Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
Nat Biomed Eng. 2018 Jul;2(7):475-484. doi: 10.1038/s41551-018-0258-2. Epub 2018 Jul 9.
Neurological and psychiatric disorders are often characterized by dysfunctional neural circuits in specific regions of the brain. Existing treatment strategies, including the use of drugs and implantable brain stimulators, aim to modulate the activity of these circuits. However, they are not cell-type-specific, lack spatial targeting or require invasive procedures. Here, we report a cell-type-specific and non-invasive approach based on acoustically targeted chemogenetics that enables the modulation of neural circuits with spatiotemporal specificity. The approach uses ultrasound waves to transiently open the blood-brain barrier and transduce neurons at specific locations in the brain with virally encoded engineered G-protein-coupled receptors. The engineered neurons subsequently respond to systemically administered designer compounds to activate or inhibit their activity. In a mouse model of memory formation, the approach can modify and subsequently activate or inhibit excitatory neurons within the hippocampus, with selective control over individual brain regions. This technology overcomes some of the key limitations associated with conventional brain therapies.
神经和精神疾病的特征通常是大脑特定区域的神经回路功能失调。现有的治疗策略，包括使用药物和可植入脑刺激器，旨在调节这些回路的活动。然而，它们不是针对特定细胞类型的，缺乏空间靶向性或需要侵入性程序。在这里，我们报告了一种基于声靶向化学遗传学的细胞类型特异性和非侵入性方法，该方法能够以时空特异性方式调节神经回路。该方法使用超声波短暂打开血脑屏障，并通过病毒编码的工程化 G 蛋白偶联受体在大脑的特定位置转导神经元。随后，经过工程改造的神经元对系统给予的设计化合物做出反应，以激活或抑制其活性。在记忆形成的小鼠模型中，该方法可以改变海马体中的兴奋性神经元，随后激活或抑制其活性，并对单个脑区进行选择性控制。这项技术克服了与传统脑疗法相关的一些关键限制。
