Sreekanth Chalasani and his lab at the Salk Institute are primarily interested in behavior, and how neuronal circuits generate and produce certain behaviors. Their lab uses the roundworm, Caenorhabditis elegans (C. elegans), as their primary model system to study different types of behavior. C. Elegans has a much simpler nervous system, with only 302 neurons, which is substantially less compared to humans or other mammalian models and is easier to study. To study behavior, the current systems neuroscience field has multiple techniques to manipulate, monitor, and map existing neuronal populations. One of the most common techniques is optogenetics, which utilizes light in order to manipulate ion channels within neurons. However, optogenetic approaches require invasive surgical procedures in order to access deeper brain structures for light delivery. Most recently, Dr. Chalasani’s lab has been focused on developing a new technique called Sonogenetics, which utilizes ultrasound in order to manipulate targeted cells of interest.
Ultrasound is a widely used technique in clinical settings, as it is capable of traveling through skin and thin bone into deeper tissue. It thrives on being noninvasive, as well as being minimally damaging compared to other imaging methodologies. Ultrasound has also been used in research to stimulate clusters of neurons in vitro and neurons within other model organisms. This newly developed technique, Sonogenetics, is very similar to optogenetics, where light is used to selectively activate cells. However, sonogenetics utilizes low-frequency ultrasound, which is capable of traveling through the body with minimal scattering and signal loss. These ultrasound waves target a mechanotransduction channel, TRP-4, which is a calcium ion channel that is sensitive to low-pressure ultrasound. C. elegans normally express TRP-4 channels, which are opened with stretching of the body.
Normally, wild-type animals are insensitive to low-pressure ultrasound. However, when C. elegans were surrounded by gas-filled microbubbles, these microbubbles were effective in transducing the ultrasound stimuli. This ultrasound stimuli would cause a backward movement, which they call a reversal. They hypothesized that individual neurons could be activated through the TRP-4 channels due to the interaction between the ultrasound waves and the microbubbles. Shown in Figure 5a, animals lacking TRP-4 channels have a reduced number of reversals, suggesting that these TRP-4 channels are important for receiving ultrasound signal.
Most recently, Dr. Chalasani’s lab is focused on expanding Sonogenetics to the mice model as well, which will expand the available neuroscience techniques available for dissection of the nervous system. To hear more about the work being done in Dr. Chalasani’s lab, please join us at 4:00 pm Tuesday May 5th on Zoom.
____________________________________________________________________________________________Written by Caroline Jia, a 1st year Neuroscience MSTP Student, working in Sung Han’s laboratory at the Salk Institute