title: Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans.
abstract: A major challenge in neuroscience is to reliably activate individual neurons, particularly those in deeper brain regions. Current optogenetic approaches require invasive surgical procedures to deliver light of specific wavelengths to target cells to activate or silence them. Here, we demonstrate the use of low-pressure ultrasound as a non-invasive trigger to activate specific ultrasonically sensitized neurons in the nematode, Caenorhabditis elegans. We first show that wild-type animals are insensitive to low-pressure ultrasound and require gas-filled microbubbles to transduce the ultrasound wave. We find that neuron-specific misexpression of TRP-4, the pore-forming subunit of a mechanotransduction channel, sensitizes neurons to ultrasound stimulus, resulting in behavioural outputs. Furthermore, we use this approach to manipulate the function of sensory neurons and interneurons and identify a role for PVD sensory neurons in modifying locomotory behaviours. We suggest that this method can be broadly applied to manipulate cellular functions in vivo.
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Ibsen
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Ada
authors.initials: A
authors.lastname: Tong
authors.affiliation: Department of Bioengineering, Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Schutt
authors.affiliation: Department of Nanoengineering, Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Sadik
authors.initials: S
authors.lastname: Esener
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: Sreekanth H
authors.initials: SH
authors.lastname: Chalasani
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D007395:Interneurons / Q000378:metabolism / Q000502:physiology*; D008124:Locomotion / Q000502:physiology*; D045423:Microbubbles; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000502:physiology*; D050052:TRPC Cation Channels / Q000235:genetics*; D000069453:Ultrasonic Waves
chemical_list: D029742:Caenorhabditis elegans Proteins; D050052:TRPC Cation Channels; C489571:TRPC4 ion channel