Children's Hospital and Department of Biophysics, NHC and CAMS Key Laboratory of Medical Neurobiology , Zhejiang University School of Medicine , Hangzhou , Zhejiang 310058 , China.
Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Key Laboratory for MRI , Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen , 518005 , China.
Nano Lett. 2018 Jul 11;18(7):4148-4155. doi: 10.1021/acs.nanolett.8b00935. Epub 2018 Jun 19.
Externally controlling the excitation of a neuronal subset through ion channels activation can modulate the firing pattern of an entire neural circuit in vivo. As nanovalves in the cell membrane, ion channels can be opened by light (optogenetics) or ultrasonic (sonogenetics) means. A thoroughly analyzed force sensor is the Escherichia coli mechano sensitive channel of large conductance (MscL). Here we expressed MscL in rat hippocampal neurons in a primary culture and showed that it could be activated by low-pressure ultrasound pulses. The gain-of-function mutation, I92L, sensitized MscL's sonic response, triggering action potentials at a peak negative pressure as low as 0.25 MPa. Further, the I92L MscL reliably elicited individual spikes by timed brief pulses, making excitation programmable. Because MscL opens to tension in the lipid bilayer, requiring no other proteins or ligands, it could be developed into a general noninvasive sonogenetic tool to manipulate the activities of neurons or other cells and potential nanodevices.
通过离子通道激活来外部控制神经元亚群的兴奋，可以在体内调节整个神经网络的发放模式。作为细胞膜上的纳米阀门，离子通道可以通过光（光遗传学）或超声（声遗传学）手段来开启。一种经过彻底分析的力传感器是大肠杆菌大电导机械敏感通道（MscL）。在这里，我们在原代培养的大鼠海马神经元中表达了 MscL，并证明它可以被低强度超声脉冲激活。功能获得性突变 I92L 使 MscL 的声响应变得敏感，在峰值负压低至 0.25 MPa 时即可引发动作电位。此外，I92L MscL 通过定时短暂脉冲可靠地引发单个尖峰，使兴奋具有可编程性。因为 MscL 对脂质双层中的张力开放，不需要其他蛋白质或配体，因此它可以开发成为一种通用的非侵入性声遗传学工具，用于操纵神经元或其他细胞的活动以及潜在的纳米器件。
