Nano- and Microelectronic Tools for Interrogating Neuronal Circuits and Networks

摘要：生物神经网络的功能是由其固有的特性决定的。 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 正如网络所通知的！S的电化信号时空格局。破译 神经元编码--时空连接转化为功能的规则--仍然是主要的 科学挑战，很大程度上是因为缺乏实验工具，使准备井- 具有受控连接的定义神经元电路和物理连接的同时映射 在许多神经元之间，并在这些神经元之间传播信号。本文提出的项目旨在开发新的 解决这些特殊问题的纳米和微电子工具。具体来说，我们将开发：(1)平面 膜片钳阵列(元件编号100，元件间距200？M)，可实时监测 分离培养或切片制备中的多个神经元以及(2)可扰动的垂直纳米线阵列 通过控制生物化学的引入改变神经元的分化和突触的形成 以特定于细胞的方式发出信号。然后，这些新工具将与光学激发和 成像方案，在局部和全局水平上探测组成神经元的实时动力学 基于精确定义的扰动的应用，在给定的神经元网络内。结合在一起，这些 Tools还将提供一个以并行方式分析生化和遗传途径的新平台 它们控制着神经元的分化和生长。这项拟议的研究结合了最近在 神经生物学在纳米材料合成和微制造方面的尖端发展，将使 仔细研究现有的网络连通性以及刺激和奖励诱导的突触适应。这个 通过这些研究获得的信息对于系统翻译任何网络都是至关重要的！S连通性 其功能，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.