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 整个中枢神经系统大概是通过这个仅约 1,600 个的小集合来实现的。 然而，最近首次大规模记录了许多啮齿类动物的神经元同步放电。 在麻醉大鼠中同时进行 LC 单个单位证明 LC 群体活性包括 独立活跃的不同整体的微妙模式。 对行为啮齿类动物的 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。 最近的进展迫使该领域记录行为动物的 LC 系综，但这需要记录。 克服行为动物脑干运动的障碍，迄今为止限制了 LC 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 作为一项证明 NET 可行性的概念验证研究， 我们在自由移动的大鼠的视觉皮层中同时记录了约 150 个单个单位，持续时间长达 4 个 在这个项目中，我们的目标是在头部固定的行为大鼠的 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）。 规模，这个项目将对液相色谱研究产生变革，我们的方法将广泛用于 神经科学家在其他脑干和皮质下结构中进行记录，其中记录了许多单个 我们的总体目标是使用这个 R34 来建立方法，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。