Reaching New ‘Lights’: The Science of Optogenetics

Control your brain with light!

By Shifa Hussain

This pinkish-grey organ is said to be capable of creating more ideas which are equivalent to that of the atoms in the universe!

The human brain is the most complex part of the body, composed of about 86 billion neurons- which is about the number of stars in the milky way! Each neuron uses tiny electrical impulses and chemical signals to transmit information between different areas in the brain and nervous system.

Now, what if a neuron were able to work on command? What if you were able to control what a neuron did, and when?

This isn’t science fiction- it’s real! Scientists have been able to create a synthetic biological technique called ‘optogenetics’, to activate specific neurons or single celled creatures, to control the activity of neurons or other cell types with light.

First of all, how does a neuron transmit signals?

Certain pathways on a cell’s surface are called ion channels, which are somewhat like switches that start and stop electrical signals travelling down the cells. They’re activated when neurotransmitters- which are signalling molecules created by neurons- attach themselves to the receptors. This allows charged atoms or ions to move into the cells and generate an electrical current. This allows signals to be transmitted.

Channelrhodopsin is a cation channel. Cations have positive charges to them. Archaerhodopsin is an anion channel. They have negative charges.

Scientists had been trying to control the activity of ion channels for years, as this would have great potential for changing neuronal function- to understand, treat and potentially cure neurological conditions.

During the 1970’s, scientists Richard Henderson and Nigel Unwin from the Medical Research Council Laboratory of Molecular Biology (LMB) in Cambridge, discovered that a bacterium called Bacteriorhodopsin opened its ion channels in response to green light, due to a class of protein known as “opsins”.

It was discovered that opsin also exist in plants.

Algae are single celled organisms that have evolved to swim towards light. When blue light is shone on the eyespot of an algae cell, a channel opens and electrical signals are sent to allow the flagella to propel the algae towards sunlight.

Fig. 1 Illustration depicting light sensitive protein

If this light sensitive part of the algae were cloned and then was added into the neurons using genetic modification, those neurons could be made light sensitive as well, changing the behaviour of the animal!

Fig. 2 shows the process of opening and closing ion channels

However, the light used must be on the wavelength that a channelrhodopsin responds most optimally to- which is why blue light was used for the algae, while bacteriorhodopsin had green.

Scientists have been able to test this on mice and lab rats.

After genetically modifying the neurons in the mouse’s brain, fiber optic wires are fed through a hole in the skull and used to transmit micro-precise light pulses, which last just 0.001 seconds, directly to a specific group of cells.

Fig. 3 illustrates neurons communicating after light activation.

This triggers the ion channels to open, sending signals.

Patients who suffer from anxiety have abnormal communication between two parts of the amygdala, which is a cluster of cells located at the base of the brain. But it’s difficult to determine whether this is the cause or effect of the condition. It’s possible for optogenetics to be used to aim for the same pathway in a mouse and observe the results.

In an experiment called the ‘elevated plus maze’, which is two tunnels crossing over each other, is a well known anxiety test that measures how long the lab mouse takes at the closed portion of the arms compared to exploring the open portion.

Mice have evolved to prefer small, enclosed spaces like their burrows due to the safety it provides. However, they would have to venture out in the open to find food, water and mates, which would only happen if the animal is comfortable with the environment.

When the scientist turned the light on, the mouse’s behaviour changed immediately, exploring the arms of the maze. When the light was switched off, the mouse regained its previous, hesitant demeanor, receding to the closed off ends of the pathway.

After that breakthrough, it was confirmed that changing the activity of specific neural circuits through the use of optogenetics can trigger dramatic changes in the animal’s behaviour!

Currently, scientists are working to use this technology and apply it to humans so that neurodegenerative diseases may be neutralized!

Optogenetics has truly ‘shed some light’ on our understanding of the brain and behavior. It may someday be used as precision medicine to treat diseases more effectively.

REFERENCES

Candice, Lee. Lavoie, Andreanne. Liu, Jiashu. Chen, Simon X. Lui, Bao-hua. “Light Up the Brain: The Application of Optogenetics in Cell-Type Specific Dissection of Mouse Brain Circuits.” Frontiers. https://www.frontiersin.org/articles/10.3389/fncir.2020.00018/full, January 01, 0001.

Boyden, Edward. “Explained: Optogenetics.” YouTube, uploaded by Massachusetts Institute of Technology, 7 November 2013, https://www.youtube.com/watch?v=Nb07TLkJ3Ww

Tye, Kay M. “What investigating neural pathways can reveal about mental health”, Ted. https://www.ted.com/talks/kay_m_tye_what_investigating_neural_pathways_can_reveal_about_mental_health?language=en, October 2014.

Chin, Stefan. “Optogenetics: Using light to control your brain”, YouTube. https://www.youtube.com/watch?v=D_9rdj4SJrchttps://www.youtube.com/watch?v=D_9rdj4SJrc uploaded by SciShow, 1 March 2018.

Fig. 1, Fig. 2 and Fig. 3 illustrated by Shifa Hussain.