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

项目摘要/摘要 在一个充满感官信息的世界里，过滤掉重复或多余的刺激的能力 保持检测环境变化的能力对生物学上的成功至关重要。研究表明， 表现为对重复刺激的皮质反应减弱(适应)和增强的皮质反应 不同于这些预期规则的刺激(新颖性检测)；然而，使 基于刺激经历的上下文对刺激进行灵活编码仍然是未知的。去抑制 微回路，尤其是由血管活性肠多肽表达的抑制性中间神经元介导的微回路 (VIPS)可能通过改变供应给主要兴奋性神经元的抑制而在这种灵活的编码中发挥作用 (PYRs)在新皮质。尽管如此，在适应过程中VIP和PYRs的神经活动之间的关系 新颖性检测仍然知之甚少。 在这项提议中，我寻求使用快速双色、三维、双光子钙成像来 同时监测经典视觉中初级视皮层VIPs和PYRs的神经活动 “古怪”范式(目标1)。这种范式在控制、重复和罕见/异常方面呈现出相同的刺激 上下文，这使得能够直接记录当它被建立时对相同刺激的神经反应 规律性，当它是新奇的，从而偏离既定的规律性。然后我将使用数据和理论 用于对新皮质适应和新颖性检测进行计算建模的分析工具(目标2) 来自PYR和中间神经元群体(包括VIP)的解剖和神经记录数据，这通常是 从网络模型中排除。这种整体模型的创建很可能揭示出 产生了对感觉刺激的灵活神经编码。最后，我将整合光遗传干预工具 用于双光子成像的电路操作，以直接测试VIP神经活动与 PYRs中的适应和新颖性检测。总之，这些目标直接解决了大脑倡议的几个问题 2025年优先目标：监测神经活动、介入工具、数据和理论分析以及综合 接近了。此外，在这些目标下提出的实验将产生重大的技术和 为申请者提供理论培训，并将促进对兴奋性、抑制性和 跨皮质各层的去抑制回路在其动态神经活动上存在差异，并在不同程度上对 感官处理。

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.