Large-scale monitoring of circuits for adaptation and novelty detection in primary visual cortex

初级视觉皮层适应和新颖性检测电路的大规模监测

• 批准号: 10300007
• 负责人: Jordan Marie Ross
• 金额: $ 7.14万
• 依托单位: GEORGIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2023-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10300007
• 关键词: 3-Dimensional; Address; Anatomy; Appearance; BRAIN initiative; Behavior; Biological; Calcium; Cells; Code; Color; Communities; Complex; Computer Models; Conscious; Cortical Column; Coupling; Data; Detection; Environment; Exhibits; Feedback; Formulation; Fright; Future; Goals; Image; Interneurons; Intervention; Learning; Mediating; Modality; Modeling; Monitor; Neocortex; Nervous System Physiology; Neural Network Simulation; Neurons; Organism; Output; Pattern; Perception; Photons; Play; Population; Process; Publishing; Pyramidal Cells; Role; Sensory; Smell Perception; Stimulus; Testing; Training; Vasoactive Intestinal Peptide; Vision; Visual; area striata; artificial neural network; base; behavior test; career; cell type; deviant; excitatory neuron; experience; experimental study; flexibility; insight; lens; neocortical; network models; neural circuit; neuropsychiatric disorder; neurotechnology; novel; optogenetics; relating to nervous system; response; sensory mechanism; sensory stimulus; success; theories; tool; two-photon

Project Summary/Abstract In a world filled with sensory information, the ability to filter out repetitive or redundant stimuli while still maintaining the ability to detect change in the environment is critical to biological success. Studies have characterized reduced cortical responses to repetitive stimuli (adaptation) and augmented cortical responses to stimuli that differ from these expected regularities (novelty detection); however, the cortical circuits that enable flexibly encoding stimuli based on the context in which they are experienced remain unknown. Disinhibitory microcircuits, especially those mediated by vasoactive intestinal polypeptide-expressing inhibitory interneurons (VIPs), may play a role in this flexible coding by altering the inhibition supplied to principal excitatory neurons (PYRs) in neocortex. Despite this, the relationship between neural activity of VIPs and PYRs during adaptation and novelty detection remain poorly understood. In this proposal, I seek to use fast dual-color, three-dimensional, two-photon calcium imaging to simultaneously monitor neural activity of both VIPs and PYRs in primary visual cortex during a classic visual “oddball” paradigm (Aim 1). This paradigm presents the same stimulus in control, repetitive, and rare/deviant contexts, which enables directly recording neural responses to the same stimulus when it is an established regularity and when it is novel and thus deviates from established regularity. I will then use data and theory analysis tools to computationally model neocortical adaptation and novelty detection (Aim 2) by incorporating anatomical and neural recording data from PYRs and interneuron populations (including VIPs), which are often excluded from network models. The creation of this holistic model is likely to reveal fundamental circuitry that gives rise to flexible neural encoding of sensory stimuli. Finally, I will integrate optogenetic interventional tools for circuit manipulation with two-photon imaging to directly test the relationship between VIP neural activity and adaptation and novelty detection in PYRs. Altogether, these aims directly address several of the BRAIN Initiative 2025 high priority goals: monitor neural activity, interventional tools, data and theory analysis, and integrated approaches. Furthermore, the experiments proposed under these aims will result in significant technical and theoretical training for the applicant and will advance essential understanding of how excitatory, inhibitory, and disinhibitory circuits across cortical layers diverge in their dynamic neural activity and differentially contribute to sensory processing.

项目摘要/摘要 在一个充满感官信息的世界中 保持检测环境变化的能力对于生物学成功至关重要。研究有 表征对重复刺激的皮质反应减少（适应）和对皮质的增强反应 刺激与这些预期的规律性不同（新颖性检测）；但是，启用的皮质电路 基于它们所经历的上下文灵活地编码刺激仍然未知。抑制性 微电路，尤其是由血管活性肠道多肽表达抑制性神经元介导的 （VIP），可以通过改变提供给主兴奋性神经元的抑制作用来在此灵活的编码中发挥作用 （Pyrs）在新皮层中。尽管如此，适应过程中VIP和PYR的神经活动之间的关系 新颖的检测仍然鲜为人知。 在此提案中，我寻求使用快速的双色，三维两光子钙成像 类似地监测经典视觉的初级视觉皮层中VIP和PYR的神经元活性 “ ODBALL”范式（AIM 1）。该范式在对照，重复和稀有/偏差中表现出相同的刺激 上下文，可以直接记录对同一刺激的神经反应 规律性及其新颖时，因此偏离了既定的规律性。然后，我将使用数据和理论 分析工具通过合并来模拟新皮质适应和新颖性检测（AIM 2） 来自Pyrs和Interneuron群体（包括VIP）的解剖学和神经记录数据通常是 从网络模型中排除。这种整体模型的创建可能揭示了基本电路 引起感觉刺激的柔性神经编码。最后，我将整合光遗传学的干预工具 用于使用两光子成像的电路操作，直接测试VIP神经活动与 Pyrs中的适应性和新颖性检测。这些目的总共直接解决了大脑倡议的几个 2025高优先级目标：监视神经活动，介入工具，数据和理论分析，并集成 方法。此外，根据这些目标提出的实验将导致大量的技术和 对申请人的理论培训，并将提高对规范，抑制性和 跨皮质层的抑制电路在其动态神经活动中发散，并有所不同 感官处理。