WIRELESS MAGNETO-MECHANICAL CONTROL OF NEURAL ACTIVITY MEDIATED BY MAGNETIC NANODISCS

神经活动的无线磁力控制 由磁性纳米盘介导 项目摘要/摘要 神经性疾病的治疗需要神经回路的细胞型特异性操作 精神疾病。对神经回路的精确控制将使神经调节的发展成为可能 治疗这些衰弱疾病的方法。现有的控制神经活动的技术提供了有限的可能性。 通过直接药物治疗对大脑回路的操纵受到血液选择性通透性的限制- 脑屏障，脑液快速清除，缺乏特异性，导致对 药物和不良副作用。电刺激和光遗传学为修复提供了可能 通过直接控制大脑回路动力学的神经功能障碍。然而，这两种技术都需要 破坏生物组织的可植入装置。细胞信号转导的微创控制 在神经系统和免疫系统的基础研究中正在探索磁场。基于无线方案 磁性纳米颗粒在高频交变磁场中的滞后加热 已经允许在体内调节神经活动和癌症治疗药物。尽管有这些进步，但 高频AMFS装置定标中潜在的非目标加热效应和挑战阻碍 磁热疗在生物医学研究中的普遍采用。在这里，我们提出了一种可扩展的磁电机- 由磁性纳米盘(MND)介导的远程控制神经活动的机械方案。MND将是 干涉光刻和模板辅助物理沉积技术制造批量生产 无毒、胶体稳定性高的MND。当与细胞膜接触时，MND将起到 将低频低幅度(20-50 mT，5-10赫兹)磁场转换为机械力的传感器。这 这项技术将在体外应用于控制从大鼠大脑分离的皮质神经元中的神经活动。此外， 我们将研究我们的技术，通过调节小鼠的神经活动来唤起小鼠的听觉驱动的恐惧行为 听觉皮质→杏仁核通路。听觉皮质对杏仁核脑回路的调制可能允许 开发非侵入性疗法来管理恐惧和焦虑相关的障碍。相比之下， 对于磁热方法，这里提出的系统为大容量提供了直接的可扩展性， 需要显著较低的磁能，并且能够调节细胞活动，而不依赖于 转基因。

WIRELESS MAGNETO-MECHANICAL CONTROL OF NEURAL ACTIVITY MEDIATED BY MAGNETIC NANODISCS PROJECT SUMMARY / ABSTRACT Cell-type specific manipulation of neural circuits is required for the treatment of neurological disorders and psychiatric conditions. Precise control of neural circuits will enable the development of neuromodulation therapies for these debilitating conditions. Existing technologies to control neural activity offer limited possibilities. Manipulation of brain circuits via direct drug treatment is restricted by the selective permeability of the blood- brain barrier, the rapid clearance of cerebral fluids and the lack of specificity which results in poor response to drugs and undesirable side effects. Electrical stimulation and optogenetics have open the possibility of repairing neural dysfunction through direct control of brain circuit dynamics. However, both technologies require implantable devices that are damaging to biological tissues. Minimally invasive control of cell signaling with magnetic fields is being explored in basic studies of the nervous and immune systems. Wireless schemes based on hysteretic heating of magnetic nanoparticles in high frequency alternating magnetic fields (AMFs) have already permitted modulation of neural activity and cancer theranostics in vivo. Despite these advances, the potential off-target heating effects and challenges in scaling of high-frequency AMFs apparatuses impede universal adoption of magnetic hyperthermia in biomedical research. Here we propose a scalable magneto- mechanical scheme for remote control of neural activity mediated by magnetic nanodiscs (MNDs). MNDs will be fabricated by interference lithography and template-assisted physical deposition technique to produce in bulk non-toxic MNDs with high colloidal stability. When interfaced with the cell membranes, MNDs will act as transducers of low frequency low amplitude (20-50 mT, 5-10 Hz) magnetic fields into mechanical forces. This technology will be applied in vitro to control neural activity in cortical neurons isolated from rat brains. Moreover, we will investigate our technology to evoke auditory-driven fear behavior in mice by modulating neural activity in the auditory cortex → amygdala pathway. Modulation of auditory cortex to amygdala brain circuits could allow the development of non-invasive therapies for the management of fear and anxiety-related disorders. In contrast to magneto-thermal approaches, the system proposed here offers straightforward scalability to large volumes, requires significantly lower magnetic energy, and is capable of modulating cell activity without reliance on transgenes.