Capturing large-scale locus coeruleus single neuron activity in behaving rats with nanoelectronic threads (NETs), an ultra-flexible multi-electrode probe

项目概要/摘要 系统神经科学将脑干去甲肾上腺素核、蓝斑 (LC) 视为 全局唤醒信号的来源，通过改变整个过程的操作来调节认知功能 整个中枢神经系统。这大概是通过这个仅约 1,600 个的小收藏来实现的 啮齿动物的神经元同步放电。然而最近，许多人的第一次大规模录音 在麻醉大鼠中同时进行 LC 单个单位证明 LC 群体活性包括 独立活动的不同整体的微妙模式。同时，化学遗传学和 对行为啮齿动物的 LC 进行光遗传学操作表明，LC 包含以下子集： 提供特定认知功能的前脑回路特定神经调节的神经元。这些 最近的进展迫使该领域记录行为动物的 LC 系综。然而，这需要 克服行为动物脑干运动的障碍，迄今为止限制了LC 记录多单元活动或单个单元。在这里，我们将建立超灵活的可行性 多电极探针，称为“纳米电子线”(NET)，用于长达数月的 LC 整体 未麻醉大鼠的录音。作为证明 NET 可行性的概念验证研究， 我们在自由移动的老鼠的视觉皮层中同时记录了约 150 个单位，持续时间长达 4 次。 几个月。在这个项目中，我们的目标是在头部固定行为大鼠的 LC 中植入 512 个电极， 同时记录 100 个 LC 单个单元，以及持续的唤醒/行为状态（瞳孔大小、 运动、口面部运动等）。通过增加订单记录的单位数量 规模上，该项目将对液晶研究产生变革。我们的方法将广泛用于 神经科学家在其他脑干和皮层下结构中进行记录，其中记录了许多单个 单位很难。我们的总体目标是使用这个 R34 来建立该方法，这将使得 随后提交的目标脑回路项目 R01 重点关注 LC 系综活动的作用 认知僵化的循环基础是由长期的、长达数月的压力引发的。

Project Summary / Abstract Systems neuroscience has viewed the brainstem noradrenergic nucleus, Locus Coeruleus (LC), as the source of a global arousal signal, which modulates cognitive functions by altering operations throughout the entire central nervous system. This is achieved, presumably, by this small collection of only ~1,600 neurons in rodents spiking synchronously. Recently, however, the first large-scale recordings of many LC single units simultaneously in anesthetized rats demonstrated that LC population activity consists of a nuanced pattern of distinct ensembles that are independently active. In parallel, chemogenetic and optogenetic manipulations of the LC in behaving rodents revealed that the LC contains subsets of neurons that provide forebrain circuit-specific neuromodulation of specific cognitive functions. These recent advances compel the field to record LC ensembles in behaving animals. However, this requires surmounting the obstacle of brainstem movement in behaving animals which has heretofore limited LC recordings to multi-unit activity or one single unit. Here, we will establish the feasibility of ultra-flexible multi-electrode probes, called ‘nanoelectronic threads’ (NETs), for months-long LC ensemble recordings in unanesthetized rats. As a proof-of-concept study demonstrating the feasibility of NETs, we recorded ~150 single units simultaneously in the visual cortex of freely moving rats for up to four months. In this project, we aim to implant 512 electrodes in the LC of the head-fixed behaving rat and record 100s of LC single units simultaneously, along with ongoing arousal/behavioral state (pupil size, locomotion, orofacial movements, etc.). By increasing the number of units recorded by orders of magnitude, this project will be transformational for LC research. Our approach will be broadly useful to neuroscientists recording in other brainstem and subcortical structures in which recording many single units is difficult. Our overall goal is to use this R34 to establish the method, which will enable a subsequent Targeted Brain Circuits Project R01 submission focused on the role of LC ensemble activity in the circuit basis of cognitive rigidity that is precipitated by chronic, months-long stress.