Remote regulation of neural activity

远程调节神经活动

• 批准号: 8821955
• 负责人: Sarah Amy Stanley
• 金额: $ 41.95万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-26 至 2015-05-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8821955
• 关键词: Address; Animals; Area; Behavior; Biological; Biomedical Engineering; Brain; Calcium; Cations; Cells; Characteristics; Chloride Ion; Clinical; Communities; Complex; Designer Drugs; Development; Drug Modulation; Electromagnetics; Endocrine; Exposure to; Ferritin; Goals; Heating; Hypothalamic structure; Implant; In Vitro; Individual; Ion Channel; Ions; Kinetics; Life; Ligands; Light; Magnetism; Mechanics; Mediating; Methods; Modification; Motor; Movement; Mus; Neurobiology; Neuroglia; Neurons; Neurosciences; Optical Methods; Organism; Penetration; Peripheral; Physiological; Point Mutation; Population; Publishing; Purkinje Cells; Resolution; Role; Signal Transduction; Slice; Staging; System; TRPV1 gene; Techniques; Technology; Temperature; Time; Tissues; Translations; Vanilloid; Viral; Viral Vector; Virus; Work; cell growth regulation; clinical application; efficacy testing; in vivo; iron oxide; magnetic field; nanoparticle; neuroregulation; new technology; optogenetics; patch clamp; public health relevance; radiofrequency; receptor; relating to nervous system; response; tool

 DESCRIPTION (provided by applicant): A fundamental goal of neuroscience is to understand the function(s) of defined neural populations in a complex organism. We propose to develop and validate a technology for non- invasive modulation of neural activity in vivo. There has been huge progress in developing tools for temporal regulation of neural activity. These techniques, from light activated channels to designer receptors, enable modulation of defined neural populations in vivo to examine their roles in many physiological functions. But current technologies have their limitations. Optical methods require permanent implants and activate only local neural populations while designer receptors and their specific ligands have a significantly slower time course. Ideally, tools would be capable of remote modulation of neural activity in local or dispersed neural populations at multiple stages of development with rapid temporal resolution. We address this challenge by using a distinctive combination of non-invasive radiowave and magnetic field signals, biological ferritin nanoparticles and bioengineered ion channels for non- invasive modulation of neural activity in freely moving animals. Radiofrequency or magnetic fields remotely modulate neurons that express nanoparticles formed in a modified ferritin shell. These are tethered to a modified ion channel, transient receptor potential vanilloid 1, TRPV1. Radiowaves or magnetic fields penetrate tissue to heat or move the nanoparticle respectively and activate TRPV1. Modifications of TRPV1 allow either neural activation or silencing. We will develop and validate tools for non-invasive activation and silencing of neural populations using viral vectors applicable to several species and demonstrate their utility in regulating complex behaviors. Specifically, we will 1) characterize the electrophysiological responses to RF and magnetic manipulation of neural populations in vitro, 2) examine the responses to RF or magnetic field modulation of hypothalamic neurons in vivo and compare them to optogenetic modulation and 3) determine the effects of modulating a neural population that is dispersed through a cortical lamina, the cerebellar Purkinje cells, in vivo in comparison to designer receptors exclusively activated by designer drugs (DREADD) modulation. Using bioengineered nanoparticles to transduce electromagnetic signals, we will develop a unique technology for targeted, non-invasive manipulation of neural activity that is applicable to local or dispersed cells through development. Our technology will be a valuable addition to the available tools to investigate the physiological roles of neural populations.

 描述（由申请人提供）：神经科学的基本目标是了解复杂生物体中定义的神经群的功能。我们建议开发和验证一种在体神经活动的非侵入性调制技术。在开发神经活动时间调节工具方面取得了巨大进展。这些技术，从光激活通道设计受体，使调制定义的神经群体在体内检查他们的角色在许多生理功能。但目前的技术有其局限性。光学方法需要永久性植入物，仅激活局部神经群体，而设计受体及其特定配体的时间进程明显较慢。理想情况下，工具将能够远程调制的神经活动在本地或分散的神经群体在多个阶段的发展与快速的时间分辨率。我们通过使用非侵入性无线电波和磁场信号、生物铁蛋白纳米颗粒和生物工程化离子通道的独特组合来应对这一挑战，以非侵入性地调节自由移动动物的神经活动。辐射或磁场远程调节神经元，表达在修饰的铁蛋白壳中形成的纳米颗粒。这些被拴系到一个修改的离子通道，瞬时受体电位香草素1，TRPV1。无线电波或磁场穿透组织以分别加热或移动纳米颗粒并激活TRPV 1。TRPV1的修饰允许神经激活或沉默。我们将开发和验证使用适用于几个物种的病毒载体进行神经群体的非侵入性激活和沉默的工具，并证明它们在调节复杂行为中的实用性。具体而言，我们将1）表征对体外神经群体的RF和磁操纵的电生理学响应，2）检查对体内下丘脑神经元的RF或磁场调制的响应，并将其与光遗传学调制进行比较，以及3）确定调制通过皮质层分散的神经群体，小脑浦肯野细胞，在体内与设计者受体仅由设计者药物（DREADD）调节激活相比。使用生物工程纳米粒子来识别电磁信号，我们将开发一种独特的技术，用于有针对性的，非侵入性的神经活动操纵，通过开发适用于本地或分散的细胞。 我们的技术将是一个有价值的除了可用的工具来调查神经群体的生理作用。