Interrogating Biophysical Mechanisms of Magnetogenetic Cell Stimulation at Radio Frequencies

探究射频刺激磁发生细胞的生物物理机制

• 批准号: 10596467
• 负责人: CHUNLEI LIU
• 金额: $ 51.03万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596467
• 关键词: Animal Model; Area; BRAIN initiative; Binding; Biophysical Process; Biophysics; Brain; Calcium; Cations; Cell Line; Cell membrane; Cells; Cellular Metabolic Process; Central Nervous System; Characteristics; Chemicals; Chimeric Proteins; Complex; Conflict (Psychology); DNA; Dependence; Electric Stimulation; Electromagnetic Fields; Electromagnetics; Energy Transfer; Family; Ferritin; Frequencies; Future; Goals; Heating; High temperature of physical object; In Situ; In Vitro; Ion Channel; Iron; Kininogens; Laws; Lipid Peroxidation; Lipids; Magnetic nanoparticles; Magnetism; Measures; Membrane; Methods; Modeling; Nature; Neurobiology; Neurons; Operative Surgical Procedures; Penetration; Permeability; Physics; Physiological; Process; Proteins; Protocols documentation; Reporting; Research; Safety; Signal Pathway; Specific qualifier value; Specificity; Stimulus; System; TRPV channel; TRPV1 gene; Techniques; Technology; Temperature; Thermodynamics; Tissues; Vanilloid; cell type; design; experimental study; improved; in vivo; magnetic field; mechanical force; neural stimulation; novel; optogenetics; particle; peroxidation; radio frequency; receptor; response; uptake; voltage; wireless

Abstract Magnetogenetics is a recently proposed method for stimulating cells using electromagnetic fields. In one approach, radio-frequency (RF) electromagnetic fields are applied to stimulate membrane channel proteins such as TRPV1 and TRPV4 that are attached to ferritins. The concept is highly attractive as it enables wireless neural stimulation without limitation on penetration depth or the requirement of invasive surgeries. If successful, RF- based magnetogenetics can provide a non-invasive approach for large-scale neural stimulation that can reach anywhere in the brain and achieve cellular specificity. This capability overcomes a significant limitation in other techniques such as electrical stimulation and optogenetics where stimulation is spatially restricted. However, while there have been several independent reports of experimental evidences for magnetogenetic effects using RF waves, the physical and neurobiological underpinnings of such effects remain unclear and controversial. Reported experiments have been conducted only in a few selected frequencies and amplitudes and the responses were mostly measured indirectly based on downstream physiological effects. The objective of the proposed project is to systematically characterize, model and validate the neurobiological and cellular responses upon RF stimulation in neurons expressing ferritin-attached TRPV1 and TRPV4 channels. Specifically, we aim to characterize these magnetogenetic channels of their: 1) neuronal responses to electrical and chemical stimuli and to RF stimulation over a wide range of frequencies and amplitudes; 2) temperature responses to RF stimulation at the protein, cytoplasmic membrane and cellular level; 3) cellular metabolic processes upon RF stimulation. We will systematically evaluate two novel working hypotheses of the underlying mechanisms. If successful, the project will characterize the cellular responses to RF stimulation, quantify activation thresholds and safety limits, establish standard protocols and elucidate the biophysical underpinnings of this reported RF- based magnetogenetic phenomenon. It would resolve a fundamental challenge in advancing this technology and guide a more rationale design and improvement of the techniques. Understanding the mechanisms of the initial reports of magnetogenetics would be a significant addition to the present ensemble of neuro-stimulation technologies such as electrical stimulation and optogenetics and contribute to one central goal of the BRAIN Initiative that is to develop new and improved perturbation technologies suitable for controlling specified cell types and circuits to modulate function in the central nervous system.

抽象的 磁化遗传学是一种使用电磁场刺激细胞的最近提出的方法。一个 方法，射频（RF）电磁场用于刺激膜通道蛋白这样 作为连接到铁蛋白的TRPV1和TRPV4。该概念非常有吸引力，因为它可以实现无线神经 刺激不限制穿透深度或侵入性手术的要求。如果成功，RF- 基于磁化遗传学可以为大规模神经刺激提供一种非侵入性方法 大脑中的任何地方并达到细胞特异性。这种能力克服了其他方面的重大限制 刺激受到空间限制的技术，例如电刺激和光遗传学。然而， 虽然有几个独立的报道，关于使用的实验证据 RF波，这种作用的物理和神经生物学基础仍然不清楚和有争议。 报告的实验仅在一些选定的频率和振幅中进行，并且 反应主要是根据下游生理效应间接测量的。目的 拟议的项目是系统地表征，建模和验证神经生物学和细胞反应 在表达铁蛋白连接的TRPV1和TRPV4通道的神经元中的RF刺激后。具体来说，我们的目标 为了表征它们的这些磁遗传通道：1）对电和化学刺激的神经元反应 并在各种频率和振幅上刺激RF刺激； 2）对RF的温度响应 刺激蛋白质，细胞质膜和细胞水平； 3）RF上的细胞代谢过程 刺激。我们将系统地评估两个基本机制的新型工作假设。如果 成功，该项目将表征对RF刺激的细胞反应，量化激活阈值 和安全限制，建立标准方案并阐明该RF-的生物物理基础 基于磁化现象。它将解决进步这项技术的基本挑战和 指导更多的理由设计和技术的改进。了解最初的机制 磁化遗传学的报道将是当前神经刺激合奏的重要补充 电刺激和光遗传学等技术，并为大脑的一个中心目标做出了贡献 开发新的和改进的扰动技术的计划，适合控制指定的单元 在中枢神经系统中调节功能的类型和电路。

项目成果

The Timing of Excitatory and Inhibitory Synapses Rules the Cerebellar Computation.

兴奋性和抑制性突触的时序决定小脑计算。

• DOI: 10.1523/jneurosci.1946-23.2024
• 发表时间: 2024
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Morales-Weil,Koyam

Evaluating methods and protocols of ferritin-based magnetogenetics.

• DOI: 10.1016/j.isci.2021.103094
• 发表时间: 2021-10-22
• 期刊: iScience
• 影响因子: 5.8
• 作者: Hernández-Morales M;Han V;Kramer RH;Liu C
• 通讯作者: Liu C