Optogenetics — Discovering How the Brain Works
The problem that neuroscientists have been facing is that they can’t study the brain cell by cell, neuron by neuron.
We know that the occipital lobe is used for vision, but we don’t exactly understand how the individual neurons contribute to the overall result of us functioning. What signals do my neurons fire when I type letters on my keyboard? What triggers me to think? What is my subconcious?
Electrical stimulation will stimulate all cells in that area without discrimination. Drugs are not specific enough and are too slow to respond to the millisecond timeframe of events in the brain.
This is what optogentics aims to solve and it’s basically a method of using light to turn cells or in this case neurons, on and off. Let’s unpack that.
What do I mean by turning cells on and off? Well if you think about neurons, they’re cells that take in electricity and outputs some amount of electricity to other neurons.
Now if we think about a light switch, when we flick the light switch, electricity flows into the switch and the light turns on. If we turn the switch off, the electricity stops, and the light turns off.
Similarly, with optogenetics, through certain mechanisms I’ll explain later, the neuron will either be triggered to activate and send electricity to other neurons or it will be deactivated and not send any electricity.
Why exactly is this so important?
Well, if we think about an equation of cells…
Cell 1 + Cell 2 + Cell 3 = Walking
We can deactivate one cell and see the output of the other 2 cells and reverse engineer what that first deactivated cell contributes. If we deactivate Cell 1 and see that Cell 2 and Cell 3 result in me not being able to walk in a straight line, then we can probably figure out what role Cell 1 plays.
Alright, now let’s get down to it and really figure out how we can activate and deactivate cells using just light.
Algae. Chlamydomonas reinhardtii. That’s the secret.
This particular species of algae conducts photosynthesis like all plant species do and in order to maximize the amount of energy it gets from photosynthesis, it wants as much light as possible. So it evolved a light sensitive patch where the cells are activated once light hits it and allows the algae to move towards the light.
Sound familiar? The cells are activated once light hits them which is what optogenetics is all about!
Scientists have been thinking about how we activate and deactivate cells using light since the 1980s, but it was only in the mid 2000s that we discovered optogenetics. The problem was that they couldn’t figure out how to get the cells to be regulated by light, but the funny part is that biologists had already been studying algae like this for a while. It was only until the mid 2000s that we made the connection.
Okay so now let us make the connection between algae and neurons.
The algal membrane contains light sensitive proteins called opsins that together form a transmembrane channel. This specific channel, called channelrhodopsin 2 (CHR2), in algae opens in response to blue light, resulting in calcium ions entering the cells and depolarizing the cell, letting it send off its charge/electricity to other cells alerting them to the light source. This in turn allows the algae to move towards the light.
We can also turn cells on and off independently off each other using, Halorhodopsin, an ion channel from Archaebacteria. It’s activated by a different wavelength and allows us to inhibit cell activity as opposed to activating it. Since it uses a different wavelength it won’t interfere with the CHR2 and won’t cause any problems for us.
Now with neurons, we can insert the light sensitive molecules, (CHR2), using a virus to recombine the DNA with both the CHR2 and the neurons. This would then allow us to have the same ability of activating cells using just blue light. Upon activation, the cell would change shape and allow negative ions to enter the cell, depolarizing it, and send off a signal!
And that’s the story of how we’re able to control cells using light!
Optogenetics Experiment — Controlling Fear
So scientists placed a mouse in environment 1 and then proceeded to play sounds of predators, and just try and scare the living daylights out of the mouse. The mouse was observed to be looking around anxiously and just generally frightened. Scientists recorded these observations.
A few days later they put the same mouse in environment 2. There were no sounds of predators, nothing that could scare the mouse. Then using optogenetics, they activated the specific cells that were activated during the mouse’s fear response in environment 1. And the mouse was observed to be looking around anxiously, breathing faster!
Even though there was nothing to be afraid of, we managed to activate the cells induced in the fear response of the mouse! That’s absolutely insane!
Applications — So What?
The most bewildering thing for me is that we have people suffering from depression, anxiety, PTSD, Parkinson’s, and we know that something is wrong and is causing pain to these people, but we have absolutely no idea what. We may know that depression is caused by deficiencies in people’s gut microbiomes that interact with the brain to cause depression, but how?
How can we even begin to start trying to help these people when we don’t even know what’s wrong?
It just doesn’t make sense. Optogenetics is the bridge that allows us to figure out what is wrong and then maybe even be instrumental in curing these diseases. Right now, we need wires to deliver the light to cells, but there are research papers about how we can get light to be produced internally within brains for activation of cells on a personal level.
A benefit of Halorhodopsin (deactivating cells) is that we can turn off pain. The cells that are activated by cells can be deactivated temporarily once we have acknowledged the pain. For example, once you have broken your arm and gone to the hospital, we don’t need to feel the pain anymore so we can just turn it off. This is also super helpful to patients with chronic pain disorders.
Optogenetics isn’t just for neurons either. It can be applied to any cell in the body. It can be used to control our heart beat to correct heart abnormalities. In addition, it could help us to give sight back to the blind by adding photosensitivity to their retinas.
Yet another application is with brain machine interfacing — the field that delves into how the brain and machine can directly interact and “talk” to one another. With a deeper understanding of how the brain works, we pave the way for brain machine interfaces and allow for machines to decode exactly what our thoughts mean, enabling us to control the physical world around us with only our thoughts!
Looking further into the future
Homo sapiens have been around for thousands and thousands of years and in that time we’ve evolved from being apes to being two legged hunter gatherers to being the most powerful organism.
But it’s only in the last few hundred years that we moved into cities. We haven’t had enough time to evolve and adapt to this new world. For example, in the past when we stumbled upon an apple tree, we would want to eat as much as possible before some other tribe came because we have no idea when our next meal will be. Nowadays, we are fortunate enough to have plenty of food and many of us don’t have to worry about our next meal.
But our bodies are still wired to consume high calorie, sugary meals. This is an example of how our brains haven’t had time to adapt to this world and the “rules” of this new world.
With newfound understanding from the world of optogenetics of how our brain works, we can start unravelling the mysteries of our brain and how it works. With this knowledge maybe in the future we’ll come at a point where we’ll be able to reorganize, rewire, reoptimize our brain to be better!
We’ll find better ways to process information and be able to hardwire this into our brain. This will be the next step in our evolution. Artificially evolving ourselves and our brains to catch up with the rapidly changing world.
Thinking about optogenetics and the potential of evolving our brain to be greater than anything we can imagine…
It’s absolutely amazing.
With optogenetics, we’ll be able to reoptimize the thing we understand the least, our brain, to work for us and allow us to be superhuman.
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