In-vivo control of information flow by artificial stimulation: ephys and behavior

描述（由申请人提供）：通过人工刺激对信息流的体内控制：ephys和行为大脑中的感觉通路用于提取和处理有关外部世界的信息，以便我们可以感知我们的环境并对我们的行为做出决定。 与运动控制相反，丰富的研究历史已经形成了将运动区域中的神经元群体活动与运动输出元素联系起来的基础，我们没有类似的一般框架来为感觉通路提供替代信号。 在大鼠触须系统中使用急性和清醒行为实验的组合，再加上皮层下模式化的电和光（光遗传学）刺激，皮层激活的电压敏感染料（VSD）成像，理想的观察者和信息理论分析，以及精确的感觉行为任务，我们独特地定位于开发一个框架，用于表征，优化，以及控制通过人工激活神经结构而诱导的感觉通路中的信息流。 本课题将1）利用丘脑的电刺激和光刺激，结合麻醉大鼠皮层的在体VSD成像，从皮层活动的理想观察者的角度评估一系列刺激的可检测性和可辨别性，并制定刺激设计的原则基础，以优化可辨别性，2）使用光遗传学技术通过背景去极化/超极化来操纵丘脑去极化/同步的水平，以形成电路的非线性响应特性并开发对输入组之间的可检测性和可辨别性水平的控制，以及3）开发用于在可检测性和可辨别性之间的权衡的人工操纵的行为框架，以优化在不同上下文中的性能。重要性：因此，开发人工手段来激活受损个体的感觉回路是一个极其重要的公共卫生问题，并且开发用于控制感觉通路中的信息流的原理是至关重要的，但目前还不存在。 此外，能够以精确的方式激活下游的大脑结构，对于研究神经元群体如何 代表信息以及这些代表如何在大脑区域传播-以理解神经代码。 创新：这里的概念创新是使用的性能之间的联系，一个理想的观察者的皮层活动和行为的设计和优化工具，人工刺激。 我们使用体内电生理学与多电极、多位点记录、电压敏感染料成像、模式化微刺激和光遗传学、高度特定的行为任务以及控制理论框架的创新组合，这些在科学界都不存在。

DESCRIPTION (provided by applicant): In-vivo control of information flow by artificial stimulation: ephys and behavior Sensory pathways in the brain exist to extract and process information about the outside world, so that we may perceive our environment and make decisions about our actions. In contrast to motor control, where a rich history of investigation has formed a foundation for linking neuronal population activity in motor regions to elements of motor output, we do not have an analogous general framework for providing surrogate signals to sensory pathways. Using a combination of acute and awake-behaving experiments in the rat vibrissa system, coupled with sub-cortical patterned electrical and optical (optogenetic) stimulation, voltage sensitive dye (VSD) imaging of cortical activation, ideal observer and information theoretic analyses, and precise sensory behavioral tasks, we are uniquely positioned to develop a framework for characterizing, optimizing, and controlling information flow in sensory pathways induced through artificial activation of neural structures. In this project, we will 1) utilize electrical and optical stimulation of the thalamus in conjunction with n-vivo VSD imaging in cortex of the anesthetized rat to assess the detectability and discriminability of a range of stimuli from the perspective of an ideal observer of cortical activiy, and formulate a principled basis for stimulation design for optimizing discriminability, 2) manipulate the level of thalamic depolarization/synchrony through background depolarization/hyperpolarization using optogenetic techniques to shape the nonlinear response properties of the circuit and develop control of the level of detectability and discriminability among sets of inputs, and 3) develop a behavioral framework for artificial manipulation of the trade-off between detectability and discriminability to optimize performance in different contexts. Significance: The development of artificial means by which to activate sensory circuits for impaired individuals is thus an extremely important public health issue, and the development of principles for controlling information flow in sensory pathways is of paramount importance, but currently does not exist. Furthermore, being able to activate downstream brain structures in a precise manner is also critical in the basic scientific investigation of how populations of neurons represent information and how these representations are propagated across brain regions - to understand the neural code. Innovation: The conceptual innovation here is the use of the link between performance of an ideal observer of cortical activity and behavior as a design and optimization tool for artificial stimulation. We use an innovative combination of in-vivo electrophysiology with multi-electrode, mult-site recording, voltage sensitive dye imaging, patterned microstimulation and optogenetics, highly specific behavioral tasks, and a control-theoretic framework, which together do not exist in the scientific community.