Mechanisms of stimulus-induced network focusing

刺激引起的网络聚焦机制

• 批准号: 10185840
• 负责人: William Frost
• 金额: $ 39万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10185840
• 关键词: Address; Affect; Aging; Automobile Driving; Brain; Cognitive; Data; Disease; Effectiveness; Electrophysiology (science); Elements; Fire - disasters; Goals; Health; Human; Image; Impaired cognition; Individual; Maps; Motor; Neurons; Periodicity; Play; Population; Process; Property; Reporting; Role; Sensory; Stimulus; Swimming; System; Time; Vertebrates; Work; cognitive function; flexibility; insight; neural network; novel strategies; operation; phenomenological models; prevent; programs; rapid growth; sensory input; voltage sensitive dye

Project Summary Large-scale recordings are discovering that individual neurons in sensory, cognitive, and motor networks often participate variably, even when presented with identical inputs. The reason for such variability is unclear, and an active topic of debate in the field. Does it reflect randomness in neuronal participation, or is it an adaptive feature that plays an essential role in healthy brain function? The scientific premise of this application is the latter—that variably participating neurons reflect the operation of a “focusing” mechanism innate to many networks that allows them to rapidly and flexibly rearrange which neurons are called upon to process specific information in the context of the moment. This hypothesis emerged unexpectedly from our large-scale recordings of the rhythmic escape swim network of the marine mollusk Tritonia diomedea. We were surprised to discover that during the initial seconds of responding to an unexpected aversive sensory input, Tritonia's swim motor program rapidly tunes itself, pulling many initially-silent neurons into the bursting population and driving others out, apparently optimizing itself for escape. In this Tritonia case, the “focused” state is then maintained for several minutes, enabling a stronger, faster-onset motor program should the same stimulus recur. Many studies in vertebrates have reported rapid growth in the size of responding networks with repeated stimulation, but the mechanisms and purpose of such phenomena are poorly understood. This project's goal is to uncover the mechanisms underlying what may be an important versatility process for healthy function in many brain networks—one that allows them to rapidly re-allocate neurons to suit a specific context, and then hold that focused state for a sustained period of time. The project has 2 Specific Aims: Aim 1 will map the re-allocating neurons and address several issues regarding the phenomenology of this poorly understood network focusing process. Aim 2 will determine the cellular mechanisms driving the rapid re- allocation of neurons into and out of the bursting escape swim network as it focuses. The principles of rapid network focusing to be investigated here may promote novel approaches for treating or preventing declines in cognitive function in aging and disease.

项目摘要 大规模录音发现，经常有感觉，认知和运动网络中的个体神经元 特别是，即使出现相同的输入。这种可变性的原因尚不清楚，并且 该领域的积极辩论主题。它是否反映了神经元参与的随机性，还是适应性的 功能在健康大脑功能中起着至关重要的作用？该应用程序的科学前提是 后者 - 大量参与的神经元反映了许多与众不同的“聚焦”机制的操作 使他们可以快速，灵活地重新排列哪些神经元的网络来处理特定的网络 在当下的上下文中的信息。 这个假设出乎意料地来自我们关于有节奏的逃生游泳网络的大规模录音 海洋软体动物Tritonia Diomedea。我们惊讶地发现，在最初的几秒钟 Tritonia的游泳运动计划响应意外的厌恶感官输入，迅速调整 许多最初有丝毫有利的神经元进入爆发的人群并将其他人赶出，显然为自己优化 逃脱。在此Tritonia案件中，然后将“重点”状态保持几分钟，使一个更强大的状态使得 更快发出的电动机计划应相同的刺激复发。许多脊椎动物的研究都报道了 反复刺激的响应网络规模的增长，但这种机制和目的 现象知之甚少。 该项目的目标是揭示可能是重要的多功能性过程的机制 在许多大脑网络中的健康功能 - 一个使它们能够快速重新分配神经元以适合特定的神经元 背景，然后在持续的一段时间内保持这种重点状态。该项目有2个特定目标：目标 1将映射重新分配神经元，并解决有关这种差的现象学的几个问题 了解网络聚焦过程。 AIM 2将确定驱动快速重复的细胞机制 当神经元聚焦时，神经元进入爆发的逃生游泳网络。快速原则 在这里要调查的网络聚焦可能会促进治疗或防止下降的新方法 衰老和疾病的认知功能。