The brain may be one of the most fascinating organs in the human body, and yet, we still haven’t fully unlocked its mysteries. However, with the advent of optogenetics, scientists now have a better chance of understanding how the brain works.
What is Optogenetics and How Does It Work?
Optogenetics is a biological technique that uses light and genetic engineering to control the activities of the cells in the brain (neurons). Interestingly enough, it accomplishes its intended purpose by altering the electric state of the neuron with remarkable precision, even in freely moving animals. Here’s how it works:
In this method, the neurons are first genetically modified by inserting a new piece of code (e.g. through the use of viral vector targeting systems or Cre-recombinase-based mouse lines) to express light-sensitive transmembrane proteins (opsins). Opsins are currently the most powerful and most widely used actuators used to modify the activity of the cell upon exposure to light of the correct frequency.
There are two classes of naturally-occurring opsins: microbial opsins (Type I) and vertebrate opsins (Type II). Type I opsins are typically used by host microorganisms for navigation and to control intracellular concentrations of a variety of ions and the beating of the flagella, while Type II opsins are typically used for vision and circadian rhythm modulation. Some opsins have also been genetically engineered and synthesized to suit a variety of purpose.
Depending on which opsin is chosen for expression, the neurons will either be activated or inhibited, or their signaling pathways modulated upon exposure to precisely timed pulses of light. Some of the most commonly used light sources in these experiments include diode-pumped solid state lasers, optical fibers, and light-emitting diodes (LEDs).
Optogenetic sensors for calcium (GCaMPs), neurotransmitters, vesicular release, or membrane voltage are then used to record resulting neuronal activities. These help researchers determine whether the electrical activity produced the desired effect and the manner by which it was produced.
Importance and Implications
Optogenetics has opened up a whole new world for brain research. By using this method, we can finally figure out how the nervous system works, gain more insight on neurological and psychiatric diseases (including anxiety, depression, obsessive-compulsive disorder, social dysfunction, and drug addiction), and discover appropriate cures to restore or enhance brain functions. Optogenetic tools have also been used to study other cell types in the heart and retina.
Additionally, optogenetics has been applied to gain a better understanding of human behavior and physiology (e.g., movement, learning, memory, metabolism, blood pressure, sleep, and sensory processing) and the cellular activities associated with several medical conditions (e.g. chronic pain, epilepsy, Parkinson’s disease, and stroke).
Despite all the exciting possibilities, optogenetics may not be without ethical, legal, and social implications, especially when applied to humans. For example, one particular study successfully implanted a completely artificial memory in transgenic mice by training them to associate a certain odor (in this case, the smell of cherry blossoms) with a noxious foot shock.
The researchers then activated a certain receptor on the test animals’ olfactory sensory nerve cells through optogenetic light stimulation. Interestingly enough, the mice avoided the cherry blossom odor (since it has been associated with foot shock), even though they haven’t encountered this particular odor before. This only proves that memory can be transferred or artificially created by stimulating the electrical activity of specific neural circuits.
While memory manipulation may benefit people who are experiencing memory impairment or those who are suffering from post-traumatic stress disorder or chronic pain, the ethical issues on using the technology on humans remain. While it may still be a distant possibility, stringent measures should be instituted to ensure that such applications are approached ethically.
