Sonogenetics is a new physiological technique involving ultrasound, to manipulate the neurons. The research team led by Prof. Sreekanth H. Chalasani at the Salk Institute for Biological Studies genetically modified the nervous system of Nematode worms (C. elegans) to control the brain using bursts of sound waves.
The concept of Sonogenetics is similar to Optogenetics, which uses light to switch neurons on and off. However, the major limitation of Optogenetics is that it is hard to get the light deep into the brain, and the light would scatter once it hits opaque tissues. On the other hand, Sonogenetics uses low-frequency ultrasound which can travel throughout the body without scattering or any loss of signal. Lastly, Optogenetics requires an invasive surgery in mammals, but Sonogenetics is non-invasive.
Initially, the genetically modified worms did not react to ultrasound, but they started reacting when they were surrounded by microscopic bubbles or microbubbles. The ultrasound wave, when focused on the head of the worm, made it move in a reverse direction. The ultrasound acted on a structure called TRP-4 ion channels, a pore forming subunit of mechanotransduction sensitive to low pressure ultrasound. C. elegans use these TRP-4 channel embedded neurons to sense when their bodies are stretching, and when these worms stretch, these channels open up in order to influx calcium. When the animal is exposed to the ultrasound, the TRP-4 channels open and activate the cells they are attached to. The sound waves are amplified by the microbubble and transmitted into the worms, and in turn switch on the modified motor neurons.
When the researchers targeted the TRP-4 channels with ultrasound, they were able to stimulate the movement of the worm. The researchers also targeted another sensory neuron known as PVD neurons. PVD neurons are multidendritic nociceptors which respond to harsh touch and cold temperatures. When these neurons were stimulated using ultrasound, there was a reduced change of directions in the animals. Sonogenetics has also been applied to neurons which are deeply located in the worm, and it has been shown that the neurons lit up when they were stimulated with sound using calcium imaging.
Currently, the technique is being adapted for use in rodents, as they are a common model organism to study the nervous system. Rodents might or might not require the microbubble to amplify the sound waves. But in case they require the microbubble, they can be injected into the blood stream, and are expected to cross the blood-brain barrier. If it could be done in mice, then researchers can target different brain regions multiple group of neurons at the same time and non-invasively.
Currently, deep brain stimulation (DBS), an invasive procedure, is used to treat motor symptoms of Parkinson’s disease (PD). In the near future, it might be possible to use Sonogenetics to treat such neurological disorders. For this to happen, the most important consideration would be to observe if microbubbles are necessary for amplification, or if there are other methods to amplify the sound waves. In the near future, Sonogenetics might be used to activate different brain regions including the deep brain structures, and this technique has great potential in clinical applications.
- Ibsen, S. et al. 2015. Sonogenetics is a non-invasive approach to activating neurons in Caenorhabditis elegans. Nature Communications, 6. doi:10.1038/ncomms9264
Chinmaya Sadangi, PhD