This Emerging Technology Can Control The Brain Using Light and Genetic Engineering
An Introduction to Optogenetics
The human brain is an incredibly intricate system with approximately 86 billion neurons. It is at the center of everything we say, think, and do, assisting us as we perform everyday tasks in addition to functions we don’t have to think twice about. The capabilities of the brain are truly incredible, and its ability to perform many different functions at once is amazing. However, problems can occur in the brain as well, often manifesting themselves in the form of malignant tumors or neurological (brain based) disorders. Some brain based disorders are based in too much activity between certain brain regions (such as anxiety). Others occur when there isn’t enough activity between regions, or when the performance of certain neurons deteriorates (such as Alzheimer’s).
These conditions can be very damaging to patients who have them, and deteriorate the quality of their lives as well as their capabilities. In the past this has been addressed with solutions such as medication, electrical nerve stimulation, and therapy. These solutions are sometimes effective, but often times were found to be either ineffective, decreasingly effective over time, only temporarily effective, or imprecise. Additionally, neuroscientists are still yet to achieve a complete thorough map of the human brain and its neuronal connections (see my article on connectomics for more details!) which makes it challenging to improve upon these methods.
With new developments in neuroscience and technology (neurotech), scientists are in the process of developing a unique new tool which can provide new information on the brain’s connections and how signals travel throughout the brain while simultaneously acting as an effective, efficient, and consistent treatment for all sorts of brain based disorders. That approach is called optogenetics, and it has the potential to completely revolutionize the future of neuroscience.
Before we dive into optogenetics, here’s a high level overview of how brains are structured and how they work.
The brain can be divided up into sections in a variety of ways but at the smallest level it is made up of neurons, the specialized cells which make up the nervous system. They pass information by firing electrical impulses across synapses, which form pathways between neurons. The average neuron has around one thousand synapses, so information is able to spread quickly to lots of different places. The aspect of this system that is significant to optogenetics is the way neurons communicate using the electrical and chemical impulses. These impulses are known as action potentials.
There are four parts of a neuron: the dendrite, the cell body, the axon, and the axon terminal. Signals from other neurons are received by the dendrite, and are only passed on to the rest of the cell (to the axon terminals which will then send the signal to other neurons) if the signal is strong enough. This is when the neuron fires.
Whether this signal is transmitted depends on charged particles called ions. Ions such as sodium and potassium are segregated between the inside and outside of a neuron. They can only travel in and out when ion channel receptors are opened up, acting as a bridge between the inside and outside. Ion channel receptors open when neurotransmitters latch on to their exterior, and then ions can move around. When the two types of ions mix up and are combined on the inside and outside, an action potential is generated and the cell fires.
Optogenetics is a tool which manipulates action potential to increase or decrease communication and firing between certain neuronal regions. It’s special because as opposed to tools like Deep Brain Stimulation which stimulate every neuron near the target area and aren’t precise at all, it can be applied to only specific groups of selected neurons.
So What Is Optogenetics?
Optogenetics is a neuroscientific technique that uses light and genetic engineering to control groups of neurons in the brain (hence the title of this article!). It works thanks to channelrhodopsin, a type of optic (relating to light) protein that was discovered because it naturally occurs in plants such as unicellular algae to assist it in the process of photosynthesis. When a certain color of light (for this specific type of opsin it’s blue light) shines down on the plant and reaches the channelrhodopsin, the protein generates an electrical signal that opened its cell’s ion channels to get them firing in order to photosynthesize.
It occured to scientists that if they harvested channelrhodopsins and put them in the brain, they would be able to control a neuron’s ion channels with light as well. They were able to find different variations of rhodopsins that are sensitive to different types of light, and with different functions as some were for the excitation of a neuron (increasing activity) while others were for inhibition (decreasing activity). Since they’re sensitive to different types of light, a person can even have multiple types of channelrhodopsin in their brain and use one without the other type having any reaction!
This can be effective for a whole group of neurons at once based on a physiological process that occurs naturally in the brain called neuromodulation. Neuromodulation is when one neuron uses chemicals to control a group of neurons. It occurs regularly in the brain, and can be used to the advantage of optogenetics in order to control more than a single neuron at one time.
Neurons are genetically modified by the surgical insertion of rhodopsins. An opsin construct called an Adeno Associated Viral (AAV) is injected into the brain through stereotaxic surgery. A Brain Computer Interface (BCI) which will deliver light as directed to control the rhodopsins is also inserted into the brain. Since rhodopsin is a naturally occurring protein, the brain is able to accept it consistently.
Once the genetic modification is performed, optogenetics can be performed at any time. The name optogenetics is derived from the combination of optics (because light and opsins are the tools being used) and genetics (because of the genetic engineering needed in order to achieve this).
When optogenetics is performed, targeted light of a specific color will be shone on a certain brain region. The genetically modified neurons in that area will then have a reaction and either increase or decrease their level of activity accordingly. Other types of opsins which aren’t sensitive to that color of light will have no reaction, even if the light is applied to them. This is very helpful, because optogenetics can be utilized for multiple of its many different functions in one person without them affecting each other.
While optogenetics as a technique is still in the mice trials stage of its development, advancements specifically in German labs over the past five years have been massive and suggested it could be used on humans in as soon as five years.
What Can Optogenetics Be Used For?
Currently, there are two main buckets of brain based optogenetic applications: research to understand how information spreads, and treatment for medical conditions.
