Munshi Rahul, Qadri Shahnaz M, Pralle Arnd
Department of Physics, University at Buffalo, Buffalo, NY, United States.
Front Neurosci. 2018 Aug 14;12:560. doi: 10.3389/fnins.2018.00560. eCollection 2018.
Determining the role and necessity of specific neurons in a network calls for precisely timed, reversible removal of these neurons from the circuit via remotely triggered transient silencing. Previously, we have shown that alternating magnetic field mediated heating of magnetic nanoparticles, bound to neurons, expressing temperature-sensitive cation channels TRPV1 remotely activates these neurons, evoking behavioral responses in mice. Here, we demonstrate how to apply magnetic nanoparticle heating to silence target neurons. Rat hippocampal neuronal cultures were transfected to express the temperature gated chloride channel, anoctamin 1 (TMEM16A). Spontaneous firing was suppressed within seconds of alternating magnetic field application to anoctamin 1 (TMEM16A) channel expressing, magnetic nanoparticle decorated neurons. Five seconds of magnetic field application leads to 12 s of silencing, with a latency of 2 s and an average suppression ratio of more than 80%. Immediately following the silencing period spontaneous activity resumed. The method provides a promising avenue for tether free, remote, transient neuronal silencing for both scientific and therapeutic applications.
确定特定神经元在网络中的作用和必要性，需要通过远程触发的瞬时沉默，精确地定时、可逆地将这些神经元从回路中移除。此前，我们已经表明，与表达温度敏感阳离子通道TRPV1的神经元结合的磁性纳米颗粒，通过交变磁场介导的加热可远程激活这些神经元，从而在小鼠中引发行为反应。在此，我们展示了如何应用磁性纳米颗粒加热来沉默目标神经元。将大鼠海马神经元培养物转染以表达温度门控氯离子通道anoctamin 1（TMEM16A）。在对表达anoctamin 1（TMEM16A）通道、装饰有磁性纳米颗粒的神经元施加交变磁场后的几秒钟内，自发放电就受到了抑制。施加5秒钟磁场可导致12秒的沉默，延迟为2秒，平均抑制率超过80%。沉默期过后，自发活动立即恢复。该方法为科学和治疗应用中的无束缚、远程、瞬时神经元沉默提供了一条有前景的途径。
