Mechanisms of stimulus-induced network focusing

项目摘要 大规模的记录发现，感觉、认知和运动网络中的单个神经元经常 即使在输入相同的情况下，也要参与。这种变化的原因尚不清楚， 这是该领域辩论的一个活跃话题。它反映了神经元参与的随机性，还是一种适应性的 在健康的大脑功能中起着重要作用的特征？这种应用的科学前提是 后一种--参与神经元反应了许多神经元固有的“聚焦”机制的运作 网络，使他们能够快速灵活地重新安排哪些神经元被调用来处理特定的 信息在当下的背景下。 这一假设出乎意料地出现在我们的大规模记录的节奏性逃避游泳网络， 海洋软体动物Tritonia diomedea。我们惊讶地发现，在最初的几秒钟， 对一个意想不到的令人厌恶的感觉输入做出反应，Tritonia的游泳运动程序迅速调整自己， 许多最初沉默的神经元进入爆发的群体，并将其他神经元驱逐出去，显然是为了 逃跑在Tritonia的情况下，“聚焦”状态保持几分钟， 更快启动的运动程序应该同样的刺激重现。许多脊椎动物的研究都报告说， 随着重复刺激，响应网络的规模不断增长，但这种机制和目的并不明确。 现象知之甚少。 该项目的目标是揭示潜在的机制，这可能是一个重要的多功能性过程， 许多大脑网络中的健康功能-一个允许他们快速重新分配神经元以适应特定的 上下文，然后保持这种专注状态持续一段时间。该项目有两个具体目标： 1将映射重新分配的神经元，并解决几个问题，关于这种现象， 了解网络聚焦过程。目的2将确定驱动快速再分化的细胞机制。 神经元的分配进入和退出的爆裂逃逸游泳网络，因为它的重点。快速的原则 这里研究的网络聚焦可能会促进治疗或预防 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.