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Optogenetics: An Illuminating Tool with A Bright Future

Nearly everything we do requires our brain in some way. Eating a bagel? That uses your brain. Reading this article? That’s using your brain, too. All those questionable decisions you made in college? It may have felt like you weren’t using your brain, but you were. We’ve known for quite some time that the brain controls everything we do, but how the brain regulates our behavior is much less understood. In fact, an entire scientific discipline, neuroscience, is dedicated to unlocking these mysteries of the brain. Discoveries made in the neuroscience laboratory can then be transferred into a clinical setting where that knowledge can be used to develop new therapeutics. Countless concepts such as antidepressants, deep-brain stimulation, and cochlear implants have developed into viable treatment options thanks to a better understanding of brain function through neuroscience research.

Perhaps the best way to understand how the brain controls a behavior is by directly manipulating the activity of a specific part of the brain and observing how those changes subsequently affect behavior. Neuroscientists already have a number of tools at their disposal to do exactly that, but they are constantly developing newer, more-sophisticated techniques. More refined tools provide more precise control of the brain that ultimately yields greater insights. Among the latest and greatest technologies in the neuroscientist’s toolbox is a technique called optogenetics, which uses light to control neural activity, allowing researchers to control the brain as easily as flipping a switch.

To better understand optogenetics, it may be helpful to familiarize ourselves with how information travels through the brain. At the level of the individual neuron, information travels as an electrical current from one end of the neuron to the other. These “brain waves” are what electroencephalograms (EEGs) measure, and treatments like electroconvulsive therapy or deep-brain stimulation work by generating or disrupting these electrical signals. But the electrical currents coursing through your brain are not like the electricity found in a wall outlet, which relies on the movement of electrons. Instead, the electrical currents of the brain are due to the intricate flow of ions across a brain cell, and optogenetics takes advantage of this flow of ions to alter activity within the brain.

“To put it simply: optogenetics allows researchers to control brain activity with light. Since the brain controls behavior, scientists can use optogenetic manipulation of neuronal activity to shape behavior.”

Optogenetics involves light-reactive proteins; when light strikes these proteins, they open a channel that allows ions to flow across the cell, which ultimately either generates a new electrical signal or disrupts signals passing through. Researchers are able to insert these optogenetic proteins into the cells of a specific part of the brain, then surgically insert a fiber optic implant directly into the brain to deliver light to neurons expressing these optogenetic proteins. To put it simply: optogenetics allows researchers to control brain activity with light. Since the brain controls behavior, scientists can use optogenetic manipulation of neuronal activity to shape behavior. This is not science fiction. For over a decade, we have been able to use lasers to control the brain and influence behavior. Before we get out our pitchforks and torches, allow me to specify that research using optogenetics is being conducted on laboratory animals and is still a long way away from being widely used on humans. Nobody will be controlling your brain with lasers anytime soon.

Okay, controlling the brain with lasers is neat, but what can it show us about the brain? Scientists have used optogenetics to identify brain circuits that control feeding behavior. For example, suppressing activity in one feeding circuit with optogenetics disrupts eating even in hungry animals. Optogenetics has even been used to demonstrate how memories are stored in the brain. In a series of remarkable experiments, scientists were able to optogenetically stimulate specific collections of neurons to evoke a previous memory or even implant a false memory in mice! In the former study, researchers were able to isolate the neurons that were active when the mouse received an electrical shock, and when researchers optogenetically activated this ensemble of neurons the mice froze in fear (the same behavioral response they showed when originally shocked). In the latter study, researchers again were able to isolate neurons activated by a specific place, such as a mouse cage (setting A). Researchers then placed the mice in a new, distinct setting (setting B) and shocked the mice while stimulating the neurons from setting A. When these mice were placed back in setting A, they froze in fear as though they expected to be shocked, even though they never received an electrical shock in this specific location!

“Beyond its utility in the laboratory, optogenetics has great potential as a therapeutic tool in a clinical setting. One of the obvious uses of this technology is to treat certain types of blindness.”

That all seems neat (and maybe even a bit scary), but what can optogenetics do for me? Beyond its utility in the laboratory, optogenetics has great potential as a therapeutic tool in a clinical setting. One of the obvious uses of this technology is to treat certain types of blindness. Doctors hope to restore sight to these patients by inserting these light-reactive optogenetic proteins directly into the eye. Such applications would have the added benefit of being relatively less invasive.

Rather than requiring a fiber optic implant, light would be able to activate the optogenetic protein directly as it passes through the eye – just as normal vision works. Even now, clinical trials using optogenetics to treat blindness are already underway. More ambitious goals may even involve using it to curtail over-eating in an effort to combat obesity, similar to what has already been achieved in lab animals. It may even be possible to restore motor function in paralyzed individuals. Often in these cases, a severed spinal cord is no longer able to transmit motor signals from the brain to the arms or legs. Here, optogenetics could be used to bridge the connection across the break so that these signals will reach the limbs and allow them to move again. Given that the brain controls everything we do, the potential clinical applications of optogenetics are as diverse as they are exciting.

The civil rights activist Ella Baker once said, “Give light and people will find the way.” Given a few well-placed flashes of light, neuroscientists have found a way to control the brain and behavior with unparalleled precision. This advancement has launched a new era in neuroscience research marked by fantastic discoveries, but may hold even greater potential as a therapeutic tool used to treat a range of ailments. What started as a clever tool in the laboratory may provide a glimmer of hope for those with currently untreatable conditions.

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Intrigued? Learn more about this new technology from our partners at BrainFacts.Org. Let us know how you think optogenetics will impact our future, both in the field of neuroscience and in therapeutic settings, in the comments below!

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Symbolic illustration of optogenetics with a strand of DNA coming out of someone's cartoon brain and being examined by a magnifying glass. Designed by Alexa Erdogan.

— Written by Jeff Olney. Feature image designed by Alexa Erdogan.

References
  • Jennings, J. H., Rizzi, G., Stamatakis, A. M., Ung, R. L. & Stuber, G. D. The inhibitory circuit architecture of the lateral hypothalamus orchestrates feeding. Science 341, 1517–1521 (2013).
  • Liu, X. et al.Optogeneticstimulation of a hippocampal engram activates fear memory recall. Nature 484, 381–385 (2012).
  • Ramirez, S. et al. Creating a false memory in the hippocampus. Science 341, 387–391 (2013).
  • Bourzac, K. Texas Woman Is the First Person to Undergo Optogenetic Therapy – MIT Technology Review. MIT Technology Review(2016). at <https://www.technologyreview.com/s/601067/texas-woman-is-the-first-person-to-undergo-optogenetic-therapy/>

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Author(s)

  • Jeff is a postdoc at the University of Michigan where he researches the neuroscience of emotion. His experiments aim to better understand how specific brain systems become dysregulated in neuropsychiatric disorders (e.g. addiction, schizophrenia and depression). Jeff is also a member of the University of Michigan’s RELATE program (Researchers Expanding Lay-Audience Teaching and Engagement) - an organization that seeks to improve communication between scientists and the lay-public.

Jeff Olney

Jeff is a postdoc at the University of Michigan where he researches the neuroscience of emotion. His experiments aim to better understand how specific brain systems become dysregulated in neuropsychiatric disorders (e.g. addiction, schizophrenia and depression). Jeff is also a member of the University of Michigan’s RELATE program (Researchers Expanding Lay-Audience Teaching and Engagement) - an organization that seeks to improve communication between scientists and the lay-public.

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