Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO 63130.
Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110.
Proc Natl Acad Sci U S A. 2024 Jun 25;121(26):e2402200121. doi: 10.1073/pnas.2402200121. Epub 2024 Jun 17.
Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations within specific subregions of the striatum. One notable feature of AhSonogenetics is its ability to flexibly stimulate either the left or right striatum in a single mouse. This flexibility is achieved by simply switching the acoustic metasurface in the wearable ultrasound device, eliminating the need for multiple implants or interventions. AhSonogentocs also integrates seamlessly with in vivo calcium recording via fiber photometry, showcasing its compatibility with optical modalities without cross talk. Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson's disease mice. This advancement is significant since many neurological disorders, including Parkinson's disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.
深入了解大脑功能并开发治疗神经疾病的方法,关键在于能够在不使用侵入性技术的情况下调节特定脑区的神经元群体。在这里,我们介绍了无植入、细胞类型特异性、空间精确且灵活的 Airy 光束声遗传学(AhSonogenetics),作为一种在自由活动的小鼠中进行的神经调节方法。AhSonogenetics 利用使用 3D 打印的 Airy 光束全息超表面制造的可穿戴超声设备。这些设备旨在操纵经过基因工程改造以表达超声敏感离子通道的神经元,从而能够精确调节特定神经元群体。通过动态地通过超声频率调谐来引导 Airy 光束的焦点,AhSonogenetics 能够调节纹状体特定亚区中的神经元群体。AhSonogenetics 的一个显著特点是它能够在单个小鼠中灵活地刺激左或右纹状体。这种灵活性是通过在可穿戴超声设备中简单地切换声超表面来实现的,无需多个植入物或干预。AhSonogentocs 还通过光纤光度法与体内钙记录无缝集成,展示了其与光学模式的兼容性,没有串扰。此外,AhSonogenetics 可以产生双焦点以进行双侧刺激,并减轻帕金森病小鼠的运动缺陷。这一进展意义重大,因为许多神经疾病,包括帕金森病,都涉及多个脑区的功能障碍。通过实现无侵入性程序的精确和灵活的细胞类型特异性神经调节,AhSonogenetics 为研究完整的神经回路提供了强大的工具,并为神经疾病提供了有前途的干预措施。
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