Grant: Project Grant

A remarkable feature of our brains is their ability to support learning. It is widely accepted that the connections between neurons, or synapses, are capable of plastic changes. Synaptic plasticity adapts neural circuits to encode learning. However, there are thousands of synapses in a circuit, and we do not know why specific synapses are chosen to undergo plasticity. As a consequence, we cannot predict how exactly neural circuits are changed by learning, either in health or in disease. We address this fundamental problem by investigating a brain region called the cerebellum in mice, which supports the learning of precise and well-calibrated movements. Thus, forms of cerebellum-dependent motor learning can be reliably induced and measured with a high degree of accuracy. Moreover, it is particularly important to understand the cerebellum because it is strongly implicated in mental health disorders such as autism, but remains understudied. In this project, we propose to identify how plasticity serves to support learning, at multiple levels of analysis - from molecules and synapses, to neural circuits and behavior. Our preliminary results identify that plasticity is shaped by experience so that it is optimized for different behaviors. Our overall goal is to identify how and why this occurs. This knowledge is critical to understand how the brain itself can be modified, in response to injury, disease or aging. Both in Canada and worldwide, mental health disorders remain a major contributor to human suffering and economic burden - partly because effective therapies are lacking. In turn, the lack of therapies stems from a lack of knowledge about how the brain works. The proposed research into the mechanisms of learning and how these learning mechanisms can be disrupted, shaped or regulated, is thus essential for the development of effective therapeutic strategies for the broad spectrum of disorders where learning is perturbed.