Optogenetic Tools Enlighten Brain Research

Transgenic rat with LED light
Transgenic rat with LED lightGrad student Remington Rice
Grad student Remington RiceTracking the animal's behavior
Tracking the animal's behavior

Optogenetic tools, which allow scientists to control neurons in the brain with bursts of light, provide a powerful new way to study the brain. These relatively recent innovations offer greater precision in targeting specific neurotransmitters responsible for behavior than traditional methods such as electrode stimulation. At the urging of a graduate student, Northern Michigan University’s neuroscience program has acquired the cutting-edge technology and genetically modified animals required to conduct research typically reserved for larger institutions.

Adam Prus, NMU psychology professor, said the transgenic animals carry light-sensitive proteins capable of activating or deactivating neurons with a pinpoint accuracy that was not achievable until recently. The NMU project focuses on dopamine neurons. If researchers can more closely link dopamine to neurological disorders, Prus said it could lead to a more optimal pharmacological strategy for treating humans with medications that target those specific types of neurons. The techniques themselves might even be used in humans to treat certain neurological disorders, such as Parkinson’s or depression.

“Some people have resorted to surgical options, like [actor] Michael J. Fox did for his Parkinson’s,” Prus said. “He tried deep brain stimulation surgery, in which an electrode is implanted and stimulated to alleviate the symptoms. The procedure doesn’t work in all cases and it isn’t permanent. It might be that in the future, one could use optogenetic techniques as real treatment strategies in humans, perhaps better than brain stimulation approaches used today.” 

NMU graduate student Remington Rice educated himself on recent technology developments in the field and successfully lobbied NMU to purchase the animals and supplemental equipment required to complete his related master’s degree project. Another grad student and five undergraduates also work in the psychology lab.

Through a minimally invasive surgical procedure, Rice implants optical fibers into the transgenic animals’ neurons that have been modified with light-sensitive proteins. Blue LED lights are connected to the fibers and the light pulses through the fibers to the brain. NMU researchers put the animals in an open-field enclosure with a video-tracking apparatus connected to a computer. They monitor the animals’ behavior when the dopamine neurons are activated, turned off, or impacted by medication, then compare the results with a control group of non-transgenic or “wild-type” rats to determine if the proteins played a role.

“We can visually track their movements, from where they traveled to their velocity to how close they got to the walls, and all sorts of behaviors,” Rice said. “The expectation is that they’ll be more active with increased dopamine activity, to a certain point. We also record body temperature, which can increase when dopamine production is elevated. We can measure the physiological response to what we are doing to the neurons. All of this leads to research questions that can open new lines of investigation.”

While optogenetic tools are not currently authorized for human use, Rice said he is motivated by the knowledge gained with this technique and its potential applications. If bursts of light can be used to fire up surviving neurons in degenerative diseases, as in Parkinson’s, there might also be ways to inhibit neurons that are overactive, as in drug addiction.

“The cutting-edge research now available at Northern is an extremely effective recruiting tool for anyone interested in learning more about the brain and doing neuroscience research,” Rice said. “All of the faculty here were extremely helpful. I thought it would be awesome to use this technique when I first heard about it, but didn’t think it would really happen. My first week of grad school I talked to Dr. Prus and he said, ‘Let’s make it happen.’ It’s exciting.”

Prus said the involvement of five undergraduate students in the lab demonstrates NMU’s “unmatched” commitment to undergraduate research. 

“At most universities, they don’t do research,” he said. They might be cleaning beakers and that’s about it. We have a number of areas where undergrads can do real research—not simulated and not just teaching labs. It’s real research dedicated to real discoveries that get students published or send them to conferences. It’s much easier to imagine your career in solving incurable diseases if you’re doing something like that now. We’ve had students in our lab jump to huge careers because of the hands-on experience they get at Northern. I can’t imagine another university our size having these optogenetic tools.”    

Prepared By
News Director
February 15, 2016