The Nematode worm, Caenorhabditis elegans, more commonly referred to as C. Elegans, has long been used as a model organism in many areas of biological research. The reasons for this include the fact that scientists know the exact fate of every cell in its development. It also has a short life cycle length, well understood molecular genetics and finally – the most obvious reason – it is almost entirely see-through. Scientists have now discovered, using this model system they are able to use sound waves to influence neuronal activity and activate, as well as control brain cells.
Previous research has shown that cells can be similarly stimulated using light-termed optogenetics. However, there have been a number of limitations associated with this method, primarily the lack of penetrating power, and the characteristic scatter associated with light. As a result its use in higher organisms to influence brain activity requires invasive use of fibre optics.
The new method, called sonogenetics, works by using ultrasound to stimulate neurons. A specific gene expressed in the neurons, which can also be transgenically introduced with the same subsequent observations, encodes a special channel protein (TRP4) that opens when the cell membrane is stretched. This causes a neuronal response. For this to happen, the worms had to be introduced to a microbubble environment, in which tiny bubbles helped to amplify the ultrasound effect through oscillation. This would appear to be the first obstacle for mammalian use; however, these special bubbles can be introduced into the bloodstream and the bubbles are already used to improve contrast in medical imaging. The technique has advantages over light stimulation, not least the ability of ultrasound to penetrate through tissues, as demonstrated by its common use in pregnancy scans.
The impact of such research, if eventually translated into mammalian systems, would be significant. One of the research’s authors, Stuart Ibsen, has stated: “This could be a big advantage when you want to stimulate a region deep in the brain.”
However, the scientific community advises against getting ahead of ourselves. Michael Hausser, Professor of Neuroscience at UCL, commented: ““I would urge extreme caution about extrapolating this work to other species – especially mice or humans”.
Currently, the researchers are studying a very simplistic nervous system model, containing only 302 neurons, whereas humans have a whopping 86 billion neurons and 85 billion non-neural support cells. Further to this, the worms used are approximately 1mm in length with relatively exposed circuitry; the use of ultrasound may therefore not be comparable. It is clear that this research has a long way to go before getting anywhere close to human applications, but as a conceptual idea, it’s a remarkable new starting point.