Qué es la optogenética

What is optogenetics?


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By Dr. Pablo Barrecheguren

Of all the techniques developed in neuroscience over the last few years, optogenetics is probably the one that has most quickly become standardized as a work tool in laboratories. Its use is such that striking preclinical results are already starting to be show up. For example, its use as a therapy in the treatment of vision problems with a neurological base is currently being analyzed and, following with the senses, systems have already been developed in rodents that allow the recovery of part of the hearing using this type of technology as a possible alternative to the current cloquear implants. Although preclinical and modest, these are great results if we consider the short history using this technique but… exactly what is optogenetics?

What exactly is optogenetics?

Optogenetics is based on the use of light-sensitive ion (opsin) channels and pumps for the activation or inhibition of neurons, which allows in vivo manipulation of neuronal activity. However, it must be borne in mind that the presence of opsins is achieved through genetic engineering, being able to apply two different variants:

  1. Injection of viral vectors in adult organisms. In this case viral particles are generated that carry the opsins, the viruses are injected directly in the area of the brain where we want to apply optogenetics, the viruses infect the neurons and these begin to produce opsins.
  2. Direct creation of genetically modified animals that express opsins in certain areas of the brain or injection of viral vectors in utero into the brain of model organisms.

Depending on the field of research, one strategy or another is used in a model organism, which are generally mice. But in any case, the result is that we have a living being with opsins in its neurons. As a consequence of this, if these neurons are stimulated with light, the opsins will react to it generating an activation or inhibition of the neurons depending on the modifications we have made. And since it is possible to be quite specific when choosing which neurons express opsin and which do not, the result is that we can regulate the activity of specific neuronal pathways at will.

This is key to identifying the function of each neural network. For example, if we suspect that the activation of neurons increases appetite, then we can generate a mouse that has opsins in those neurons, stimulate those cells with light and see if the mouse ingests more calories. What’s more, the system literally works like a switch, so we can turn those neurons on or off whenever we want while we watch how the animal’s behavior changes, or doesn’t change, in real time. This has made optogenetics the most powerful tool for behavioral studies, but its potential is also in the study of brain development as we can cause changes in neuronal activity and then analyze whether or not that alters the development of the nervous system.

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Challenges of optogenetics

Even so, it is always important to remember that it is still basic biomedical research which has to overcome many challenges before it can be used in clinical settings. These are two of the main obstacles:

  1. It is usually possible to stimulate cells with light by implanting an intracranial device. This, although surgically possible, is a very important factor to bear in mind if we are talking about a possible use in human beings.
  2. For the technique to work it is necessary to genetically manipulate the organism. Nowadays it is already possible to create non-human transgenic primates, although they are extremely rare and their use is much more complex than that of other model organisms. But even when technical problems are solved, this will not eliminate the ethical conflict of having to use genetic engineering on human beings in order to biomedically apply optogenetics.

It is clear that the challenges, both technical and moral, presented by optogenetics are comparable to its great potential in the field of neuroscience, so it is a technique that must be followed with special interest over the next few years.

References

  • Deubner, J., Coulon, P., & Diester, I. (2019). Optogenetic approaches to study the mammalian brain. Current Opinion in Structural Biology, 57(1), 157–163.
  • Galvan, A., Stauffer, W. R., Acker, L., El-Shamayleh, Y., Inoue, K., Ohayon, S., & Schmid, M. C. (2017). Nonhuman Primate Optogenetics: Recent Advances and Future Directions. The Journal of Neuroscience, 37(45), 10894–10903.
  • Keppeler, D., Vogl, C., Dieter, A., Moser, T., Huet, A., Jeschke, M., … Duque-Afonso, C. J. (2018). Optogenetic stimulation of cochlear neurons activates the auditory pathway and restores auditory-driven behavior in deaf adult gerbils. Science Translational Medicine, 10(449), eaao0540.
  • Roska, B., & Sahel, J.-A. (2018). Restoring vision. Nature, 557, 359-367.

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