Dynamics and Control of Neuronal Pattern Formation

描述(申请人提供)：在过去的20年里，图案形成的物理学取得了巨大的进步。然而，将这种知识应用于神经系统的能力受到了我们对神经元相互作用动力学的了解，以及我们缺乏控制这种模式的系统参数的限制。在这次K02的前一段时间里，我们已经证明了电场可以作为反馈参数来自适应地控制神经元活动的模式。此外，我们已经证明，当单个神经元形成这些模式时，它们之间的相互作用可以被详细地描述。这一更新建议将寻求检验这样一个假设，即通过电场反馈可以实现神经元模式的参数控制。这种反馈可以作为一个基本的工具来探索神经元集合如何动态地形成和改变它们的活动模式，以及作为一种与病理神经元动力学相互作用和选择性地修改的手段。我的研究目标是开发神经元活动模式的智能交互和控制策略，使用物理学模式形成的框架来组织理论和实验。我提出了一个由四部分组成的方法：1)体外实验，以确定神经元之间的细胞内相互作用如何决定模式之间转换的性质，2)开发一个分区计算框架来直接对这些实验进行建模，3)开发抽象模型来理解这些现象背后的非平衡模式形成物理，以及4)应用从建模中获得的见解来设计和测试在体外和体内实验中癫痫发作和theta节律的合理控制策略。我的职业目标是利用K02机制密集地获得足够的图案形成物理学背景，通过1)正式的研究生工作，2)继续我的学习和与高级数学家和物理学家的合作，以及3)组织研讨会，进一步发展和扩大物理和医学的图案形成领域。

DESCRIPTION (provided by applicant): The physics of pattern formation has made dramatic strides over the past 20 years. Nevertheless, the ability to apply this knowledge to neuronal systems has been limited by our knowledge of the dynamics of neuronal interactions, and our lack of a system parameter to control such patterns. Over the previous period of this K02, we have demonstrated that electric fields can serve as a feedback parameter to control patterns of neuronal activity adaptively. Furthermore, we have demonstrated that the interactions between individual neurons as they form these patterns can be characterized in detail. This renewal proposal will seek to test the Hypothesis that parametric control of neuronal patterns can be achieved with electric field feedback. Such feedback can serve as a basic tool to explore how neuronal ensembles dynamically form and change their patterns of activity, and as a means to interact with and selectively modify pathological neuronal dynamics. My research goals are to develop intelligent interaction and control strategies for neuronal patterns of activity, using the framework of Pattern Formation in Physics to organize theory and experiments. I propose a 4 part approach: 1) In Vitro experiments to determine how the intracellular interactions between neurons determine the nature of the transition between patterns, 2) develop a compartmental computational framework to directly model these experiments, 3) develop abstract models to understand the nonequilibrium pattern formation physics that underlie these phenomena, and 4) to apply insights gained from modeling to design and test rational control strategies for seizures and theta rhythm in In Vitro and In Vivo experiments. My career goals are to use the K02 mechanism to intensively acquire a sufficient background in pattern formation physics to perform these proposed experiments through 1) formal graduate course work, 2) continuing my studies and collaboration with senior mathematicians and physicists, and 3) organizing workshops to further develop and expand the field of pattern formation in physics and medicine.