明，阻断基底神经节神经元之间的某些形式的信号传导会诱发抽搐。 该项目将使用创新的方法从这些产生抽动的动物模型中的基底神经节神经元收集数据，这些数据将以多种方式使用。 数据分析将确定与抽搐产生相关的神经活动的变化，提供所涉及的神经元相互作用的详细视图。这些数据还将指导两个新的计算模型网络的开发，一个是集中的，一个是大规模的。 这些模型将用于探索基底神经节内神经元之间以及基底神经节与皮质中主要运动指挥中心之间的信号变化如何导致抽搐产生。 这些计算研究的结果将为后续的实验测试提供预测。 对于一个要执行的动作，它必须从无数可能的动作中选择。 目前还不清楚这种动作选择是如何完成的。 这个项目将提高我们对神经元活动和信号传导的变化如何导致抽搐产生以及一般行为选择的理解。关于抽动产生的结果将通过建议干预目标和提供测试潜在治疗影响的框架对Tourette综合征具有临床意义。目前，这样一个框架在该地区的抽动秽语综合征是缺乏的，相关的计算研究已经相当有限。开发的模型还将通过作为与神经元活动和运动相关脑区神经元之间信号传导相关的其他问题的研究资源来推进该领域。 同伴项目由德国联邦教育和研究部（BMBF）和美国-以色列两国科学基金会（BSF）资助。

Tourette syndrome is a neurological disorder characterized by sudden movements and vocalizations known as tics. The disorder can be highly debilitating with severe clinical and social effects. The overall goal of this work is to combine experimental and computational approaches to better understand the mechanisms leading to tic production. In past work, tic production has been linked to abnormal activity in a variety of brain regions, many of which are in an area called the basal ganglia. Experiments in animals have shown that blocking certain forms of signaling between neurons in the basal ganglia induces tics. This project will use innovative methods to collect data from neurons in the basal ganglia in these tic-producing animal models, which will be used in several ways. Data analysis will identify changes in neural activity that are linked with tic production, providing a detailed view of the neuronal interactions involved. The data will also guide the development of two novel computational model networks, one focused and one large-scale. These models will be used to explore how changes in signaling between neurons within the basal ganglia, as well as between the basal ganglia and major motor command centers in the cortex, can lead to tic production. Results of these computational studies will yield predictions for subsequent experimental testing. For an action to be performed, it must be selected from among the myriad of possible movements that could be made. How this action selection is accomplished is currently not well understood. This project will enhance our understanding of how changes in neuronal activity and signaling lead to tic production, as well as to the selection of actions in general. The results about tic production will have clinical implications for Tourette syndrome by suggesting targets for interventions and providing a framework for testing the impact of potential treatments. Currently, such a framework in the area of Tourette syndrome is lacking, and related computational studies have been quite limited. The models developed will also advance the field by serving as resources for the study of additional questions relating to neuronal activity and to signaling between neurons in movement-related brain areas. Companion projects are being funded by the Federal Ministry of Education and Research, Germany (BMBF), and the US-Israel Binational Science Foundation (BSF).