Mechanisms of persistent neural activity

持续神经活动的机制

• 批准号: 10467871
• 负责人: Alexander C Huk
• 金额: $ 53.41万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10467871
• 关键词: Algorithms; Alzheimer' s Disease; Animals; Architecture; Area; Behavior; Behavioral Paradigm; Biological; Biological Models; Brain; Brain Diseases; Brain region; Calcium; Callithrix; Chronic; Code; Cognition; Complex; Computer Models; Data; Data Set; Development; Disease; Electrodes; Electrophysiology (science); Equilibrium; Exhibits; FarGo; Genetic; Health; Human; Image; Individual; Intelligence; Knowledge; Link; Macaca; Maintenance; Maps; Measurement; Measures; Memory; Modeling; Modernization; Motor; Motor Activity; Neurons; Neurophysiology - biologic function; Output; Parietal; Parietal Lobe; Parkinson Disease; Performance; Primates; Recurrence; Resolution; Rodent; Role; Saccades; Schizophrenia; Sensory; Short-Term Memory; Signal Transduction; Specificity; Statistical Data Interpretation; Statistical Models; Techniques; Testing; Thalamic structure; Time; Training; Visual; Work; cell type; clinically relevant; cognitive neuroscience; data-driven model; density; experimental study; extracellular; flexibility; foot; insight; large scale data; motor behavior; network models; neural circuit; neuronal circuitry; neurophysiology; nonhuman primate; novel; oculomotor; relating to nervous system; repaired; response; sensory input; theories; tool; two-photon

PROJECT SUMMARY / ABSTRACT Although many well-studied aspects of neural function involve activity driven by sensory inputs or occurring at the time of motor actions, the brain often links such fleeting sensory and motor signals with persistent activity. Somehow, neural circuits and individual neurons are capable of maintaining activity without additional input. This is a fundamental aspect of neural function and a critical building block of cognition. The mechanisms underlying persistent neural activity have long been considered in both experiment and theory, but there is little definitive mechanistic understanding of the circuit and cellular contributions to persistent activity. Indeed, theories of persistent activity are far more biologically nuanced than current empirical knowledge— especially in the nonhuman primate, from which our understanding should have greatest clinical relevance given the number of disorders that involve persistent activity. Here, we propose work that leverages advanced techniques for multiple scales (and specificities) of neural recordings with corresponding analyses of large- scale datasets to test detailed theories of how the brain generates and maintains persistent activity. Specific Aim 1. Establish the marmoset as a powerful complementary model system for dissecting persistent activity mechanisms in primate brains. We will demonstrate the viability of studying memory-guided saccades and persistent activity in the marmoset, using successful training approaches, electrophysiology, and calcium imaging to elicit the key behavior and to characterize the important brain areas in this exciting primate model system. Specific Aim 2. Characterize the large-scale circuitry underlying oculomotor persistent activity. Using large scale recordings of extracellular activity across multiple brain regions collecting during performance of a memory-guided saccade task, we will acquire a dataset of unprecedented scale to assess the large-scale circuitry underlying persistent activity. We will adapt, develop, and deploy advanced statistical models to capture the functional interactions between neurons and brain areas. Specific Aim 3. Test and refine theories of persistent activity with novel measurements at fine spatial and genetic resolution. We will perform both 2-photon imaging and high density electrophysiological measures of neural activity. The imaging will allow us to test the local circuit components of the theory, as well as to assess cell-type-specific contributions to persistent activity. High density electrophysiology will reveal the local circuit architecture and signal flow that are not accessible with coarser techniques. Integrated within our analysis framework, the resultant model of persistent activity will be supported and refined by multiple scales and forms of empirical evidence, all collected in the primate brain.

项目摘要/摘要 尽管神经功能的许多研究很好的方面涉及到由感觉输入驱动的活动或发生在 在运动动作的时间，大脑经常将这种fl发出的感觉和运动信号与持续的活动联系起来。 不知何故，神经回路和单个神经元能够在没有额外输入的情况下保持活动。 这是神经功能的一个基本方面，也是认知的关键组成部分。其作用机制 长期以来，实验和理论都认为潜在的持续性神经活动，但很少有 Defi对电路和细胞对持续活动的贡献的本能机制的理解。的确， 与当前的经验知识相比，持续活动的理论在生物学上要微妙得多--尤其是 在非人类灵长类动物中，我们的理解应该具有最大的临床意义，因为 涉及持续活动的疾病的数量。在这里，我们建议利用高级 多尺度(和特定fi城市)的神经记录技术及其相应的大样本分析 扩大数据集，测试大脑如何产生和维持持续活动的详细理论。 Speciific目标1.将绒猴建立为一个强大的补充解剖模型系统 灵长类动物大脑中的持续活动机制。 我们将展示研究记忆引导的眼跳和恒定活动在绒猴中的可行性， 使用成功的训练方法、电生理学和钙成像来引出关键行为，并 描述这个令人兴奋的灵长类动物模型系统中重要的大脑区域。 SPECIfic目标2.描述持续的动眼神经活动背后的大规模神经回路。 使用大规模记录跨多个脑区的细胞外活动在 记忆引导的扫视任务的性能，我们将获得一个前所未有的规模的数据集来评估 持续活动背后的大规模电路。我们将适应、发展和部署先进的统计 捕捉神经元和大脑区域之间功能相互作用的模型。 SPECIfic Aim 3.在fiNe空间用新的测量方法测试和重新验证持续活动的理论 和基因分辨率。 我们将对神经活动进行双光子成像和高密度电生理测量。这个 成像将使我们能够测试理论的本地电路组件，以及评估细胞类型-规格fic 对持之以恒的活动的贡献。高密度电生理学将揭示局部电路架构和 用较粗糙技术不能访问的信令fl。集成到我们的分析框架中， 持续性活动的结果模型将得到多个尺度和形式的经验性活动的支持和支持 证据都是在灵长类动物的大脑中收集的。