Mechanisms of stimulus-induced network focusing

项目概要 大规模记录发现，感觉、认知和运动网络中的单个神经元经常 即使提供相同的输入，也会以不同的方式参与。造成这种变化的原因尚不清楚，并且 该领域争论的一个活跃话题。它是否反映了神经元参与的随机性，或者它是一种适应性 对健康的大脑功能起着重要作用的功能？该应用的科学前提是 后者——不同参与的神经元反映了许多人与生俱来的“聚焦”机制的运作 网络使它们能够快速灵活地重新排列哪些神经元被要求处理特定的 当下上下文中的信息。 这个假设出人意料地出现在我们对有节奏的逃生游泳网络的大规模记录中。 海洋软体动物 Tritonia diomedea。我们惊讶地发现，在最初的几秒钟内 为了应对意外的厌恶性感官输入，Tritonia 的游泳运动程序会快速自我调整，拉动 许多最初沉默的神经元进入激增的群体并驱逐其他神经元，显然是为了优化自身 逃脱。在这个 Tritonia 案例中，“专注”状态会维持几分钟，从而实现更强大、 如果重复出现相同的刺激，则运动程序会启动得更快。许多脊椎动物研究报告称， 随着重复刺激，反应网络的规模会增长，但这种机制和目的 人们对现象知之甚少。 该项目的目标是揭示潜在的重要多功能过程的机制 许多大脑网络的健康功能——使它们能够快速重新分配神经元以适应特定的需求 背景，然后持续保持一段时间的专注状态。该项目有 2 个具体目标： 1 将绘制重新分配神经元的图，并解决有关这种不良现象的几个问题 了解网络聚焦过程。目标 2 将确定驱动快速修复的细胞机制 当突发逃逸游泳网络聚焦时，将神经元分配进出。快速原则 这里重点研究的网络可能会促进治疗或预防疾病衰退的新方法 衰老和疾病中的认知功能。

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.