CAREER: Functional Replacement of Neural Tissue in a Model Organism - Research and Education in Neuroengineering

0348338 Butera神经工程学的主要目标是开发“替换部件”，即能够恢复、修改或增强神经功能的半导体电路和/或活组织的工程结构。大多数关于这一主题的研究都集中在无脊椎动物的小定义的神经回路或在体外或体内哺乳动物神经回路的大规模动态。这一综合研究和教育计划的目标是在上述两个极端之间建立一个中间地带：为一个具有充分研究的神经系统的简单生物体（海洋软体动物加利福尼亚海蛞蝓）开发一个“替代神经节”。工作重点是功能硬件替代品的表征和开发，有意不关注植入物和生物相容性方面。目标将通过五个相互关联的目标分为三类来实现：教育（E1和E2），研究（R1和R2）和技术开发（T1）。E1：开发和测试课程模块，用于向本科工程专业学生教授“批判性思维”技能。我们的假设是，大多数改善工程教育的努力并不直接解决这个问题，而这些技能对于工程师与生命科学家接触的多学科领域（如神经工程）是至关重要的。 研究人员计划通过调整现有的批判性思维练习和文本来解决这个问题。E2：开发补充实验室模块，用于向工程专业学生教授电生理学基础知识。这一目标将填补一些空白，在现有的文献本科生理学实验室，对工程专业的学生教学的偏见。在一个典型的3小时的工程实验室的约束内拟合，这些实验室模块必须是紧凑的，便携式的，并且能够在3小时或更短的时间内从开始到完成实施。R1：行为状态的表征和与腹神经节活动的相关性在加利福尼亚州阿鲁西亚。该目标有三个研究：行为监测系统的开发，称为行为表型分析的算法的设计，以及使用该监测系统同时在体内记录传入/传出腹神经节的神经活动。 研究人员假设一组模型参数（表型）可以定义正常的生理行为，并且该模型可以用于识别病理行为。R2：设计并实现腹神经节的输入/输出特性的实时模型，并与自由行为的失智症接口。该目标有三项研究：腹神经节的输入/输出特性的体外表征，这些输入/输出特性的实时模型的开发（在目标T1中设计的架构上）以及通过与自由行为的失智症接口来测试该模型。研究人员假设，由腹神经节控制的自主神经系统的正常生理功能反映在表现出“正常”行为的动物中。第一阶段：开发一种新型的实时计算平台，能够处理多达8个通道的同时输入/输出，具有足够的计算能力来实现基于“黑盒”内核的神经元模型以及模拟整个神经元群体动态的生物物理神经元模型。这种架构的设计具有模型/电路规格的灵活性和处理多通道高吞吐量数据的能力，并且基于现场可编程门阵列（FPGA）的使用。

0348338ButeraA primary goal in neuroengineering is the development of "replacement parts," engineered constructs of semiconductor circuits and/or living tissue that are capable of restoring, modifying, or enhancing neural function. Most research on this topic is focused on either small defined neural circuits in invertebrates or the large scale dynamics of in vitro or in vivo mammalian neural circuits. The objective of this integrated research and education plan is to forge a middle ground between the above two extremes: to develop a "replacement ganglion" for a simple organism with a well-studied nervous system (the marine mollusc Aplysia Californica). Efforts are focused on the characterization and development of a functional hardware replacement, and intentionally are not focused on the implant and biocompatibility aspects. Objectives will be accomplished through five inter-related aims broken down into 3 categories: education (E1 and E2), research (R1 and R2), and technology development (T1).E1: Development and testing of course modules for teaching "critical thinking" skills to undergraduate engineering students. The assumption is that most efforts at improving engineering education do not directly address this issue, and that such skills are critically necessary for multidisciplinary fields where engineers interface with life scientists, such as neuroengineering. The investigators plan to address this issue by adapting existing critical thinking exercises and texts to engineering students. E2: Development of complementary laboratory modules for teaching electrophysiology fundamentals to engineering students. This aim will fill some gaps in the existing literature on undergraduate physiology labs, with a bias towards teaching engineering students. Fitting within the constraints of a typical 3 hour engineering lab, these lab modules must be compact, portable, and capable of being implemented from start to completion in 3 hours or less. R1: Characterization of behavioral states and correlation with abdominal ganglion activity in Aplysia Californica. This objective has three studies: the development of a behavioral monitoring system, design of algorithms called behavioral phenotyping, and the use of this monitoring system with concurrent in vivo recording of neural activity passing in/out of the abdominal ganglion. The investigators hypothesize that a set of model parameters (the phenotype) can define normal physiologicsal behavior and this model can be utilized to identify pathological behavior. R2: Design and implementation of a real-time model of the input/output properties of the abdominal ganglion and interfacing to freely behaving Aplysia. This objective has three studies: in vitro characterization of the input/output properties of the abdominal ganglion, the development of a real-time model of these input/output properties (on the architecture to be designed in aim T1) and the testing of this model by interfacing to a freely behaving Aplysia. The investigators hypothesize that normal physiological function of the autonomic systems controlled by the abdominal ganglion is reflective in the animal exhibiting "normal" behavior. T1: To develop a novel real-time computational platform capable of processing up to 8 channels of simultaneous input/output, with sufficient computational power to implement both "black box" kernel-based as well as biophysical neuron models that model the dynamics of an entire neuron population. This architecture is designed for flexibility in model/circuit specification and the ability to handle multiple channels of high throughput data, and is based on the use of field-programmable gate arrays (FPGAs).