By Akshaiyaa V S
And God said, “Let there be light”.
Figuratively, this bible verse points towards light as the foundation of life; the driving force behind our psyche. Bright light is always associated with joy and victory. But sometimes, the best ideas come only in subtle darkness. In this case, it was in the form of algae.
A Unicellular alga known as Chlamydomonas, produces proteins called opsins which can convert light into an electrical signal, thus activating cells on exposure to light. Ed Boyden, an American neuroscientist, discovered that inserting these proteins into the human brain can help solve psychiatric issues by either activating or deactivating the abnormal cell associated with it. As the name suggests, optogenetics combines light-sensitive proteins and genes to help cure such ailments.
Problems related to using drugs in psychiatry
Drugs used for psychiatric diseases such as schizophrenia not only affect the brain cells causing the disorder but also wipe out the healthy cells surrounding them, since the affected neurons are “bathed” in drugs, jeopardizing the brain as a whole. The cognitive abilities of people who use psychiatric drugs, as a result, diminishes. Also, the complexity of the drugs increases when you try to negate the side effects caused by it. Optogenetics evades this problem by focusing only on the affected cells, and by “turning off” the parts of the brain causing disorders.
How does the Optogenetic mechanism work?
A virus is modified with a light-sensitive gene present in the algae and injected into the affected neurons, which then distributes it throughout the cell, similar to solar panels on the rooftop of a house. This process requires precise knowledge of neurons and an understanding of the brain circuit mechanisms. Now isolated from the rest of the neurons, the affected portions can simply be “switched off” by flashing light over the brain, with the help of optical fibers connected to lasers. Viruses are tweaked for accuracy.
In a research conducted on mice, optogenetics helped isolate and “turn off” cells causing compulsive behavior. While the tests are successful in treating mice with OCD (Obsessive-Compulsive Disorder), further research is being done to use the technique on human as well, which are more complex.
Since optogenetics is all about genetically modifying neurons to create foreign proteins, reversing the process is impossible as of now.
What are the benefits of Optogenetic therapy in mental health?
Optogenetic therapy has helped solve major psychiatric issues by reacting suitably to each disease.
For instance: cellular excitation and autism are closely related. The major problem with autistic children is an increase in the number of cortical cells in the prefrontal cortex when compared others, leading to overstimulation. Optogenetic therapy helps slow down the stimulation process and consequently, stabilizes it.
Yet another example is the Parkinson’s disease, which is caused due to changes in the “basal ganglia” circuit in the brain. Placing optogenetic proteins in the circuit is proven to be extremely effective. The experiment was successful in rats, though it is yet to be tested on humans.
In case of epilepsy, the optogenetic protein shuts down the overexcited neuron by inhibiting its function, thereby stopping the seizure before major damage is done.
Optogenetic therapy might also help in managing schizophrenia, an abnormality in transmitting and processing information. It is caused by a scarcity of neocortical parvalbumin neurons causes an imbalance in the excitation of brain cells. Exciting the optogenetic protein can make up for the missing cells and help in balancing activity of those cells.
One of the most challenging optogenetic experiments was testing it on mice with OCD. The modified protein inhibited overstimulation of a particular neuron which, in turn, led to the overstimulation of another neuron. Its success was revolutionary as treating OCD otherwise involves heavy medication with undesirable side effects.
Experimenting optogenetics with depression and post-traumatic disorders is ineffective as there exists the problem of specification of the cells. But this is overcome by activating dopamine-rich cells, thereby stimulating the positive feelings like happiness.
Something might go awry
To control the neurons with light, genetic material must be added to every desired cell. While this is successful in the case of mice, it’s still being experimented for the human brain structuer. Also, the possibility of light scattering during treatment has not yet been considered. Certain ailments like schizophrenia cannot be tested completely as mice behave differently from humans.
Proper knowledge of the neural network is also necessary in order to successfully implement optogenetics since the modified protein cannot be altered. Also, while side effects have not been observed in mice, it is not necessary that it will be the same in the case of humans too; this raises a huge health concern.
Consent is yet another aspect important in the area of mental health. Activation of the Lateral amygdala, the locus of “fear memory storage” when subjected to an auditory stimulus, was found to forcefully initiate the feeling of fear in mice. Though this is only an experiment conducted on mice, it is alarming as similar experiments to control humans without their consent are also possible. But coming to think of it, the idea of activating brain cells is similar to the plotline of the Sci-fi movie, “Lucy”. It follows Lucy, the protagonist, who achieves 100% brain power due to a drug. Similarly, optogenetics might be able to activate powerful but inert regions of our brain, thus having unstudied consequences, for better or for worse.
How are they taking the research forward?
Recent studies are being conducted on monkeys rather than mice to check the reliability of the method on more complex brain structures. In some cases, though optogenetics doesn’t solve the abnormality in the neurons, it helps scientists learn more about the structure and functionalities of the brain.
In the future, we can expect optogenetic treatment methods to replace pacemakers and other supporting devices since it directly involves neurons, making it simpler to activate the damaged parts of our body, naturally healing it in the process.
Finally there would be light on our brains, both literally and figuratively.
Akshaiyaa V S is an analyst at Qrius.
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