remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound远程神经电路使用低强度的激发,低频超声波.pdfVIP

Remote Excitation of Neuronal Circuits Using Low- Intensity, Low-Frequency Ultrasound 1,2 1 3 1 1 William J. Tyler *, Yusuf Tufail , Michael Finsterwald , Monica L. Tauchmann , Emily J. Olson , Cassondra Majestic1 1 School of Life Sciences, Arizona State University, Tempe, Arizona, United States of America, 2 Harrington Department of Bioengineering, Arizona State University, Tempe, Arizona, United States of America, 3 Array Therapeutic, Scottsdale, Arizona, United States of America Abstract Possessing the ability to noninvasively elicit brain circuit activity yields immense experimental and therapeutic power. Most currently employed neurostimulation methods rely on the somewhat invasive use of stimulating electrodes or photon- emitting devices. Due to its ability to noninvasively propagate through bone and other tissues in a focused manner, the implementation of ultrasound (US) represents a compelling alternative approach to current neuromodulation strategies. Here, we investigated the influence of low-intensity, low-frequency ultrasound (LILFU) on neuronal activity. By transmitting US waveforms through hippocampal slice cultures and ex vivo mouse brains, we determined LILFU is capable of remotely and noninvasively exciting neurons and network activity. Our results illustrate that LILFU can stimulate electrical activity in neurons by activating voltage-gated sodium channels, as well as voltage-gated calcium channels. The LILFU-induced changes in neuronal activity were sufficient to trigger SNARE-mediated exocytosis and synaptic transmission in hippocampal circuits. Because LILFU can stimulate electrical activity and calcium signaling in neurons as well