title: Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound.
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 as central synaptic transmission we conclude US provides a powerful tool for remotely modulating brain circuit activity.
authors.affiliation: School of Life Sciences, Arizona State University, Tempe, Arizona, USA. wtyler@asu.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: Tyler
authors.forename: Yusuf
authors.initials: Y
authors.lastname: Tufail
authors.forename: Michael
authors.initials: M
authors.lastname: Finsterwald
authors.forename: Monica L
authors.initials: ML
authors.lastname: Tauchmann
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Olson
authors.forename: Cassondra
authors.initials: C
authors.lastname: Majestic
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000295:instrumentation / Q000379:methods; D005089:Exocytosis / Q000502:physiology; D051379:Mice; D008954:Models, Biological; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000295:instrumentation / Q000379:methods*; D050600:SNARE Proteins / Q000502:physiology; D015222:Sodium Channels / Q000378:metabolism / Q000502:physiology; D014465:Ultrasonics; D014463:Ultrasonography
chemical_list: D015220:Calcium Channels; D050600:SNARE Proteins; D015222:Sodium Channels