Context-dependent changes in local and long-range cortical circuits

描述（由申请人提供）：中枢神经系统的主要目的是使动物能够产生适当的行为输出。为了做到适当，动物必须同时考虑外部（感官）输入和内部（动机）状态。最近的观察表明，这些内部状态的神经元表示是目前在感觉处理的相对早期阶段。此外，这些内部状态可能会通过调节皮层回路的功能特性，从根本上改变感觉信息的处理方式。然而，突触和电路机制背后的这种上下文相关的处理感觉信息是未知的。此外，由于这些变化发生在快速的时间尺度上，标准的体外方法研究可塑性的细胞机制是不合适的。相反，这个问题需要新的方法来监测清醒的行为动物的突触连接和强度。因此，我们将开发新的策略，并结合联合收割机现有的，以解决如何皮层电路动态地重新配置内部状态。特别是，新开发的头固定啮齿动物的视觉引导行为，使小鼠视觉系统的一个有用的模型来研究这个问题。该提案建立在这些行为进步的基础上，并将其与其他现代方法相结合，包括体内双光子钙成像，单细胞刺激和全细胞电生理学，以直接测量初级视觉皮层中的神经元网络如何在行为过程中被修改。这种新颖的技术组合将揭示如何参与依赖于不同视觉特征检测的任务，改变视觉皮层内的功能连接。此外，我们将使用新开发的方法来成像皮质-皮质轴突投射中的感觉反应，以确定行为背景如何影响感觉信息向更高视觉区域的传输。这些实验将确定突触和电路机制，这些机制是网络活动中依赖于上下文的变化的基础，从而实现对活跃工作大脑中感觉处理的全新理解。

DESCRIPTION (provided by applicant): The main purpose of the central nervous system is to enable animals to generate appropriate behavioral outputs. In order to be appropriate, the animal must take into account both external (sensory) inputs as well as internal (motivational) states. Recent observations suggest that neuronal representations of these internal states are present at relatively early stages in sensory processing. Moreover, these internal states may fundamentally change the way that sensory information is processed by modulating the functional properties of cortical circuits. Yet, the synaptic and circuit mechanisms underlying thi context-dependent processing of sensory information are not known. Moreover, since these changes occur on rapid time scales, standard in vitro methods for investigating the cellular mechanisms of plasticity are not appropriate. Instead, this question requires new approaches for monitoring synaptic connectivity and strength in the awake, behaving animal. Thus, we will develop new strategies, and combine existing ones, to address how cortical circuits are dynamically reconfigured by internal state. In particular, newly developed visually-guided behaviors for headfixed rodents have made the mouse visual system a useful model to study this problem. This proposal builds on these behavioral advances, and combines them with other modern methods including in vivo two-photon calcium imaging, single-cell juxtacellular stimulation, and whole-cell electrophysiology to directly measure how neuronal networks in primary visual cortex are modified during behavior. This novel combination of techniques will reveal how engagement in tasks which rely on the detection of distinct visual features alter the functional connectivity within visual cortex. In addition, we will use newly developed approaches to image the sensory responses in cortico-cortical axonal projections to determine how behavioral context impacts the transmission of sensory information to the higher visual areas. These experiments will identify synaptic and circuit mechanisms that underlie context-dependent changes in network activity, thereby achieving a fundamentally new level of understanding of sensory processing in the actively working brain.