Directly measuring synaptic and population coupling in cortex during perception

直接测量感知过程中皮层的突触和群体耦合

• 批准号: 9893928
• 负责人: Bilal Haider
• 金额: $ 39.91万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9893928
• 关键词: Action Potentials; Address; Anesthesia procedures; Automobile Driving; Behavior; Behavioral; Biophysical Process; Brain; Cells; Cerebral cortex; Characteristics; Communication; Complex; Coupling; Dementia; Detection; Development; Disease; Epilepsy; Equilibrium; Exhibits; Goals; Impairment; Individual; Knowledge; Lead; Mammals; Measurement; Measures; Membrane Potentials; Modeling; Mus; Neurodevelopmental Disorder; Neurologic; Neurons; Outcome; Parvalbumins; Perception; Performance; Population; Positioning Attribute; Process; Research; Resolution; Rewards; Schizophrenia; Sensory; Sensory Process; Signal Detection Analysis; Signal Transduction; Silicon; Site; Stimulus; Structure; Synapses; Techniques; Validation; Visual; Visual Cortex; Visual Perception; Visuospatial; Withdrawal; Work; area striata; autism spectrum disorder; awake; density; effective therapy; excitatory neuron; experimental study; inhibitory neuron; innovation; nervous system disorder; neural network; optogenetics; patch clamp; response; spatiotemporal; theories; visual stimulus

Directly measuring synaptic and population coupling in cortex during perception The cerebral cortex is the defining brain structure of mammals and underlies our most complex sensory behaviors. A major need exists to identify how synaptic and network mechanisms in cortex lead to normal and impaired sensory perception and behavior. A prevailing model of cortical function postulates that synaptic excitation (E) and inhibition (I) exhibit a stable balance (E/I balance) that is disrupted during sensory impairments and neurodevelopmental diseases. Currently, there is no knowledge regarding synaptic E/I balance during sensory perception, nor its relationship to large-scale neural network activity. We are uniquely positioned to bridge this critical knowledge gap with an innovative combination of whole-cell patch-clamp and large-scale population recordings of defined excitatory and inhibitory neurons during visual perception in mice. This multi- scale approach will enable us to 1) Define how excitatory and inhibitory neuron populations spanning cortical layers predict the accuracy of visual perception 2) Reveal synaptic mechanisms that underlie visual perception 3) Define the relationship between excitatory and inhibitory population activity and synaptic mechanisms engaged by visual perception. SIGNIFICANCE. This project will meet a significant need to understand how excitatory and inhibitory activity in cortex is coordinated at the synaptic, network, and behavioral levels to support sensory perception. It is imperative to understand these processes in individual neurons, networks, and their synaptic inputs during behavior, so that we may better comprehend how to rectify sensory processing deficits characteristic of many neurological and neurodevelopmental disorders. INNOVATION. This project will provide innovative measurements and analysis of the relationship between single-neuron synaptic inputs and large-scale neural network activity during controlled perceptual behaviors. This combination of techniques will allow critical assessment of long-standing theories of cortical function (E/I balance) that require validation in relevant behavioral contexts. These results will provide conceptual innovation by detailing how inhibition sculpts and coordinates excitatory activity in cortex to orchestrate perceptual behaviors.

感知过程中皮层突触和群体耦合的直接测量 大脑皮层是哺乳动物大脑的主要结构，也是我们最复杂的感觉器官的基础。 行为。主要需要确定皮层中的突触和网络机制如何导致正常和 感官知觉和行为受损。一个流行的皮质功能模型假设， 兴奋（E）和抑制（I）表现出稳定的平衡（E/I平衡），在感觉障碍期间被破坏 和神经发育疾病。目前，还没有关于突触E/I平衡的知识， 感官知觉，也不是它与大规模神经网络活动的关系。我们有独特的优势， 弥合这一关键的知识差距与创新的组合全细胞膜片钳和大规模 在小鼠的视觉感知过程中确定的兴奋性和抑制性神经元的群体记录。这多- 规模的方法将使我们能够1）定义兴奋性和抑制性神经元群体如何跨越皮层 层预测视觉感知的准确性2）揭示视觉感知的突触机制 3)定义兴奋和抑制群体活动与突触机制之间的关系 被视觉感知所吸引。 意义这个项目将满足一个重要的需要，了解如何兴奋和抑制活动， 皮质在突触、网络和行为水平上协调以支持感官知觉。是 必须了解这些过程中的个别神经元，网络和他们的突触输入， 行为，以便我们可以更好地理解如何纠正感觉处理缺陷的特点，许多 神经和神经发育障碍。 创新该项目将提供创新的测量和分析之间的关系， 单神经元突触输入和大规模神经网络活动在受控的感知行为。 这种技术的结合将允许对长期存在的皮质功能（E/I）理论进行批判性评估 平衡），需要在相关的行为背景下进行验证。这些结果将提供概念创新 通过详细描述抑制如何塑造和协调皮层的兴奋性活动， 行为。