Cortical synaptic circuitry underlying visual processing

视觉处理的皮层突触电路

• 批准号: 8690848
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8690848
• 关键词: Accounting; Address; Cells; Development; Equilibrium; Exhibits; Generations; Image; Individual; Label; Lead; Mental disorders; Methods; Modeling; Molecular Genetics; Motion Perception; Mus; Neurons; Optics; Parvalbumins; Pathology; Pattern; Perception; Physiology; Property; Relative (related person); Role; Sensory Process; Shapes; Signal Transduction; Source; Stimulus; Structure; Subgroup; Synapses; Techniques; Testing; Thalamic structure; Transgenic Mice; Visual Cortex; base; cell type; excitatory neuron; in vivo; information processing; inhibitory neuron; innovation; insight; mouse model; nervous system disorder; neural circuit; optogenetics; orientation selectivity; presynaptic; receptive field; relating to nervous system; research study; response; spatiotemporal; tool; two-photon; visual process; visual processing; visual stimulus; voltage clamp

DESCRIPTION (provided by applicant): The cortical processing of sensory information depends critically on the orchestrated activity of interconnected excitatory and inhibitory neurons. Understanding the structure of these excitatory and inhibitory synaptic circuits is key for comprehending how information processing is achieved in the cortex, but the progress has been limited previously by technical difficulties in bridging connectivity and function. The recent development of molecular and genetic tools in the mouse makes it an attractive model for systematically dissecting synaptic circuitry underlying cortical functions. Taking advantage of these tools, we will be able to integrate multiple approaches to address synaptic circuitry mechanisms for the fundamental receptive field properties of mouse primary visual cortical neurons. In this project, we will first reveal the spatiotemporal interplays of visually evoked excitatory and inhibitory synaptic inputs to excitatory neurons with in vivo whole-cell voltage-clamp recordings. Specifically, we will determine the synaptic mechanisms underlying two fundamental visual processing properties of cortical excitatory neurons, the directional selectivity and the contrast invariance of orientation selectivity. We will then dissect the functional contribution of excitatory inputs from different origins with optogenetic methods. By silencing the cortex with optogenetic activation of a specific group of inhibitory neurons, we will determine the respective contribution of thalamocortical and intracortical input to orientation selectivity of layer 4 excitatory neurons. Finally, by developing two-photon imaging guided whole-cell voltage-clamp recording techniques in transgenic mouse models, we will determine the synaptic mechanisms for the weak orientation tuning exhibited by pavalbumin-positive cortical inhibitory neurons. These proposed studies will potentially provide 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.

描述（由申请人提供）：感觉信息的皮层处理关键取决于相互关联的兴奋性和抑制性神经元的协调活动。了解这些兴奋性和抑制性突触回路的结构是理解皮层如何实现信息处理的关键，但之前的进展因桥接连接和功能方面的技术困难而受到限制。最近的 小鼠分子和遗传工具的发展使其成为系统剖析皮层功能下突触回路的有吸引力的模型。利用这些工具，我们将能够整合多种方法来解决小鼠初级视觉皮层神经元基本感受野特性的突触电路机制。在这个项目中，我们将首先通过体内全细胞电压钳记录揭示视觉诱发的兴奋性和抑制性突触输入对兴奋性神经元的时空相互作用。具体来说，我们将确定皮层兴奋性神经元的两个基本视觉处理特性（方向选择性和方向选择性的对比度不变性）背后的突触机制。然后，我们将用光遗传学方法剖析不同来源的兴奋性输入的功能贡献。通过光遗传学激活一组特定的抑制性神经元来沉默皮质，我们将 确定丘脑皮质和皮质内输入对第 4 层兴奋性神经元方向选择性的各自贡献。最后，通过在转基因小鼠模型中开发双光子成像引导的全细胞电压钳记录技术，我们将确定新蛋白阳性皮质抑制神经元表现出的弱定向调节的突触机制。这些拟议的研究可能会为功能性皮层突触回路如何组织以及皮层处理和感觉知觉如何在神经系统疾病条件下出错从而导致兴奋抑制平衡破坏提供重要的新见解。