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

使用超灵活的多电极探针纳米电子线 (NET) 捕获行为大鼠的大规模蓝斑单神经元活动

• 批准号: 10300345
• 负责人: Nelson Totah
• 金额: $ 42.29万
• 依托单位: UNIVERSITY OF HELSINKI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10300345
• 关键词: Address; Affect; Anesthesia procedures; Animals; Area; Arousal; Attention; Behavior; Behavioral; Brain; Brain Stem; Cell Nucleus; Cells; Chronic; Chronic stress; Cognitive; Collection; Electrodes; Etiology; Event; Future; Goals; Head; Impaired cognition; Impairment; Implant; Locomotion; Measures; Mental disorders; Methods; Movement; Neuraxis; Neurons; Neurosciences; Neurotransmitters; Norepinephrine; Operative Surgical Procedures; Outcome; Pattern; Population; Prefrontal Cortex; Prosencephalon; Pupil; Rattus; Research; Risk Factors; Rodent; Role; Running; Signal Transduction; Sleep; Sleep disturbances; Source; Stress; Structure; Symptoms; System; Task Performances; Technology; Testing; Time; Visual Cortex; Work; biological adaptation to stress; cognitive function; cognitive rigidity; cognitive task; design; flexibility; implantable device; innovation; locus ceruleus structure; nanoelectronics; neuroregulation; new technology; noradrenergic; operation; optogenetics; orofacial; prevent; psychiatric symptom; response; success; tool; treadmill

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.

项目摘要 /摘要 系统神经科学已将脑干去肾上腺素能核（LC）视为 全局唤醒信号的来源，该信号通过更改整个操作来调节认知功能 整个中枢神经系统。这大概是通过〜1,600的一小部分来实现的 啮齿动物尖峰中的神经元同步。然而，最近，许多人的大规模录音 LC单元仅在麻醉大鼠中证明LC种群活动是 独立活动的不同合奏的细微差别模式。并行，化学遗传和 LC在行为啮齿动物中的光遗传操作表明，LC包含 提供特定认知功能的前脑电路特异性神经调节的神经元。这些 最近的进步迫使该领域记录行为动物的LC集合。但是，这需要 克服迄今为止有限的LC的行为动物中脑干运动的障碍 记录到多单元活动或一个单元。在这里，我们将建立超富林的可行性 多电极探针，称为“纳米电源线”（NETS），长达数月的LC集合 录音在未经麻醉的大鼠中。作为概念证明的研究，证明了网络的可行性， 我们仅在自由移动大鼠的视觉皮层中录制了〜150个单元，最多四个 月份。在这个项目中，我们旨在将512个电子植入头部固定的行为大鼠和 简单地记录100张LC单元，以及持续的唤醒/行为状态（瞳孔大小， 运动，口面运动等）。通过增加按订单记录的单位数量 大小，该项目将是LC研究的转变。我们的方法对 神经科学家记录其他脑干和皮层结构，其中记录了许多单一的单一记录 单位很困难。我们的总体目标是使用此R34来建立该方法，这将使一个 随后的针对性脑电路项目R01提交重点是LC合奏活动的作用 在慢性，长达数月的压力上是宝贵的认知僵化基础。