Finding Missed Connections Among the 100 Billion

Our brains are incredibly complex machines, especially in senses like vision. But what happens when part of the machine breaks down?

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According to our best estimates, there are close to 100 billion neurons in the human brain and the specific connections they make are what let us sense and respond to the world around us.

Neuroscientist Julie Lefebvre, associate professor of molecular genetics at the University of Toronto and researcher at SickKids Hospital, maps these complex connections. She studies neural circuitry, which is a way of describing how nerve cells connect in the form of a wiring diagram.

“I want to understand how the brain works; to understand how all the different types of nerve cells that make up the nervous system, how they develop and how they make specific connections with one another,” says Lefebvre.

“It’s those connections that then give rise to function: the ability to see, or the ability to move.”

During development, nerve cells form specific patterns of connections that are essential to healthy function. When these patterns are disrupted, the defects can lead to neural disorders.

“What we want to know is how the wiring diagram of the neural circuit is organized, and what it regulates,” adds Lefebvre. “What’s its function? What particular task in the brain is it computing?”

Lefebvre studies the molecular pathways that pave the way for normal development. In particular, she’s interested in the neural circuits involved in vision to understand how the nervous system can be disrupted in blindness.

“In the retina, this is the piece of nervous tissue in your eye, it’s not just a screen. It does a lot more,” explains Lefebvre. “In order to deal with the complexity of nervous information, it has decided to organize itself into different neural circuits that have different jobs.”

Human vision actually breaks down what we see into many different aspects, like colour and motion. For patients with blindness, it’s often the neural circuits in the retina that are unable to fire or respond to visual input.

“We’re interested in understanding how we can improve or restore some of those bits that make up the neural circuits so that they can then regain some of that visual function,” says Lefebvre.

The brain is an incredibly complex structure with billions of cells and trillions of connections. Understanding how this network is organized provides a roadmap to restore healthy function when missed connections happen.

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Dr. Julie Lefebvre is a Scientist in the Neurosciences and Mental Health Program at the Hospital for Sick Children. She is also an Assistant Professor of Molecular Genetics at University of Toronto. She is Canada Research Chair in Neural Circuit Development. In 2015, she was awarded a Sloan Fellowship in Neuroscience by the Alfred P. Sloan Foundation. She earned her PhD at the University of Pennsylvania, and completed her postdoctoral training at Harvard University.

The research focus of her lab is to study how nerve cells develop and wire up into neural circuits, and to identify molecules that guide the formation of these connectivity patterns in the visual system, cortex and cerebellum. In particular, they are investigating the development of inhibitory nerves that are critical for the balance between excitation and inhibition, and that are especially vulnerable to early life insults and disease.  Her research incorporates cutting-edge microscopy, studies of animal models, and profiling the expression of molecules during brain development.  This research is motivated by the overarching goal to better understand how neural circuits develop in the healthy brain, and identify genetic and developmental alterations in circuits that underlie brain disorders. Her research is funded by the Canadian Institutes of Health Research, NSERC and Scottish Rite Charitable Foundation.

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