Sonogenetics 2.0

声遗传学2.0

• 批准号: 10734960
• 负责人: Hong Chen
• 金额: $ 64.14万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-15 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10734960
• 关键词: 3D Print; Acoustics; Address; Animals; Area; Benchmarking; Biological; Biomedical Engineering; Brain; Brain Diseases; Brain region; Cell membrane; Cell physiology; Collaborations; Communities; Corpus striatum structure; Data; Dependovirus; Development; Device Designs; Devices; Dopamine D1 Receptor; Drug Delivery Systems; Engineering; Exhibits; Focused Ultrasound; Gene Delivery; Genetic; Genetic Engineering; Goals; Human; Injections; Intranasal Administration; Investigation; Ion Channel; Ions; Laboratories; Light; Location; Mediating; Microbubbles; Modality; Molecular Probes; Motor; Mus; Mutagenesis; Neurons; Neurosciences; Neurosciences Research; Operative Surgical Procedures; Penetration; Performance; Population; Process; Property; Public Health; Publishing; Research; Research Personnel; Research Project Grants; Resolution; Rodent; Safety; Serotyping; Sonication; Structure; TRPV1 gene; Techniques; Technology; Tissues; Transducers; Translating; Ultrasonic Therapy; Ultrasonic Transducer; Ultrasonics; Validation; Variant; Viral Vector; adeno-associated viral vector; cell type; efficacy evaluation; free behavior; genetic manipulation; improved; infancy; innovation; lens; millisecond; mind control; motor control; multidisciplinary; mutant; neural; neural circuit; neuroregulation; next generation; optogenetics; response; technology development; tool; translational potential; ultrasound

PROJECT SUMMARY/ABSTRACT Achieving noninvasive, cell-type-specific, and spatially precise neuromodulation remains to be a major challenge in the development of neuromodulation technologies. The objective of this project is to develop Sonogenetics 2.0, the next-generation sonogenetic technique for cell-type-specific, spatially precise neuromodulation in the whole brain of freely behaving animals without intracranial surgery. Sonogenetics 2.0 employs low-intensity focused ultrasound (FUS) combined with microbubbles to deliver intranasally administered adeno-associated viruses (AAVs) to the FUS-targeted brain region with minimal systemic exposure. It then utilizes FUS sonication to remotely activate the expressed ultrasound-sensitive ion channels encoded by the AAVs and thereby controls the activity of AAV-transduced neurons. Sonogenetics 2.0 addresses three critical barriers to developing sonogenetics: the lacks molecular probes with optimized ultrasound sensitivity (Aim 1), requires surgical injection of viral vectors to express the probes (Aim 2), and has a low spatial resolution in delivering ultrasound in the mouse brain (Aim 3). Sonogenetics 2.0 will be independently validated by neuroscience laboratories and benchmarked with optogenetics (Aim 4). The proposed Sonogenetics 2.0 is significant because technological breakthroughs are urgently needed to fulfill the great potential of sonogenetics. Sonogenetics 2.0 provides a complementary tool to existing neuromodulation techniques with the potential to be translated to large animals and humans. A multidisciplinary team with combined expertise in ultrasound device design, ion channel engineering, neuromodulation, and neuroscience is well suited to this project. This project is innovative because Sonogenetics 2.0 is the first-in-class ultrasound tool for completely noninvasive and cell-type-specific neuromodulation by combining noninvasive genetic construct delivery with noninvasive activation of transduced neurons. The proposed research is expected to have a sustained, powerful impact in the research field of sonogenetics and provide the neuroscience community with a transformative tool that can be widely used to advance our current capabilities in investigating cell-type-specific processes in intact mammalian brains.

项目总结/摘要 实现非侵入性，细胞类型特异性和空间精确的神经调节仍然是一个主要的问题。 神经调节技术发展的挑战。该项目的目标是开发 Sonogenetics 2.0，用于细胞类型特异性、空间精确性 在没有颅内手术的自由行为动物的整个大脑中的神经调节。Sonogenetics 2.0 采用低强度聚焦超声（FUS）结合微泡， 腺相关病毒（AAV）的FUS靶向脑区域，以最小的全身暴露。然后它 利用FUS超声处理远程激活表达的超声敏感离子通道， 腺相关病毒，从而控制腺相关病毒转导的神经元的活动。Sonogenetics 2.0解决了三个关键问题 发展声遗传学的障碍：缺乏具有优化超声灵敏度的分子探针（目标1）， 需要手术注射病毒载体来表达探针（Aim 2），并且在 在小鼠大脑中传递超声波（Aim 3）。Sonogenetics 2.0将由以下人员独立验证： 神经科学实验室和基准与光遗传学（目标4）。Sonogenetics 2.0是 重要的是，迫切需要技术突破，以实现巨大的潜力， 声音遗传学。Sonogenetics 2.0为现有的神经调节技术提供了一种补充工具， 有可能转化为大型动物和人类。一个多学科的团队，具有综合的专业知识， 超声设备设计、离子通道工程、神经调节和神经科学非常适合于此 项目这个项目是创新的，因为Sonogenetics 2.0是一流的超声工具，完全 非侵入性和细胞类型特异性神经调节 转导神经元的非侵入性激活。预计这项研究将产生持续、有力的 在声遗传学研究领域的影响，并提供一个变革性的工具，神经科学界 这可以广泛用于提高我们目前在研究细胞类型特异性过程中的能力， 哺乳动物的大脑