Magnetic Modulation on Targeted Neural Circuits in Autism

对自闭症目标神经回路的磁调制

• 批准号: 10598502
• 负责人: Siyuan Rao
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10598502
• 关键词: Advisory Committees; Affect; Award; Behavior assessment; Behavioral; Behavioral Assay; Biological Assay; Brain; Callithrix; Chemicals; Chemistry; Child; Clustered Regularly Interspaced Short Palindromic Repeats; Code; Committee Members; Communities; Diagnosis; Disparate; Electronics; Engineering; Ensure; Equilibrium; Etiology; Functional disorder; Future; Genes; Glutamate Metabolism Pathway; Glutamates; Goals; Human; Interdisciplinary Study; Intervention; Investigation; Knowledge; Laboratory Research; Lead; Ligands; Light; Link; Magnetic nanoparticles; Magnetism; Mentors; Mission; Modeling; Molecular; Mus; Mutation; Nanotechnology; Neuromodulator; Neurons; Neurosciences; Nucleic Acids; Outcome; Pathology; Pathway interactions; Penetration; Phase; Phase Transition; Phenotype; Population; Prevalence; Property; Protocols documentation; Research; Resources; Risk; Rodent; Science; Shapes; Site; Social Behavior; Social Interaction; Source; Specificity; Structure; Supervision; Surface; Synapses; System; Techniques; Technology; Testing; Training; Transgenic Mice; Viral; Wild Type Mouse; Work; atmospheric sciences; autism spectrum disorder; awake; behavior observation; behavior test; behavioral outcome; behavioral phenotyping; behavioral study; brain research; career; cell type; chemical synthesis; design; effective therapy; empowerment; experience; flexibility; gene therapy; genetic manipulation; implantation; improved; liposome vector; magnetic field; minimally invasive; mouse model; nanocarrier; nervous system disorder; neural; neural circuit; neurobehavioral; neurobehavioral test; neuromechanism; neurophysiology; neuroregulation; non-viral gene delivery; nonhuman primate; optogenetics; pharmacologic; post-doctoral training; professor; programs; receptor; remote control; scientific atmosphere; side effect; skills; social; social deficits; theranostics; tool; translation to humans; translational therapeutics; wireless

Project Summary and Abstract My overall career goal is to establish an independent research program focused on leveraging cutting-edge technologies of materials engineering, genetic manipulation and neurobehavioral science to study neural circuits underlying autism spectrum disorders (ASDs). I hypothesize that a remotely controlled magnetic neuromodulation tool will link precise circuit-level neural modulation to behavioral outcomes, and thus empower neural circuitry interrogation with systems neuroscience. To realize this goal, I have received training in extensive research fields including materials engineering, nanotechnology, cellular neurophysiology, and neuroscience. With this award, in my future career I will open up a new interdisciplinary research pathway of developing remotely controlled magnetic tools that enable pharmacological and gene-editing intervention on specific neural circuits along with the behavioral assessment on freely moving mice and awake, untethered non-human primates (NHPs). In the mentored phase, I will work under the supervision of Professor Polina Anikeeva - an expert in optoelectronic and magnetic neural interfaces, with the guidance of my advisory committee consisting of Professors Guoping Feng, Feng Zhang, Mriganka Sur, and Zhigang He. With their strong supports, I will receive additional training in gene editing, social behavioral test design and experimental experience with autism models of mice and marmosets, which will equip me with the knowledge and skills necessary to further the study of neural underpinnings of ASDs and launch my independent career. The work in mentored phase will be done at the Research Laboratory of Electronics and the McGovern Institute for Brain Research at MIT, which offer an active multidisciplinary research atmosphere, expansive infrastructural resources and a valuable intellectual community necessary for the implementation of the proposed project. During my Simons postdoctoral training at MIT, I established a chemomagnetic technique to pharmacologically modulate identifiable neural populations with behavioral assessment in freely moving mice. Hence, my immediate goal is to advance this technique into a multiplexed toolkit that enables multiple-site bidirectional control of circuit-level neural modulation. In Aim 1, I will improve the chemical synthesis of magnetic nanoparticles (MNPs) and liposomal nanocarriers to enable multiplexing control with paired ligand-receptors under disparate magnetic field conditions and implement the multiple-site neural modulation of brain structures that coordinate social behaviors. Next (Aim 2), I will advance this magnetic technique with gene editing approaches to enable non-viral gene delivery to cell-type specific neural circuits relevant to social processing. In the independent phase (Aim 3), I will validate the magnetic modulation on the targeted neural circuits to ameliorate social behavior deficits in transgenic mice, e.g. Shank3- /-. With the advanced magnetic electronics apparatuses, I will further adapt this technique to social interaction assessment in marmosets and introduce a potential magnetic field-assisted theranostic platform for ASDs.

