(A) Schematic illustration of the LMO7 molecule. (B) Representative histological images showing fluorescence expression in the left SI of a mouse. (C) Illustration of the timeline of events within a single day of imaging. (D) Schematic of the experimental setup used to image bioluminescence in the mouse. Credit: NeuroImage (2024). DOI: 10.1016/j.neuroimage.2024.120882

University of Rochester researchers have demonstrated a noninvasive method using BL-OG, or bioluminescent optogenetics, that harnesses light to activate neurons in the brain. The ability to regulate brain activation could transform invasive procedures such as deep brain stimulation that are used to treat Parkinson’s disease and other neurological conditions.

The advantage of this new technique is that it can create brain activation without the use of an implanted device in the brain to deliver physical light, according to Manuel Gomez-Ramirez, an assistant professor of brain and cognitive sciences and with the University’s Del Monte Institute for Neuroscience, and the senior author of the study, which appears in the journal NeuroImage.

“BL-OG is an ideal method for noninvasively teasing apart neural circuits in the brain,” says Emily Murphy, the first author of the study and manager of the Haptics Lab, led by Gomez-Ramirez. “There are still so many things to learn about the structure and function of distinct brain areas and neuronal cell types that will help us understand how healthy brains function.”

How to turn on a light—without a switch

To turn on light in the brain, researchers need a few tools. The first one is optogenetics, an established research technique that uses light to activate or inactivate cells in the brain. The next tool is bioluminescence, the same chemical reaction that gives a firefly its glow, which provides the light optogenetics needs to work.

Combining these tools creates the material needed for BL-OG. But in order to work, BL-OG still needs something to “turn on” the light. The organic substance luciferin, when combined with bioluminescence, creates light that activates the optogenetics and modulates cellular response in the brain without an incision. Previous work by Gomez-Ramirez has shown that the chemical luciferin is harmless to the body.

The researchers in the Haptics Lab tested this combination. They put BL-OG into a pre-determined brain region in mice. They then injected luciferin through a vein in the animal’s tail to activate the targeted cells in the brain. They found that BL-OG effects occur rapidly in the brain, but that these effects could be controlled by scaling the dosage of the luciferin in the animal.

‘Fine-tuning’ bioluminescent optogenetics

“The advantage of this technique is we can create brain activation without a cable. There is less risk for infection and other things to go awry because it is a noninvasive method,” Gomez-Ramirez says.

“If we want to standardize this technique in the lab, and potentially in the clinic, it is critical to map all the important parameters around using it. These latest findings allow us to now work on fine-tuning the desired effects of BL-OG based on need and requirements.”

Researchers were also able to track the neuromodulation effects of BL-OG through the bioluminescent activity, another potential feature of this method that could provide insight into how the brain works.