uOttawa researchers shed light on how cannabis alters a depression-related brain circuit

Posted on Tuesday, May 17, 2016

Using a powerful technique known as optogenetics that allows for the control of neuronal activity with light, researchers at the University of Ottawa Brain and Mind Research Institute (uOBRMI) have provided a functional description of an important pathway in the brain that is implicated in depression and anxiety. Moreover, they have pinpointed a mechanism by which the active ingredient in cannabis alters the function of this brain circuit.

Recently published in the Proceedings of the National Academy of Sciences (PNAS), the study led by Sean Geddes, a research associate in Professor Jean-Claude Béïque’s lab at the Faculty of Medicine, identified functional rules that govern how the prefrontal cortex controls the activity in the brain of neurons that secrete serotonin, a neurotransmitter involved in mood regulation that is targeted by drugs such as Prozac.

“The prefrontal cortex — a part of the brain involved in higher-order cognitive function — sends signals to serotonin neurons located in a region called the raphe,” explains Geddes. “In our latest research, we showed how the signals from this cortical region are processed in the raphe. Essentially, the prefrontal cortex activates serotonin neurons in the raphe, but that activation is usually kept in check by nearby inhibitory neurons that act as a break on serotonin neurons.”

Interestingly, Geddes found that cannabinoids cause an overall drop in prefrontal cortex drive to inhibitory cells in the raphe, leaving largely unaltered the direct excitation of serotonin neurons. This mechanism will have profound effects on serotonin output throughout the brain and may ultimately control the fine line between healthy and unhealthy levels of serotonin in the brain. This process can potentially speak to the general mood-altering features of marijuana use.

“This is something that wasn’t well understood before because these two regions in the brain — the prefrontal cortex and raphe —are so far from each other that, historically, it has been difficult to study these specific pathways in isolation amongst the incredibly large number of pathways and networks in the brain,” says Béïque, an associate professor in the Department of Cellular and Molecular Medicine.

However, scientists in the last 10 years or so have been able to study the roles of specific brain circuits with extraordinary precision using optogenetics — a high-tech and exploding methodology that provides the ability to control specific neurons in the brain with light.

“In this case, we used optogenetics to specifically activate the prefrontal cortex’s inputs to the raphe by using light,” explains Béïque. This cutting-edge technology, now used by several labs at the University of Ottawa, is revolutionizing our ability to study the brain.

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