Influence of motor cortex on network activity and sensory processing in S1

描述（由申请人提供）：情境依赖性是感官知觉的基本属性;我们对外部世界的感知不是被动的，而是高度依赖于我们的内部状态（即注意力，欲望）和持续的行为。例如，如果我们感觉到有东西在指尖表面移动，那么在解释我们触摸的物体的性质时，必须知道是物体还是我们的手在移动。解剖学研究表明，新皮质的运动（运动）和感觉区域高度相互关联，但我们对来自运动皮质的信号如何影响感觉处理知之甚少。我们打算在网络和细胞水平的鼠标胡须系统，这是一个主要的方式，小鼠导航他们的周围环境，是类似于人类的触觉感觉系统的感觉运动的整合。通过使用最先进的光遗传学技术，我们能够控制运动皮层中神经元的活动，并测量躯体感觉皮层中的细胞和网络活动。我们已经收集了令人兴奋的初步数据，刺激运动皮层可以有效地改变感觉皮层中正在进行的网络活动，这反过来可能会增强感觉反应的可靠性。在这 在第一组实验中，我们打算建立一个机制的理解，运动皮层输入如何影响细胞的兴奋性和体感皮层的感觉反应。这些刺激研究将在麻醉小鼠中进行，其中运动和感觉通路可以在其他稳定和有节奏的网络动态中刺激。第二组实验将在清醒的小鼠中进行，以确定运动皮层输入在网络活动的局部调节中的重要性。通过刺激或抑制运动皮层的活动和记录多个感觉区域的网络活动，我们打算确定这种输入是否可以双向调节清醒小鼠网络活动的局部变化。这项研究可能有助于我们理解感觉加工的上下文依赖性，因此能够更好地理解感觉知觉和运动协调，可用作感觉加工的皮质-皮质调节的一般模型，并增强我们对ALS和中风中运动皮质损伤后皮质缺损的理解。

DESCRIPTION (provided by applicant): Context dependence is a fundamental property of sensory perception; our perception of the outside world is not passive, but highly dependent upon our internal state (i.e. attention, desire) and ongoing behavior. For instance, if we feel something moving across the surface of our fingertips, it essential to know whether it is the object or our hand that is moving, when interpreting the nature of the object we are touching. Anatomical studies have shown that the movement (motor) and sensory regions of neocortex are highly interconnected, yet we know little about how signals from motor cortex influence sensory processing. We intend to study this sensorimotor integration at the network and cellular levels in the mouse whisker system, which is one of the primary modalities by which mice navigate their surroundings and is analogous to the human tactile sensory system. By using state-of-the-art optogenetics technology we are able to control the activity of neurons in motor cortex and measure cellular and network activity in somatosensory cortex. We have gathered exciting preliminary data that stimulating motor cortex can effectively alter the ongoing network activity in sensory cortex, which may in turn enhance the reliability of sensory responses. In this proposal, in a first set of experiments we intend to establish a mechanistic understanding of how motor cortex inputs influence cellular excitability and sensory responses in somatosensory cortex. These stimulation studies will be conducted in anesthetized mice, where motor and sensory pathways may be stimulated in an otherwise stable and rhythmic network dynamic. A second set of experiments will be conducted in awake mice, in order to determine the importance of the motor cortex inputs in the local regulation of network activity. By stimulating o suppressing activity in motor cortex and recording network activity in multiple sensory regions, we intend to determine whether this input can bi-directionally regulate local changes in network activity in awake mice. This research may potentially contribute to our understanding of the context dependence of sensory processing, and therefore enable a better understanding of sensory perception and motor coordination, be used as a general model for cortico-cortical regulation of sensory processing, and enhance our understanding of cortical deficits following damage to motor cortex as in ALS and stroke.