Spontaneous Intrinsic Activity as a Window into Visual Cortical Circuits

描述（由申请人提供）：大脑皮层是我们感知、记忆和语言的主要部位，是自发活动的。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，在丘脑皮层切片的自发皮层活动的时空模式是类似的模式触发丘脑输入。这一结果表明，内在皮层连接主要驱动皮层反应的模式。然后，外部输入可以释放这种内在活动模式。然而，在整个大脑回路完整的体内验证这个模型是至关重要的。 提出的目标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的起点，解剖产生和调节这种活动的微电路。目的2将讨论自发活动模式与皮层对感觉输入的反应之间的关系。 为了实现这些目标，我们将利用头部固定的小鼠在空气浮动球形跑步机上成像清醒时的神经活动 行为老鼠我们将使用快速双光子钙成像技术以前所未有的精度测量体内大量神经元的活性。为了提供外部输入，将使用心理物理学工具在Matlab中生成视觉刺激。 这项工作将有助于区分大脑皮层的两种观点：要么主要由外部输入驱动，要么主要由内部电路驱动。这将是基础神经科学的一个进步，也与人类疾病有关。大脑皮层是人类所珍视的许多大脑功能的所在地，也是许多破坏性神经和精神疾病的目标。通过增加我们对皮质功能的理解，这个项目将有助于为理解导致人类如此多痛苦的皮质功能障碍奠定基础。

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.