The first way in which optogenetics can be utilized is as a research tool to gain understanding about specific synaptic connections in the brain and the spread of information within them. By stimulating a specific neuron or group of neurons to fire, scientists can see how information spreads specifically from that neuron by watching where the electrical impulse is sent to and how it ripples out as those neurons in turn spread the impulse. This adds to our understanding of how neurons spread information, and it also contributes to our ability to map each specific neuron and synaptic connection. These accomplishments work towards the bigger goal of having a complete map of the brain at the neuronal level.
This is very challenging to do with other electric stimulation techniques, as it’s hard to follow the process of one specific neuron when so many nearby ones are also activated at the exact same time. By using the specific stimulation capabilities of optogenetics, scientists are able to follow one neuron in a much easier way. This helps get us closer to a complete map of neurons and their synaptic connections, as well as understanding the strength or significance of each.
As for medical applications, optogenetics is being tested for a variety of medical conditions but largely those which have had successful applications of Deep Brain Stimulation. Although the precision and specific details of the techniques are the same, the high level concepts are similar which means conditions which DBS has treated can likely be treated by optogenetics even better. This includes many types of conditions: neurodegenerative conditions such as Parkinson’s, psychiatric conditions such as Generalized Anxiety, and neurodevelopmental conditions such as Autism.
Especially based on the fact that optogenetics is still in earlier stages of its development, the research based utilization of the technique is likely to be the main way optogenetics is used for for a little while. Not only is it a simpler concept, but it also requires less commercialization and widespread use of optogenetics devices. That said, many experiments are still being conducted to look into optogenetics as a tool for brain based conditions as this has the potential to be a very successful market both for helping people and making profit.
But wait a minute, that’s not all…
Optogenetics is a technique used to manipulate neurons. When faced with the word neuron, most people associate the term with the nerve cells in the brain. However, there are nerves all throughout the body. And the cells that those nerves are made up of are still neurons as well. So what does this mean in terms of optogenetics?
This means that other parts of the body within the nervous system can also have optogenetic applications! Another part of the body which has been experimented with for many optogenetic use cases is the heart. There are approximately 40,000 neurons in the heart, which means there’s plenty of neuronal material to work with. Heart based optogenetic applications include for cardiac pacing, resynchronization, arrhythmia termination, etc. The methods used to activate these neurons are different (such as light-induced dimerisation and photocaging), but the general principles are the same. So far the brain has been the most popular for optogenetic applications based on amount of use cases and efficacy rates, but in the future this is also an interesting and potentially helpful application of the technology.
Ethical Concerns of Optogenetics
Given that optogenetics requires invasive brain computer interface technology and is often referenced as “modern day mind control”, ethical concerns have definitely arisen throughout this field.
Invasive brain computer interfaces alone have a large number of ethical concerns, many of them centering around a fear that the machine would record personal data other than what it was specifically tasked to record, and export the data to an external computer or another BCI through a BBI (Brain to Brain Interface). Realistically speaking, the probability of this is fairly low. BCIs are yet to achieve any conscious state, and for them to take readings on a separate type of data then interpret it and export it seems unlikely as well. This concern is largely just stemming from the social stigma of emerging technologies with invasive properties.
However, there’s an entirely new set of similar concerns once the aspect of not just reading but also controlling the brain comes into play. These concerns are largely along the lines of the BCI controlling the person’s brain without their consent or in a manner other than what and when they intended to. The probability of this occurrence is similarly low unless the technology were to have some kind of malfunction which is also fairly uncommon. This is another example of stigma and societal norms creating apprehension around a technology as opposed to scientific facts or data.
Conclusion
Although it’s yet to be approved for human use, optogenetics has proven to have a variety of useful applications throughout the field of neuroscience. The pros of this technique seem to outway the cons and apprehensions, and recent advancements suggest that optogenetics could become a mainstream medical technique sooner rather than later.
In the future, optogenetics will likely have unique applications that work more precisely and effectively than current models such as Deep Brain Stimulation or medications. A little more research and testing is the only thing standing in the way between optogenetics and a future full of patients with brain based disorders receiving more advanced and successful treatments.
Key Takeaways
- Optogenetics is a neuroscientific technique which uses light and genetic engineering to manipulate neurons in the brain.
- The technique works because of two key neuroscientific principles: action potential (the mixing of charged ions inside and outside of a neuron’s exterior which cause it to fire or attachment of a neurostimulator to an ion channel receptor) and neuromodulation (a neuron using chemicals to control other groups of similar neurons).
- To set up optogenetics, a person must receive a surgical injection of rhodopsins (a popular kind being channelrhodopsin 2 which is found in algae) and have an invasive BCI implanted into their brain which will shine colored light onto neurons as directed.
- In the brain, the two main purposes for which optogenetics is used are learning about the brain’s connections and treating neurological conditions. Optogenetics also can have applications outside the brain in areas such as the heart.
- There are many ethical concerns surrounding invasive BCIs and controlling the brain, largely surrounding if functions were to be performed using either of these tools without a person’s knowledge or consent.
- Optogenetics is super cool and could have huge implications in the future of neuroscience and medicine!
Bonus Content
If you’re super interested or intrigued, here’s a company or two working in this space! I didn’t put them in the bulk of the article because they’re largely just for selling optogenetic experiment equipment since optogenetics isn’t allowed to be used for humans yet, but they’re still cool so if you made it this far check them out!
Thank you for reading my article, I hope you enjoyed it! My name is Raina Bornstein, I’m 15 years old, and I’m passionate about branches of neuroscience and neurological conditions. I’d love to connect on LinkedIn, or you can reach out to me at rainabornstein@gmail.com to talk or collaborate. I can’t wait to hear from you!
