Molecular biologists from the Institute of Bioorganical Chemistry together with neuroscientists from the Institute of Higher Nervous Activity and Neurophysiology and physicists from the M.V. Lomonosov's Moscow State University developed a novel technology of nerve cells stimulation by the infra-red light followed by genetic embedding of snake's thermoreceptor proteins to the mammal neurons. The results were published in the Nature Communications and uncovered a possibility of non-invasively stimulate the neural networks of any animals and control the activity of any other cells types in the living systems.
Scientists were longer interested in how they can drive single neurons. Particularly, In 1979 Fransis Crick who discovered the DNA stucture together with James Wotson proposed that the main challenge in neurobiology is creating methods that would allow to stimulate certain type of cells remaining any other cell types being insensitive to the light. The practical implementation of his idea was only in 2005 where the research group from Stanford University directed by Karl Disserot could excite nerve cells by light radiation. Such a method was named optogenetics (mix of optics and genetics).
The neurons gain the sensitivity to light because of light-sensitive receptor proteins which aid living organisms to navigate in space in the wild nature. Such proteins can be divided into several classes depending on the type of physical impact. Hence, the light signals are detected by rodopsines and photopsines while temperature alterations are recorded by TRP (Transient Receptor Potential) family receptors. The last one are responsible for why we feel warm and cold objects as well as taste of spicy food and mentol "cold". Thermoreceptors were based to the thermogenetics method allowing drive single neurons by the long-wave infra-red light which penentrate to the tissues very deep.
Scientists from the M.M. Shemyakin's and Y.A. Ovchinnikov's Institute of Bioorganic Chemistry, RAS, Institute of Higher Nervous Activity, RAS, M.V. Lomonosov's Moscow State University used in their research thermoreceptors TRPA1 of snakes as highly-sensitive thermoreceptor proteins that are responsible for thermovision: an ability of snakes to "see" warn objects at distance. This helps animals to orient in space and hunter in the dark.
The first part of experiments were done on the mice nerve cells in-vitro. The neurons were locally radiated by the infrared light from the optofiber laser while their activation were registered electrophysiologically by measuring ion flux through the membrane.
"We were able to measure dynamics of neural response to very little temperature changes on which the neurons usually don't response", - explains Evgeny Nikitin, a leader of Neurophotonics group. The data revealed proved an ability of selective control of neural activity of cells with embedded snake's thermoreceptors.
The study included not only biological but also physical constituent. In order to provide thermogenetic stimulation this is important to warm living tissue to a given temperature not exceeded 1-2 degrees. Insufficient warming can't activate the neurons while excessive warming will result to cell overheat and death. Physicists of MSU governed by Alexey Zheltikov developed a method of local detection of temperature by means of quantum effects in diamond microparticles with specific defects of their crystal cell. Such a diamond being placed to the end of the optofiber can measure temperature of heating specimen with a great precise.
The thermogenetics method uncovers wide perspectives in usage in the following developments. First, the infra-red light penentrates to the tissue deeper. Hence, there will be an ability to stimulate deeper brain regions. Moreover, not only infre-red light but also high-focused microwaves and high-power magnets were possible. Next, thermogenetics has a great advantage when dealing with small model animals such as snails, fish fries and fruit flies. In classical optogenetic experiments animals see blue light used for sell activation and worry about it. The infrared light is invisible for them so we can cope with side reactions on bright light. Finally, the revealed molecular and technical instumentation is useful for activation the other cell type in the organism. All together this will result to emergency of new methods to therapeutic stimulation and supression of functions of different cells in the organisms. Optogenetics make only first steps in this region, thermogenetics will join to it.
Reference
P.M. Balaban Molecular Mechanisms of Memory Modification. Zhurnal Vysshei Nervnoi Deiatelnosti. 2017. V. 67. N. 2. P. 131-140.
Ermakova Y.G., Lanin A.A., Fedotov I.V., Roschchin M., Kelmanson D.K., Bogdanova Y.A., Shokhina A.G., Bilan D.S., Staroverov D.B., Balaban P.M., Fedorov A.B., Sidorov-Biryukov D.A., Nikitin E.S., Zheltikov A.M., Belousov V.V. Thermogenetic neurostimulation with genetic-cell resolution. Nature Communications. 2017. V. 8. 153562. DOI: 10.1038/ncomms15362