Cortical Synaptic Circuitry Underlying Visual Processing

视觉处理下的皮质突触回路

• 批准号: 9916763
• 负责人: Huizhong Whit Tao
• 金额: $ 47.39万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9916763
• 关键词: Address; Anesthesia procedures; Axon; Cells; Closure by clamp; Coupling; Elements; Equilibrium; Exhibits; Generations; Individual; Lead; Mental disorders; Methods; Modeling; Mus; Neurons; Output; Parvalbumins; Pathology; Perception; Physiology; Preparation; Property; Role; Sensory; Sensory Process; Shapes; Signal Transduction; Somatostatin; Spatial Distribution; Stimulus; Sum; Synapses; System; Techniques; Testing; Thalamic structure; Visual Cortex; Wakefulness; area striata; awake; base; combinatorial; excitatory neuron; experimental study; in vivo; inhibitory neuron; innovation; insight; nervous system disorder; neural circuit; novel; optogenetics; orientation selectivity; preservation; presynaptic neurons; receptive field; response; sensory stimulus; spatiotemporal; synaptic inhibition; visual processing; visual receptive field; voltage clamp

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.

项目摘要 皮层神经元处理感觉信息的方式是由其功能性突触输入决定的 电路.这个回路包含三个要素：1）兴奋性和抑制性的输入连通性 突触前神经元; 2）每个输入的强度和动态特性; 3） 每个突触前神经元虽然单独破译这些元素有助于提取 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， 在一个完整的系统中处理所有这些组成部分的综合研究是必要的， 巨大的挑战在体内全细胞电压钳记录提供了一个独特的和有价值的 一种直接分离和揭示兴奋性和抑制性突触的方法， 特定感官刺激下的输入。由于兴奋和抑制的时空特性是 由上述电路元件决定，它提供了一种方法来桥接连接之间的差距 功能。在这个项目中，我们将继续利用这种方法的优势来了解 各种视觉处理功能，并将其应用扩展到清醒小鼠初级视皮层 （V1）。首先，我们将确定抑制和兴奋之间的调谐关系 不同皮层层兴奋性神经元的方向选择性和空间感受野。使用 神经元建模和动态钳记录，我们将研究抑制的不同作用， 形成功能选择性。接下来，基于我们最近发现的一个有趣的相关性， 在运动刺激下兴奋性反应的方向调谐和空间不对称性之间， 兴奋性输入强度引起的静态刺激，我们将研究如何方向选择性可以 通过测试一个新的假设，即空间不对称性可以在大脑皮层中重新产生， 在相反方向的刺激下转换成微分时间总和。通过光遗传学 通过观察皮质兴奋性神经元尖峰的沉默，还将检查这种空间不对称性的起源。 最后，通过光遗传学辅助细胞鉴定，应用全细胞电压钳技术 记录PV抑制神经元，并确定其一般弱选择性的机制。 总之，拟议中的实验将产生重要的新见解，了解功能性皮层 突触电路的组织和皮层处理和感官知觉如何可能出错， 导致兴奋-抑制平衡被破坏的神经疾病状况。