Wireless Magnetomechanical Neuromodulation of Targeted Circuits

摘要 在复杂行为过程中调节神经活动的可扩展方法对于正常行为的基础研究至关重要。 和异常的大脑功能在这里，我们的目标是开发一种无线磁机械神经调制技术， 适用于遗传上可识别的神经元群体的远程激励。这种方法将依赖于 的各向异性合成磁性纳米盘，以在弱慢变 磁场我们的初步研究结果表明，弱磁力矩强烈诱导活动 在感觉机械感受神经元中。这些观察将首先扩展到磁力学 通过SNAP标签或纳米抗体靶向纳米盘的遗传特异性脑神经元的神经调节 基于战略。我们的方法将进一步完善，通过敏感特定的神经元机械刺激， 机械敏感性阳离子通道TRPV 4（瞬时受体电位香草酸家族成员）的表达 4）。与依赖于由各向同性磁性纳米颗粒在高温度下耗散的热的磁热技术不同， 频率交变磁场，磁机械方法可以用现成的低- 功率电子器件，并且容易扩展到在啮齿动物中进行行为测定所需的体积， 在更大的模型中进行神经调节实验，包括未来的人类研究。我们将评估我们提出的 有针对性的磁机械神经调节方法，通过研究其塑造多巴胺的能力， 奖励和动机处理的小鼠模型中的依赖行为。

Abstract Scalable approaches to modulate neural activity during complex behaviors are essential to basic study of normal and aberrant brain function. Here we aim to develop a wireless magnetomechanical neuromodulation technique suitable for remote excitation of genetically identifiable neuronal populations. This approach will rely on the ability of anisotropic synthetic magnetic nanodiscs to transduce torques to cell membranes in weak slow-varying magnetic fields. Our preliminary findings indicate that weak magnetomechanical torques robustly induce activity in sensory mechanoreceptive neurons. These observations will be extended first to magnetomechanical neuromodulation of genetically specified brain neurons targeted with nanodiscs via SNAP-tag or nanobody- based strategies. Our approach will further be refined by sensitizing specific neurons to mechanical stimuli via expression of a mechanosensitive cation channel TRPV4 (transient receptor potential vanilloid family member 4). Unlike magnetothermal techniques that rely on heat dissipated by isotropic magnetic nanoparticles in high- frequency alternating magnetic fields, magnetomechanical approach can be implemented with off-the-shelf low- power electronics and is readily scalable to volumes necessary to conduct behavioral assays in rodents and neuromodulation experiments in larger models including future studies in humans. We will evaluate our proposed targeted magnetomechanical neuromodulation approach by investigating its ability to shape dopamine- dependent behaviors in a mouse model of reward and motivation processing.