The research team headed by LI Yuezhou with ZJU’s School of Medicine collaborated with the research team headed by ZHENG Hairong with CAS’s Shenzhen Institute of Advanced Technology in research into ultrasonic control over neural activity. Their findings are published in the June 19 issue of the journal of Nano Letters.

External control over 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 mechanosensitive channel of large conductance (MscL). LI Yuezhou et al report MscL in rat hippocampal neurons in a primary culture and reveal that it can 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 is open 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.

This research opens up a new orientation for the application of ultrasonic control in neural studies and lays a foundation for the further development of genetic ultrasound.

Robert Desimone, the Doris and Don Berkey Professor of Neuroscience at the Massachusetts Institute of Technology, comments on this research as follows,

“The development of methods to use light to control the firing of neurons in the brain has revolutionized neuroscience research. But light based methods generally require a probe implanted in the brain to deliver the light. If one could use a noninvasive source of energy, such as ultrasound, to control neurons, this would have major research and clinical applications. The results of YE Jia et al with ultrasound look extremely promising, and I am sure they will stimulate more research to test the use of ultrasound in many neural applications, both basic and clinical.”