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

项目摘要/摘要 系统神经科学认为脑干去甲肾上腺素能核蓝斑(LC)是 全球唤醒信号的来源，它通过改变整个过程中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有1600英镑的小收藏来实现的 啮齿类动物的神经元同步放电。然而，最近，许多人的首次大规模录音 麻醉大鼠LC单个单位同时显示LC群活性包括 一种独立活跃的不同群体的细微差别模式。同时，化学发生和 对行为啮齿类动物LC的光遗传学操作表明，LC包含 为特定认知功能提供前脑回路特定神经调节的神经元。这些 最近的进步迫使该领域记录了行为动物的LC合奏。然而，这需要 克服迄今LC有限的行为动物脑干运动障碍 录制到多个单元的活动或单个单元。在这里，我们将建立超灵活的可行性 用于长达数月的LC系综的多电极探头，称为“纳米电子线”(Net) 未麻醉大鼠的录音。作为一项展示NETS可行性的概念验证研究， 我们在自由活动的大鼠的视皮层中同时记录了大约150个单一单位，最多记录了4个 月份。在本项目中，我们的目标是在头部固定行为大鼠的LC中植入512个电极，并 同时记录100个LC单个单位，以及正在进行的觉醒/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，这个项目将是LC研究的变革性。我们的方法将广泛用于 神经学家记录在其他脑干和皮质下结构中，其中记录了许多单个 单位是很难的。我们的总体目标是使用此R34来建立该方法，这将使 随后提交的有针对性的大脑回路项目R01集中在LC整体活动的作用上 在认知僵化的电路基础上，这是由长达数月的慢性压力所沉淀的。

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.