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 系统神经科学认为脑干去甲肾上腺素能核，蓝斑（LC），作为 一个全局唤醒信号的来源，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。据推测，这是通过仅约1，600个的小集合实现的。 啮齿类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，LC单个单位同时显示LC群体活性包括： 一种由独立活动的不同群体组成的微妙模式。同时，化学遗传和 在行为啮齿类动物中对LC的光遗传学操作揭示了LC含有以下亚群： 提供特定认知功能的前脑回路特异性神经调节的神经元。这些 最近的进展迫使该领域在行为动物中记录LC集合。但这需要 克服了迄今限制LC的行为动物脑干运动障碍 记录到多单元活动或一个单一的单位。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合奏 记录在未麻醉的大鼠。作为一项概念验证研究，展示了NET的可行性， 我们在自由活动的大鼠的视觉皮层中同时记录了大约150个单位， 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， 沿着记录100个LC单个单位，以及正在进行的唤醒/行为状态（瞳孔大小， 运动、口面运动等）。通过增加记录的单位数量， 规模，这个项目将是转型LC研究。我们的方法将广泛适用于 神经科学家在其他脑干和皮层下结构中记录了许多单个的 单位很难。我们的总体目标是使用这个R34来建立方法，这将使 随后提交的靶向脑回路项目R 01关注LC整体活动的作用 在认知僵化的电路基础上，这是由慢性，长达数月的压力沉淀。

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.