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Summary -
This article talks about how technology combined with biology has led to the development of a revolutionary approach to control how brain cells communicate and their activation process. It also emphasises the utilization of this approach in the treatment of diseases.
From savagery to barbarism and finally, to our current state of civilisation, we have come a long way. Technology has changed our outlook on health, and many medical conditions are being researched upon with solutions expected to alleviate human suffering. We have all watched science fiction movies packed with high octane action and fictionalised depictions such as simulated reality, erasing memories from the brain or directing how the brain works. We still have a long way to go to achieve all that, but controlling how brain cells communicate is one of the feats made possible with the continuous progress in technology.
The fields of medicine and engineering have always been thought to be worlds apart. However, the technological advancements in engineering merged with biology have given rise to an approach of precisely directing and monitoring biological functions. This approach is named optogenetics.
Optogenetics combines genetic engineering with light. It utilises light-sensitive proteins called opsins, extracted from organisms such as algae. Scientists edit the genetic code of the nerve cell they want to study by inserting the genetic code for the opsins. For instance, the light of 450 nm wavelength (blue light) activates channelrhodopsin--2 (ChR2) derived from Chlamydomonas reinhardtii, which leads to neuron activation according to exposure to blue light. Essentially, the exposure to light of 450 nm wavelength opens up the membrane channels essential for regulating the movement of ions (1).
Neuroscientists introduce these opsins into the brain by taking advantage of the cell's genetic mechanism. First, the genetic construct containing opsin genes that would instruct the nerve cells to make these light-sensitive channels is synthesised. Then it is inserted into a virus so that it can be introduced into the cell. When the virus infects the cell, they will release the opsin gene containing genetic construct as well. Finally, scientists introduce the virus into a particular brain area by performing stereotaxic surgery. Stereotaxic surgery utilises the three-dimensional coordinates of the brain region.
Once injected, the virus infects the nerve cells and passes the opsin genes. The nerve cells then proceed to produce opsin channels. They can be stimulated with the light of a particular wavelength, either within a live organism (in vivo) or brain tissues (ex vivo). These channels allow brain researchers to manipulate the brain region through light stimulation. It all depends upon the type of opsin being expressed. Some opsins permit activation of brain regions, while others lead to inhibition. It depends on the type of ions the channel lets in.
(A) The design of a system to introduce the genetic material containing the opsin into cells for protein expression such as application of an Adeno-Associated-Virus (B) Application of light emitting instruments (Pama E.A. Claudia, Colzato Lorenza, Hommel Bernhard, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons)
For instance, an opsin that permits inflow of negative ions like chloride ions into the cell would lead to inhibition, as the chloride ions will lead to the membrane potential becoming even more negative and move the membrane potential away from the threshold so that nerve cells or neurons cannot fire an action potential. However, the movement of positive ions like sodium ions into the channel leads to membrane potential reaching the threshold and allowing neurons to fire an action potential.
As each brain area has a specific function, these manipulations enable researchers to study how brain regions communicate, and how stimulation and inhibition of specific brain regions contribute to disease development. With such a colossal discovery comes a pretty expected question. Is the brain going to be affected, or is the procedure invasive and damaging? The answer to this is no. The optogenetic device produces high-intensity light to stimulate the brain with minimal invasion (2).
The research in optogenetics has been proven promising in letting scientists gain further insights into the brain. Optogenetics is expected to have a significant role in pain-free therapies for depression, addiction and other diseases by specifically targeting neurons. It will also benefit humankind by providing wisdom into dysfunctions of brain regions influencing other regions and their combined role in brain diseases.
References
1. Joshi, J., Rubart, M., & Zhu, W. (2020). Optogenetics: Background, Methodological Advances and Potential Applications for Cardiovascular Research and Medicine. Frontiers In Bioengineering And Biotechnology, 7. doi: 10.3389/fbioe.2019.00466
2. J. Ausra et al., “Wireless, battery-free, subdermally implantable platforms for transcranial and long-range optogenetics in freely moving animals.,” Proc. Natl. Acad. Sci. U. S. A., vol. 118, no. 30, Jul. 2021, doi: 10.1073/pnas.2025775118.
About the Author
Himanshi Yadav has recently completed Masters in Zoology with a specialization in Molecular Endocrinology and Reproduction from Miranda House, University of Delhi. She aspires to research and delve deep into Neuroscience and Cancer Biology. Her other fields of interest include Public health. She is keen on broadening the horizons of how science is being communicated and actively advocates for gender equality in STEM, inclusivity, and mental health awareness.
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