Nano- and Microelectronic Tools for Interrogating Neuronal Circuits and Networks

翻译后摘要：生物神经元网络的功能是由其内在属性决定的， 组成神经元，它们的空间连接，以及这些连接的适应性加强/减弱 据网络报道！电子和化学信号的时空模式。破译 神经元编码-时空连接转换为功能的规则-仍然是一个主要的 科学的挑战，主要是由于缺乏实验工具，使两个良好的， 具有受控连接的定义的神经元回路和物理连接的同时映射 以及许多神经元之间的信号传播。本项目旨在开发新的 解决这些特殊问题的纳米和微电子工具。具体而言，我们将开发：（1）平面 膜片钳阵列（单元数> 100，单元间距< 200？m）能够实时监测 分离培养物或切片制备物中的多个神经元，以及（2）可以干扰神经元的垂直纳米线阵列。 并通过控制引入生物化学物质来改变神经元分化和突触形成 以细胞特有的方式传递信号。这些新工具将与光学激发结合使用， 成像方案，在局部和全局水平上探测组成神经元的实时动态 在一个给定的神经网络中应用精确定义的扰动。结合在一起，这些 工具也将提供一个新的平台，以平行的方式分析生物化学和遗传途径， 控制着神经元的分化和生长这项拟议中的研究结合了 神经生物学与纳米材料合成和微加工的前沿发展，将允许 细致的研究现存的网络连接和刺激和奖励诱导的突触适应。的 通过这些研究获得的信息对于系统地翻译任何网络都至关重要！s连接 它的功能，从而有助于解开大脑的设计原则。

Abstract: The function of a biological neuronal network is determined by the intrinsic properties of its constituent neurons, their spatial connectivity, and the adaptive strengthening/weakening of those connections as informed by the network!s spatiotemporal pattern of electrical and chemical signaling. Deciphering the neuronal code - the rules by which spatiotemporal connectivity translates to function - remains to be a major scientific challenge, largely due to the lack of experimental tools that enable both the preparation of well- defined neuronal circuits with controlled connections and the simultaneous mapping of physical connectivity among, and signal propagation between, many neurons. The project proposed herein aims to develop new nano- and microelectronic tools that address these particular issues. Specifically, we will develop: (1) planar patch-clamp arrays (element number > 100, element pitch < 200 ?m) that enable the real-time monitoring of multiple neurons in dissociated culture or slice preparations and (2) vertical nanowire arrays that can perturb and modify neuronal differentiation and synapse formation through the controlled introduction of biochemical signals in a cell-specific fashion. These new tools will then be used, in combination with optical excitation and imaging schemes, to probe, at both the local and global levels, the real-time dynamics of constituent neurons within a given neuronal network upon application of precisely defined perturbations. Combined together, these tools will also provide a new platform for assaying, in a parallel fashion, the biochemical and genetic pathways that govern neuronal differentiation and growth. The proposed research, which combines recent advances in neurobiology with cutting-edge developments in nanomaterials synthesis and microfabrication, will allow for the meticulous study of extant network connectivity and stimuli- and reward-induced synaptic adaptation. The information gained through these studies will be crucial for systematically translating any network!s connectivity to its function, and thus help to unravel the design principles of the brain.