Vision relies on the photochemical response of specialized cells in the retinas of the eyes to light stimuli. Aging-dependent or accidental loss of vision may involve damage to these retinal cells and their light-sensing proteins. Researchers are developing methods to manipulate the activity of specific cells, such as neurons, in living animal models to cure diseases attributed to the loss of cellular function. One such technique is optogenetics in which cells are genetically engineered to express light-sensitive proteins and react to light. However, though optogenetics has a huge potential, it is invasive and requires surgery to implant a fiber optic cable to deliver the light to the cells.
Recently a team of neuroscientists headed by Prof. Sreekanth H. Chalasani at The Salk Institute for Biological Studies, La Jolla, California, has developed a technique that they call ‘sonogenetics’ ultrasound to stimulate individual neuronal cells in nematode worms (C. elegans). The technique relies on engineering brain cells expressing non-endogenous, touch-sensitive membrane ‘channel’ protein, which is responsive to ultrasonic pulse that results in switching on of neurons and downstream molecular signaling resulting in a mechano-sensory response.
Sonogenetics uses >20,000 Hz sound waves these are the same type of waves used in medical sonograms instead of light. These ultrasound waves can even pass through bones and reach cells deep inside the tissue. One major caveat of using ultrasound has been that the minimum focal zone of the ultrasound is larger than an individual cell. As a result, the ultrasound wave stimulus can have a non-specific effect resulting in stimulation of a population of cells. In ‘sonogenetics’ ultrasound technique this problem was meticulously overcome first by using gas-filled microbubbles to amplify the waves and then by using genetically modified cells in worms, which are hypersensitive to the ultrasound. To generate these genetically modified cells, researchers added a membrane ion channel TRP-4 to the neurons of C. elegans. The membrane ion channel opens up in response to the mechanical force of the ultrasound waves, which activates the cell. As a result, the genetically-modified nematodes on an agar plate responded to a pulse of ultrasound by changing their direction of movement on the plate.
Authors hope that this technique can ultimately be used in humans. Authors are planning to test this in mice that do not endogenously produce TRP-4 channel, so there is a possibility of the protein behaving differently. Researchers believe that sonogenetics might have other applications to treat a range of neurological diseases.
Dr. Chalasani in a press interaction said, “It could be used as an alternative to deep brain stimulation, a new treatment that uses implanted electrodes in the brain to alleviate symptoms of patients suffering from Parkinson’s disease and other neurological disorders. The idea would be to deliver ultrasound-sensitive channel to the appropriate target safely – perhaps using a virus – then we could stimulate those targets without any surgery.”
For a long time, one of the biggest challenges in neuroscience has been to activate reliably individual neurons, which is confounded by the fact that it is even more tedious to do it when the target areas are in deeper brain regions. Sonogenetics uses ultrasound as an alternative to invasive methods in the form of a non-invasive trigger to activate specific, ultrasonically sensitized neurons.
It is yet to be seen if sonogenetics can be as effective in bedside care as it seems to be in bench-side research.
The video shows how the nematodes change direction the moment they are blasted with sonic pulses.