Methodologically-Integrated Approaches Linking Cell Types to Neural Circuits and Function

项目摘要 要了解产生感知和行为的电路机制，需要将神经元 从活动到连接。这可以在多个比例下完成，并且理想情况下可以与进一步的 使用活动操纵来证明因果关系的研究。最近在鼠标视觉系统方面的工作已经完成 揭示了特定细胞类型对视觉感受野特性产生的贡献以及 视觉信息呈现的状态依赖变化。但目前尚不清楚大脑皮层 在老鼠身上揭示的电路机制和原理在不同物种之间被保存下来。 该项目旨在开发和提炼分子、遗传、病毒和大规模光学和电学 用于非啮齿动物皮质的记录工具。将建立这些工具可以链接的范例 大脑皮质模块、细胞类型和连接性的视觉功能。扩大角色知识的实验 要与在小鼠身上收集的数据相比较，需要特定的皮质细胞类型来评估 单元类型特定计算的常见电路机制和原理与 专门化的专用于特定物种或功能的在指挥的同时系统地控制视觉刺激 使用这些工具记录活动将创建数据集，使其能够测试原理和 从对小鼠皮质的研究中发现的特定回路基序的功能可以推广到更高层次 物种。 特定的目标围绕视觉诱发活动将与之相关联的选择性水平来组织 电路：1)模块，2)单元类型，3)连接。这些目标共享两种不同的基本方法 记录大神经元群体的动态活动--双光子钙成像和高密度 (128和384通道)层状硅胶电极阵列。目标1将视觉诱发的神经元活动与 初级视皮层的模块化和层状组织(V1)。这种知识可以与已知的知识相结合 连接和模块化/层状组织之间的关系，以便将电路链接到功能。目标2将链接 视觉诱发V1细胞类型的神经元活动：结合双光子钙成像和尸检 用高密度层状电极鉴定和抗体染色；记录单个神经元的活动 阵列，然后根据电子图像识别细胞类型。目标3将直接链接到视觉唤起 利用记录的多达150个神经元的记录进行互相关分析的神经元活动与连接性 同时采用高密度层状电极阵列。

Project Summary Understanding the circuit mechanisms that give rise to perception and behavior requires linking neuronal activity to connectivity. This can be accomplished at multiple scales and ideally can be related to further studies using activity manipulations to demonstrate causality. Recent work in the mouse visual system has revealed the contributions of specific cell types to the generation of visual receptive field properties as well as state-dependent changes in the representation of visual information. But it is unknown whether the cortical circuit mechanisms and principles revealed in the mouse are preserved across species. This project aims to develop and refine molecular, genetic, viral and large scale optical and electrical recording tools for use in the non-rodent cortex. Paradigms will be established by which these tools can link visual function to cortical modules, cell types, and connectivity. Experiments that expand knowledge of the role of specific cortical cell types to be comparable to data collected in mice are required to evaluate what are common circuit mechanisms and principles of cell type specific computations versus circuits that are specialized to particular species or functions. Systematically controlling visual stimuli while conducting recordings of activity with these tools will create data sets that make it possible to test whether principles and functions of specific circuit motifs emerging from studies in the mouse cortex can be generalized to higher species. Specific aims are organized around levels of selectivity at which visually-evoked activity will be linked to circuits: 1) modules, 2) cell types, and 3) connectivity. These aims share two different basic approaches for recording dynamic activity from large neuronal populations – two-photon calcium imaging and high-density (128 and 384 channel) laminar silicone electrode arrays. Aim 1 will link visually evoked neuronal activity to modular and laminar organization of primary visual cortex (V1). This knowledge can be combined with known relationships between connectivity and modular/laminar organization to link circuits to function. Aim 2 will link visually evoked neuronal activity to V1 cell types by: combining 2-photon calcium imaging with post mortem identification and antibody staining; and recording activity of single neurons with high-density laminar electrode arrays and then identifying cell types based on electrical images. Aim 3 will directly link visually evoked neuronal activity to connectivity using cross-correlation analysis of recordings from up to 150 neurons recorded simultaneously with high-density laminar electrode arrays.