Remote excitation of neuronal circuits using low-intensity, low-frequency ultrasound

• Published in: PloS one 2008-10, Vol.3 (10), p.e3511-e3511
• Main Authors: Tyler, William J, Tufail, Yusuf, Finsterwald, Michael, Tauchmann, Monica L, Olson, Emily J, Majestic, Cassondra
• Format: Article
• Language: English
• Subjects: Animals; Biophysics/Experimental Biophysical Methods; Biophysics/Membrane Proteins and Energy Transduction; Biotechnology/Bioengineering; Brain; Brain slice preparation; Calcium; Calcium channels; Calcium channels (voltage-gated); Calcium Channels - physiology; Calcium signalling; Cell Biology/Neuronal and Glial Cell Biology; Cell Biology/Neuronal Signaling Mechanisms; Cells, Cultured; Channels; Circuits; Electric Stimulation - instrumentation; Electric Stimulation - methods; Exocytosis; Exocytosis - physiology; Growth factors; Health aspects; Hippocampus; Kinases; Life sciences; Mice; Models, Biological; Nerve Net - diagnostic imaging; Nerve Net - physiology; Neurodegeneration; Neurological Disorders; Neuromodulation; Neurons; Neurons - metabolism; Neurons - physiology; Neuroscience; Neuroscience/Neuronal and Glial Cell Biology; Neuroscience/Neuronal Signaling Mechanisms; Patch-Clamp Techniques - instrumentation; Patch-Clamp Techniques - methods; Physics/General Physics; Physiology/Cell Signaling; Physiology/Neuronal Signaling Mechanisms; Power; SNAP receptors; SNARE Proteins - physiology; Sodium; Sodium channels (voltage-gated); Sodium Channels - metabolism; Sodium Channels - physiology; Studies; Synaptic transmission; Tissues; Transcranial magnetic stimulation; Ultrasonic imaging; Ultrasonics; Ultrasonography; Ultrasound; Waveforms
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003511

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.