The van der Kooy lab uses pulses of light to mimic drug reward in the brain
U of T Researchers Demonstrate Drug-Free Activation of Opiate Reward
New research from the University of Toronto demonstrates that patterned brain stimulation can reproduce the rewarding effects of opiates without the use of drugs.
The study, published in iScience (Cell Press), was led by MoGen alum Dr. Lyla El-Fayomi and supervisor Dr. Derek van der Kooy in the Department of Molecular Genetics. Their team showed that light-based stimulation, timed to replicate the brain’s natural activity during morphine exposure, can activate reward responses in mice.
“It’s long been established that brain cells use action potentials – electrical impulses – to transmit information,” said El-Fayomi. “We demonstrated that the specific arrangement of those action potentials over time, which we refer to as neural firing patterns, are critical to this process; especially in the context of opiate use.”
The researchers used optogenetics, a genetic engineering technique that allows scientists to control neurons using pulses of light. It works by making neurons light-sensitive and then delivering light through a tiny optical fiber. The team focused on GABA neurons in the ventral tegmental area (VTA), a brain region central to reward processing. These inhibitory neurons reduce activity in other cells, and the VTA is a hub known for its role in motivation and addiction.
When the researchers replayed the exact firing patterns recorded during morphine exposure, they found that mice actively sought the stimulation, as if they had received the drug. When the sequences were scrambled, however, the animals avoided it altogether.
“We showed that a single cell type in a single region can drive three different behaviours, depending on the pattern of firing you recreate across the population,” El-Fayomi said. “This indicated that there are special arrangements of electrical impulses key to the feel-good effects of the drug.”
The experiments also revealed that VTA GABA neurons could drive reward through projections to another brain region, the tegmental pedunculopontine nucleus (TPP). This pathway worked independently of dopamine; the chemical messenger most often linked to reward. This finding suggests that more than one circuit can encode pleasurable experiences.
The findings also point to future therapeutic applications. “At the clinical level, efforts are already underway to identify pathological neural activity and correct it in disease contexts such as Parkinson’s, for example, with deep brain stimulation,” El-Fayomi explained. “This research emphasizes that better results might be achieved when we do so while prioritizing biomimicry – reconstituting the biological activity observed in relevant, healthy states to correct aberrant ones.”
This study positions addiction research within the broader global effort to map how the brain encodes behaviour. As El-Fayomi explains, “There’s a global effort to decode the brain, at the moment. Doing so will unlock a world of therapeutic possibilities.”
This work was supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, and the Canada First Research Excellence Fund’s Medicine by Design program at the University of Toronto.