Researchers at the University of Ottawa Brain and Mind Research Institute have pinpointed a set of rules that govern how brain circuits develop during early life, offering clues into neurodevelopmental disorders such as autism and schizophrenia.
Published in Neuron, one of the most influential journals in the field of neuroscience, their study shows how neuroplasticity guides brain development at the microscopic level, which ultimately sets the stage for how the mature brain operates.
Kevin Lee, a recent Faculty of Medicine PhD graduate and lead author of the project, stumbled upon this discovery during his thesis research when he noticed striking differences in calcium signals at synapses, which are specialized connections in the brain, between young, developing neurons and mature neurons.
“Until recently, neuroscientists thought that the brain wired itself up during circuit development more or less randomly at the microscopic scale,” says Jean-Claude Béïque, associate professor at the Faculty of Medicine’s Department of Cellular and Molecular Medicine and the principal investigator supervising this research. “Our results show that, during brain development, closely neighbouring synapses use calcium to communicate with each other and this ultimately influences how brain circuits wire up. Therefore, this microscopic assembly is not random, and we have identified some key rules that govern it.”
Individual neurons in the brain can harbour upwards of tens of thousands of synaptic connections. The uOttawa Faculty of Medicine’s research team used cutting-edge techniques to activate and observe individual synapses of individual neurons, one at a time.
“Rather than looking at the whole brain, we studied how circuits developed at the scale of individual neurons and individual synaptic connections. We have identified a means used by neurons to functionally organize their numerous synaptic connections,” says Lee. Researchers have long suspected that disruptions in how neurons organize their synaptic connections during brain development are intimately tied to neurodevelopmental disorders. “With this new knowledge,” Lee says, “we are now beginning to explore what this could mean for autism.”
According to Béïque, the original intent was not to research any particular disease, but rather to explore basic principles of neurobiology. In fact, he argues that, had they done research on autism per se, they likely would not have made this discovery. “It’s like trying to fix a car that won’t start when you turn the key, but barely know about the engine under the hood. To understand how it works, you need to take the car apart, explore how it’s built and tinker with it — a lot! Only then do you have a shot at fixing it. Short of doing that, you may spend a lifetime thinking the key is the problem.”
“Ultimately, it was curiosity-driven research that led to something we think is important,” says Béïque. “We stumbled onto this purely by accident. Never could we have predicted this — we even initially thought it was a bit weird. However, we took the freedom to follow the results, unsure of where they would take us or whether it was even important. Time and time again it’s been shown that academic freedom is fundamental for scientific progress. That’s the beauty of it. Curiosity-driven research in academia needs to be nurtured.”
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Original research article:
Lee KF, Soares C, Thivierge JP, Béïque JC. Correlated Synaptic Inputs Drive Dendritic Calcium Amplification and Cooperative Plasticity during Clustered Synapse Development. Neuron. 2016 Feb 17;89(4):784-99. doi: 10.1016/j.neuron.2016.01.012.