项目概要和摘要 我的总体职业目标是建立一个独立的研究计划，专注于利用尖端技术， 利用材料工程、基因操作和神经行为科学等技术研究神经回路 自闭症谱系障碍（ASD）的潜在原因。我假设一个远程控制的磁力 神经调节工具将把精确的电路级神经调节与行为结果联系起来， 系统神经科学的神经回路研究为了实现这一目标，我接受了广泛的培训， 研究领域包括材料工程、纳米技术、细胞神经生理学和神经科学。 有了这个奖项，在我未来的职业生涯中，我将开辟一条新的跨学科研究道路， 远程控制的磁性工具，使药理学和基因编辑干预特定的神经 沿着对自由活动的小鼠和清醒的、未拴系的非人灵长类动物的行为评估 （NHPs）。在指导阶段，我将在Polina Anikeeva教授的监督下工作-他是一位专家， 光电和磁神经接口，在我的顾问委员会的指导下， 冯国平、张峰、苏姆里甘卡、何志刚教授。在他们的大力支持下，我将获得 在基因编辑、社会行为测试设计和自闭症模型实验经验方面的额外培训 的老鼠和绒猴，这将使我具备必要的知识和技能，以进一步研究 自闭症的神经基础并开始我独立的事业指导阶段的工作将在 麻省理工学院电子研究实验室和麦戈文大脑研究所， 活跃的多学科研究氛围，广阔的基础设施资源和宝贵的知识分子 社区为实施拟议项目所需。在西蒙斯的博士后培训期间， 麻省理工学院，我建立了一个化学磁技术， 在自由活动的小鼠中进行行为评估。因此，我的直接目标是将这项技术推广到 一个多路复用工具包，使多站点双向控制电路级神经调制。在目标1中， 将改善磁性纳米颗粒（MNP）和脂质体纳米载体的化学合成， 在完全不同的磁场条件下用配对的配体-受体进行多路复用控制，并实现 协调社会行为的大脑结构的多点神经调节。下一步（目标2），我将推进 这种磁技术与基因编辑方法，使非病毒基因传递到细胞类型特异性 与社会处理相关的神经回路在独立阶段（目标3），我将验证磁 调节靶向神经回路以改善转基因小鼠中的社会行为缺陷，例如Shank 3- /-.随着先进的磁电子仪器，我将进一步适应这种技术，以社会交往 评估在绒猴，并介绍了一个潜在的磁场辅助治疗诊断平台的自闭症。

项目成果

A nanoscale inorganic coating strategy for stabilizing hydrogel neural probes in vivo.

• DOI: 10.1039/d3tb00710c
• 发表时间: 2023-07
• 期刊: Journal of materials chemistry. B
• 作者: Sizhe Huang;Sabrina Urbina Villafranca;Iyanah Mehta;Omri Yosfan;Eunji Hong;Anyang Wang;N. Wu;Qianbin Wang;Siyuan Rao

Hydrogel fibers that enable optogenetic pain inhibition during locomotion.

水凝胶纤维可在运动过程中抑制光遗传学疼痛。

• DOI: 10.1038/s41592-023-02022-7
• 发表时间: 2023
• 期刊: Nature methods
• 影响因子: 48

Material Engineering Platform for Next Generation of Neurobiological Interfaces.

• DOI: 10.1021/accountsmr.0c00103
• 发表时间: 2021-05-28
• 期刊: Accounts of materials research
• 影响因子: 14.6
• 作者: Rao S;Qiu J
• 通讯作者: Qiu J