Cortical Synaptic Circuitry Underlying Visual Processing

项目摘要 皮层神经元处理感觉信息的方式由其功能性突触输入决定 巡回赛。该电路包含三个要素：1)兴奋性和抑制性的输入连接 突触前神经元；2)每个输入的强度和动态特性；3)加工特性 每个突触前神经元。尽管对这些元素中的每一个进行单独解密有助于提取 兴奋性和抑制性输入如何相互作用以产生神经元的输出响应特性，以及 在一个完整的系统中解决所有这些组件的完整研究是必要的，但仍是一个 巨大的挑战。活体全细胞电压钳记录提供了一种独特而有价值的 直接分离和揭示功能性兴奋性突触和抑制性突触的方法 在特定感官刺激下的输入。因为激发和抑制的时空属性是 由上述电路元件确定，它提供了一种弥合连接之间差距的方法 有功能的。在这个项目中，我们将继续利用这种方法的力量来理解 多种视觉处理功能，并将其应用扩展到唤醒小鼠初级视皮层 (V1)。首先，我们将确定抑制和激发之间的调谐关系 不同皮层兴奋性神经元的定向选择性和空间感受野。vbl.使用 神经元模型和动态钳制记录，我们将研究抑制在 塑造功能选择性。接下来，基于我们最近发现的一个有趣的相关性 运动刺激下兴奋性反应的方向调谐与空间不对称性的关系 由平稳刺激引起的兴奋性输入强度，我们将研究方向选择性如何 通过测试一种新的假设，即空间不对称性可以是 在相反方向的刺激下转换为差分时间求和。通过光遗传 大脑皮质兴奋性神经元放电的沉默，这种空间不对称性的起源也将被检查。 最后，通过光遗传学辅助细胞鉴定，我们将应用全细胞电压钳 记录到PV抑制神经元，并确定其普遍较弱的选择性的机制。 总之，拟议的实验将产生重要的新见解，了解大脑皮质如何发挥功能 突触回路的组织，以及大脑皮质处理和感觉知觉如何在 导致兴奋-抑制平衡被打乱的神经系统疾病。

Project Summary The way a cortical neuron processes sensory information is determined by its functional synaptic input circuit. This circuit contains three elements: 1) input connectivity from excitatory and inhibitory presynaptic neurons; 2) the strength and dynamic properties of each input; 3) processing properties of each presynaptic neuron. Although separate deciphering of each of these elements helps to extract how excitatory and inhibitory inputs interact to generate of output response properties of the neuron, an integral study addressing all these components in an intact system is necessary but remains to be a tremendous challenge. In vivo whole-cell voltage-clamp recording provides a unique and valuable approach for us to directly isolate and reveal the summed functional excitatory and inhibitory synaptic inputs under specific sensory stimuli. As the spatiotemporal properties of excitation and inhibition are determined by the above circuit elements, it provides a means to bridging the gap between connectivity with function. In this project, we will continue to harness the strength of this approach to understand various visual processing functions, and extend its application to awake mouse primary visual cortex (V1). First, we will determine the tuning relationship between inhibition and excitation underling orientation selectivity and spatial receptive fields in excitatory neurons in different cortical layers. Using neuron modeling and dynamic clamp recording, we will examine the diverse roles of inhibition in shaping functional selectivity. Next, based on our recent discovery of an interesting correlation between the direction tuning of excitatory responses under moving stimuli and the spatial asymmetry of excitatory input strengths evoked by stationary stimuli, we will examine how direction selectivity can be generated de novo in the cortex by testing a novel hypothesis that the spatial asymmetry can be converted into differential temporal summation under stimuli of opposite directions. By optogenetic silencing of cortical excitatory neuron spiking, the origin of this spatial asymmetry will also be examined. Finally, through optogenetics assisted cell identification, we will apply the whole-cell voltage-clamp recording to PV inhibitory neurons, and determine the mechanisms for their generally weak selectivity. Together, the proposed experiments will generate important new insights into how functional cortical synaptic circuits are organized and how cortical processing and sensory perception may go awry under neurological disease conditions which result in disrupted excitation-inhibition balance.