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

描述(申请人提供)：通过人工刺激在体内控制信息流：大脑中存在眼球和行为感觉通路，以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动做出决定。与运动控制不同的是，丰富的研究历史为将运动区的神经元群体活动与运动输出元素联系起来奠定了基础，而我们没有类似的一般框架来向感觉通路提供替代信号。通过结合大鼠触觉系统中的急性和清醒行为实验，再加上皮质下图案化的电和光(光遗传)刺激、皮质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，我们处于独特的地位，可以开发一个框架来描述、优化和控制通过人工激活神经结构诱导的感觉通路中的信息流。在这个项目中，我们将1)利用丘脑的电和光刺激，结合n-vivo VSD在麻醉大鼠皮质中的成像，从理想的皮质活动观察者的角度评估一系列刺激的可检测性和可区分性，并为优化可识别性的刺激设计制定原则基础；2)使用光遗传技术通过背景去极化/超极化来操纵丘脑的去极化/同步水平，以形成电路的非线性响应特性，并对输入集合之间的可检测性和可区分度进行控制；以及3)开发一个行为框架，用于人工操纵可检测性和可区分性之间的权衡，以优化不同环境下的性能。意义：因此，开发人工方法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，而制定控制感觉通路中的信息流的原则是至关重要的，但目前还不存在。此外，能够以一种精确的方式激活下游的大脑结构，在神经元群体的基础科学研究中也是至关重要的。 表示信息，以及这些表示如何跨大脑区域传播--以理解神经代码。创新：这里的概念创新是利用理想的大脑皮层活动观察者的表现与行为之间的联系，作为人工刺激的设计和优化工具。我们使用了体内电生理学与多电极、多点记录、电压敏感染料成像、图案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，这些都是科学界所不存在的。

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.