Researchers at the University of Rochester have demonstrated a noninvasive technique called bioluminescent optogenetics, or BL-OG, that uses light to stimulate brain neurons. Controlling brain activation has the potential to revolutionize invasive neurosurgical treatments like deep brain stimulation for neurological disorders like Parkinson's disease.
According to Manuel Gomez-Ramirez, an Assistant Professor of Brain and Cognitive Sciences at the University's Del Monte Institute for Neuroscience and the Study's Senior Author, the benefit of this new method is that it can produce brain activation without the need for an implanted device in the brain to deliver physical light.
BL-OG is an ideal method for noninvasively teasing apart neural circuits in the brain. 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.”
Emily Murphy, Study First Author, Haptics Lab, University of Rochester
How to Turn on a Light Without a Switch
Researchers require some instruments to switch on light in the brain. The first is optogenetics, a well-established scientific method that modifies brain cell activity with light. The next technique is bioluminescence, the same chemical reaction that gives a firefly its glow, which supplies the light optogenetics required to work.
The material required for BL-OG is created by combining these tools. However, someone still has to “turn on” the light for BL-OG to function. When mixed with bioluminescence, the organic molecule luciferin provides light that triggers optogenetics and regulates cellular response in the brain without an incision. Gomez-Ramirez's earlier research has demonstrated that luciferin is a molecule that is safe for the body.
This combination was evaluated by the Haptics Lab researchers. In mice, they injected BL-OG into a predefined area of the brain. To trigger the specific brain cells, they injected luciferin into the animal's tail vein. They discovered that whereas BL-OG effects happen quickly in the brain, the animal's luciferin dosage might regulate these effects.
“Fine-Tuning” Bioluminescent Optogenetics
The advantage of this technique is we can create brain activation without a cable. There is less risk of infection and other things going awry because it is a non-invasive method. 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.”
Manuel Gomez-Ramirez, Assistant Professor and Study Senior Author, University of Rochester
Another possible aspect of this technique that may provide light on how the brain functions is the bioluminescent activity, which allowed researchers to follow the neuromodulation effects of BL-OG.
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Journal reference:
Murphy, E. F., et al. (2024) Strength of Activation and Temporal Dynamics of BioLuminescent-Optogenetics in Response to Systemic Injections of the Luciferin. NeuroImage. doi.org/10.1016/j.neuroimage.2024.120882.