Spontaneous Intrinsic Activity as a Window into Visual Cortical Circuits

描述（由申请人提供）：大脑皮层，我们感知、记忆和语言的主要部位，自发地活跃。虽然这种内在活动通常被认为是“噪音”，但最近的研究表明，它是理解皮层功能的关键秘密。值得注意的是，在丘脑皮层切片中，自发皮层活动的时空模式与丘脑输入触发的模式相似。这一结果表明，内在的皮层连通性主要驱动皮层反应的模式。外部输入可能会释放这种内在的活动模式。然而，在整个脑回路完好无损的体外验证这一模型至关重要。提出的目的1将确定在完整的大脑自发皮层活动的时空模式。确定体内自发活动的模式将是未来研究剖析产生和调节这种活动的微电路的起点。目的2将讨论自发性活动模式如何与皮层对感觉输入的反应相关。为了实现这些目标，我们将利用头部固定的鼠标在空气漂浮的球形跑步机上来成像清醒时的神经活动

DESCRIPTION (provided by applicant): The cerebral cortex, the primary site for our perception, memory, and language, is spontaneously active. While this intrinsic activity is often considered "noise," recent work suggests that it holds a key secret for understanding cortical function. Remarkably, in thalamocortical slices the spatiotemporal patterns of spontaneous cortical activity are similar to the patterns triggered by thalamic input. This result suggests tha intrinsic cortical connectivity primarily drives the pattern of the cortical response. External inpt may then release this intrinsic activity pattern. However, it is crucial to validate this model in ivo where entire brain circuits are intact. The proposed Aim 1 will determine the spatiotemporal patterns of spontaneous cortical activity in the intact brain. Determining the pattern of spontaneous activity in vivo will be a starting point for future studies dissecting the microcircuiry that generates and modulates this activity. Aim 2 will address how the spontaneous activity pattern is related to the cortical response to sensory input. To achieve these aims, we will utilize a head-fixed mouse on an air-floating spherical treadmill to image neural activity in awake behaving mice. We will use fast two-photon calcium imaging to measure the activity of large populations of neurons in vivo with unprecedented precision. To deliver external inputs, visual stimulation will be generated in Matlab using the Psychophysics Toolbox. This work will help to distinguish between two views of the cortex: either primarily driven by external inputs or primarily driven by internal circuitry. This will be an advance in basic neuroscience and also relevant to human disease. As the site of so many of the brain functions that humans hold dear, the cortex is also the target of many devastating neurologic and psychiatric diseases. By increasing our understanding of cortical function, this project will help lay the foundation for understanding the cortical dysfunction that underlies so much human suffering.