Multi-Site Non-Invasive Magnetothermal Excitation and Inhibition of Deep Brain Structures

脑深部结构的多位点非侵入性磁热激发和抑制

• 批准号: 9229172
• 负责人: Polina O Anikeeva
• 金额: $ 87.59万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-26 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9229172
• 关键词: Animal Behavior; Animals; Area; Automobile Driving; Behavior; Behavior Control; Behavioral; Biological; Biological Assay; Biological Models; Brain; Brain region; Buffaloes; Calcium; Cells; Chemistry; Chloride Channels; Clinical; Collaborations; Complex; Consumption; Deep Brain Stimulation; Electric Stimulation; Electromagnetics; Electrophysiology (science); Engineering; Evaluation; Fiber; Food; Frequencies; Gambling; Habenula; Heating; Hippocampus (Brain); Image; Implant; In Vitro; Individual; Injection of therapeutic agent; Intervention; Ion Channel; Laboratories; Lateral; Learning; Left; Link; Magnetic nanoparticles; Magnetism; Maps; Mental Depression; Midbrain structure; Movement; Mus; Neural Inhibition; Neurons; Nucleus Accumbens; Optics; Pattern; Penetration; Photometry; Population; Predisposition; Property; Psychiatrist; Rattus; Reading; Resolution; Rewards; Rodent; Shapes; Signal Transduction; Site; Specificity; Structure; Substance abuse problem; TRPV1 gene; Technology; Training; Transducers; Transfection; Transgenic Mice; Translations; Ultrasonics; Ultrasonography; Ventral Tegmental Area; Vibrissae; Wireless Technology; abstracting; awake; barrel cortex; base; capsaicin receptor; cell type; designer receptors exclusively activated by designer drugs; dopaminergic neuron; driving behavior; experience; genetic approach; in vivo; magnetic field; minimally invasive; multi-photon; nanomaterials; nanoparticle; nanoscale; neuroregulation; novel; optogenetics; particle; preference; relating to nervous system; temporal measurement; tool

Abstract This project seeks to develop a wireless, minimally invasive bi-directional deep brain stimulation technology based on remote heating of magnetic nanoparticles. Reliably modulating the activity of specific neuronal populations is essential to establishing causal links between neural firing patterns and observed behaviors. Electrical stimulation, as well as its recent non-invasive alternatives, ultrasound and electromagnetic induction, do not discriminate between cell types and have limited spatial resolution. Genetic approaches such as DREADDs and optogenetics enable neural excitation and inhibition with exquisite precision in specific cell populations. However, they require long-term indwelling hardware (limiting clinical translation) or lack temporal resolution. In this project, we propose to evaluate a nanoparticle-based technology that can access the deep brain regions, excite and inhibit neurons, and be fully wireless after initial injection. The Anikeeva (MIT) and Pralle (SUNY Buffalo) groups have recently shown that heat dissipation by magnetic nanoparticles (MNPs) in alternating magnetic fields (AMFs) can trigger heat-sensitive capsaicin receptor TRPV1 and heat-sensitive chloride channel anoctamine 1 (ANO1), respectively. These, in turn, can depolarize or silence neurons, and we have preliminary evidence for effects both in vitro and in vivo. Finally, the Anikeeva group has made advances in nanomaterials chemistry that enables multiplexing: independent heating of multiple MNP types (implying control of multiple neighboring neural populations) using AMF with distinct amplitudes and frequencies. Our objective is to combine these technologies into a "magnetothermal toolbox" and demonstrate its ability to shape animal behavior, by manipulating a well-characterized midbrain reward circuit. We will refine the ANO1 inhibitory technology and demonstrate control of place aversion in mice (Aim 1), then merge this technology with TRPV1-facilitated excitation in context of magnetic multiplexing to show bi-directional control of place aversion/preference (Aim 2). From this proof of concept, Aim 3 seeks to demonstrate that the toolkit can also control a more complex behavior (gambling/ probabilistic reward learning) in a larger species (rat). We will carry out this project through a tightly integrated combination of expertise in nanoscale engineering (Anikeeva, Pralle), targeted neural modulation (Anikeeva, Pralle), behavior manipulation through midbrain modulation (Widge) and clinical psychiatric deep brain stimulation (Widge).

抽象的 该项目旨在开发无线，微创双向深度脑刺激技术 基于磁性纳米颗粒的远程加热。可靠地调节特定神经元的活性 种群对于在神经解火模式和观察到的行为之间建立因果关系至关重要。 电刺激以及其最近的非侵入性替代方案，超声和电磁诱导， 不要区分细胞类型，并且空间分辨率有限。诸如遗传方法 恐惧和光遗传学在特定细胞中以精确的精度启用神经激发和抑制作用 人群。但是，它们需要长期留置硬件（限制临床翻译）或缺乏时间 解决。在这个项目中，我们建议评估一种基于纳米颗粒的技术，该技术可以访问深度 大脑区域，激发和抑制神经元，并在初次注射后完全无线。 Anikeeva（麻省理工学院）和 Pralle（SUNY BUFFALO）组最近表明，磁性纳米颗粒（MNP）的热量耗散 交替的磁场（AMF）可以触发热敏性辣椒素受体TRPV1和热敏感 氯化通道阳离子1（ANO1）分别。这些反过来可以去极化或沉默神经元，我们 在体外和体内都有初步证据。最后，Anikeeva集团取得了进步 在纳米材料的化学中，可以实现多重化：多种MNP类型的独立加热（暗示 使用具有不同幅度和频率的AMF控制多个相邻神经种群）。我们的 目的是将这些技术组合到“磁热工具箱”中，并证明其 通过操纵良好的中脑奖励电路来塑造动物行为的能力。我们将完善 ANO1抑制技术并证明对小鼠的位置厌恶的控制（AIM 1），然后合并 在磁多路复用的背景下，具有TRPV1-核激发的技术，以显示对的双向控制 放置/偏好（目标2）。从这个概念证明中，AIM 3试图证明该工具包可以 还控制较大物种（大鼠）中更复杂的行为（赌博/概率奖励学习）。我们将 通过纳米级工程专业知识的紧密组合来执行该项目（Anikeeva， Pralle），靶向神经调制（Anikeeva，Pralle），通过中脑调节操纵行为 （Widge）和临床精神病深脑刺激（Widge）。