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Optogenetics
6
The Application of Genetics
By Andrew Mao
What is it?
Optogenetics takes advantage of genetically engineering to modify neurons into providing a response to light.
It allows for humans to artifically stimulate/fire a specific neuron to observe its effects in the brain.
Optogenetics
The Race to Discover Optogenetics
The History
In 2004, the neuroscience community was racing to find a way to apply channelrhodopsin-2 to brain cells.
Optogenetic's discovery was commonly credited to Ed Boyden from MIT and Karl Deisseroth from Standford. Their discovery of optogenetics was in 2005 shortly after the first molecular description of channelrhodopsin-2 was released in 2003.
Boyden and Deisseroth discovered optogenetics when they shined precise milisecond durations of light onto neurons affected by channelrhodopsin-2. They saw consistent neuronal spiking whenever the light was shown.
However, Zhuo-Hua Pan at Wayne State University is the lesser known scientist who was believed to have discovered optogenetics 6 months prior to Deisseroth and Boyden. He did this when he was testing channelrhodopsin in lab cultured ganglion cells and they became eletrically active when shone on with light.
Advantages
Optogenetics can help us learn how our brains work. It can let us see how our brains function when we turn off specific neurons.
Some success has been seen in treating neurological disorders in mice with the goal of treating humans in the future.
These include:
- Parkinsons
- Addiction
- Depression
- Schizophrenia
- Autism
- PTSD
The ability to temporarily turn off neurons can possibly help treat seizures, where all the neurons are firing at once.
Advantages
Disadvantages & Ethical Concerns
Due to optogenetics closely involing the brain, modifications result in permanent change to the host's nervous system. Therefore, damage is also permanent and can have major effects on a patient.
The introduction of channelrhodopsin to a neuron is permanent and long term effects are unknown.
Furthermore, the long term effects of shining light onto the brain are also still unknown.
Fairness to who is subjected to such trials also remains in debate.
The Uses
Optogenetics in Practice
- The main concept of optogenetics revolves around a protein found in green alga. These proteins are known as opsins but more specifically channelrhodopsin-2.
- When channelrhodopsin-2 is created in a cell, it allows for ions to pass across the membrane when exposed to blue light and thus creating electrical potential.
- For neurons to create these proteins, they first need to be genetically engineered to adapt to do so
- This can be done by injecting opsin DNA into neurons via a vector, namely through harmless viruses
- Viruses allow us to accurately target certain neurons
- Viruses will inject the opsin DNA into the cell and die, causing no harm but directly injecting the opsin DNA into the nucleus
- Once the opsin DNA has embedded itself into a neuron, the neuron will "read" this DNA and immediately begin the production of opsins
- Opsin proteins in neurons will then be found all around the surface of the neuron
- Optical fibres are implanted into the brains of the specimen, to flash light onto the neurons
- When these opsins are subjected to blue light, they "open up" allowing ions to enter the cell due to the imbalance of ions within and outside the cell.
- This intake of ions artificially fires the neuron, sending out an electrical signal.
Diagram of a Stimulated Neuron
Opened Opsins
Neuron Firing (Electrical Charge)
Blue Light
Interesting Facts
- Different kinds of opsins respond to different colours!
- Experimental trails of optogenetic treatment in HUMANS for blindness are in progress
- The implementation of opsins in the eyes of blind mice have shown to help them regain a slight sense of sight
Bibliographies
Adams, A. (2020). Optogenetics earns Stanford professor Karl Deisseroth the Keio prize in medicine. Stanford News. https://news.stanford.edu/features/2014/optogenetics/
Boyden, E. (2011, March). A light switch for neurons [Video]. TED: Ideas worth spreading. https://www.ted.com/talks/ed_boyden_a_light_switch_for_neurons
Boyden, E. S. (2011, November 30). Optogenetics. Dana Foundation. https://www.dana.org/article/optogenetics/
Grens, K. (2016, September 1). The history of Optogenetics revised. The Scientist Magazine®. https://www.the-scientist.com/the-nutshell/the-history-of-optogenetics-revised-32910
Lim, D. H., & LeDue, J. (2017, September 20). What is Optogenetics and how can we use it to discover more about the brain?. Frontiers for Young Minds. https://kids.frontiersin.org/article/10.3389/frym.2017.00051
Millisecond-timescale, genetically targeted optical control of neural activity. (n.d.). Nature Neuroscience. https://www.nature.com/articles/nn1525
MIT McGovern Institute, Pryor, J., Jennings, C., Sputnik Animation, & Boyden, E. (2011, November 30). [3D Rendering]. Dana Foundation. https://www.dana.org/wp-content/uploads/2019/08/optogenetics-cerebrum-nov-2011.jpg
Nagel, G., Szellas, T., Huhn, W., Kateriya, S., Adeishvili, N., Berthold, P., Ollig, D., Hegemann, P., & Bamberg, E. (2003, November 25). Channelrhodopsin-2, a directly light-gated cation-selective membrane channel. PNAS. https://www.pnas.org/content/100/24/13940.long
Schoonover, C. E., & Rabinowitz, A. (2011, May 17). Control desk for the neural switchboard. The New York Times - Breaking News, World News & Multimedia. https://www.nytimes.com/2011/05/17/science/17optics.html
More
More Bibliographies
Boyden, E., Zhang, F., Bamberg, E. et al. Millisecond-timescale, genetically targeted optical control of neural activity. Nat Neurosci 8, 1263–1268 (2005). https://doi.org/10.1038/nn1525
Vlasits, A. (2016, September 7). He may be the rightful inventor of neuroscience’s biggest breakthrough in decades. But you’ve never heard of him. STAT. https://www.statnews.com/2016/09/01/optogenetics/
Frederic Gilbert, Alexander R. Harris & Robert M. I. Kapsa (2014) Controlling Brain Cells With Light: Ethical Considerations for Optogenetic Clinical Trials, AJOB Neuroscience, 5:3, 3-11, DOI: 10.1080/21507740.2014.911213
Gilbert, F., Harris, A. R., & Kapsa, R. M. (2014, June 13). Controlling brain cells with light: Ethical considerations for Optogenetic clinical trials. Taylor & Francis. https://www.tandfonline.com/doi/abs/10.1080/21507740.2014.911213
Stanford. (2011, May 16). [Photograph]. The New York Times. https://www.nytimes.com/2011/05/17/science/17optics.html