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

描述（由申请人提供）：通过人工刺激在体内控制信息流：神经和行为大脑中存在的感觉通路，用于提取和处理有关外界的信息，从而使我们能够感知我们的环境并对我们的行为做出决定。与运动控制相比，丰富的研究历史已经形成了将运动区域的神经元群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。结合大鼠触颤系统的急性和清醒行为实验，结合皮层下模式电和光学（光遗传）刺激，皮层激活的电压敏感染料（VSD）成像，理想观察者和信息理论分析，以及精确的感觉行为任务，我们具有独特的优势，可以开发一个框架，用于表征，优化，通过人工激活神经结构来控制感觉通路中的信息流。在本项目中，我们将1)利用丘脑的电刺激和光学刺激，结合麻醉大鼠皮层的活体VSD成像，从一个理想的皮层活动观察者的角度评估一系列刺激的可探测性和可辨别性，并制定刺激设计的原则基础，以优化可辨别性；2)利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/同步水平，以塑造电路的非线性响应特性，并在输入集之间建立可检测性和可判别性水平的控制；3)建立人工操纵可检测性和可判别性之间权衡的行为框架，以优化不同环境下的性能。意义：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，而控制感觉通路信息流的原则的发展是至关重要的，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，对于研究神经元群是如何形成的基础科学研究也至关重要

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.