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 以不同的方式参与，即使在提供相同输入的情况下也是如此。造成这种差异的原因尚不清楚，而且 这是该领域的一个活跃的辩论话题。它是反映了神经元参与的随机性，还是适应性？ 对健康的大脑功能起重要作用的功能？这个应用程序的科学前提是 后者--可变参与神经元反映了许多神经元与生俱来的“聚焦”机制的运作 网络，允许他们快速灵活地重新安排哪些神经元被调用来处理特定的 在当前的背景下的信息。 这一假设出乎意料地出现在我们对有节奏的逃逸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，在最初几秒钟内 作为对意想不到的厌恶感官输入的反应，Tritonia的游泳运动程序迅速调整自己，拉动 许多最初沉默的神经元进入激增的种群，并将其他神经元赶走，显然是为了 逃走。在这种Tritonia情况下，然后保持几分钟的“聚焦”状态，从而实现更强的， 起效更快的运动计划应该会重现同样的刺激。许多对脊椎动物的研究报告说， 在重复刺激下的反应网络规模的增长，但这样做的机制和目的 人们对这些现象知之甚少。 该项目的目标是揭示可能是一个重要的多功能性过程的潜在机制 许多大脑网络中的健康功能-允许它们快速重新分配神经元以适应特定的 上下文，然后在持续的一段时间内保持该聚焦状态。该项目有两个具体目标：目标 1将绘制重新分配神经元的图，并解决与这种不良现象相关的几个问题 了解网络聚焦流程。目标2将确定驱动快速恢复的细胞机制 当它集中注意力时，神经元进入和离开爆裂的逃逸游泳网络。快速性原则 将在这里重点研究的网络可能会促进治疗或防止心脏功能下降的新方法 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.