Grant: Doctoral: Vanier Canada Graduate Scholarships

Huntington's disease (HD) is a devastating inherited disease that can be detected before symptoms arise, but which is incurable. In HD patients, neurons involved in motor functions deteriorate, causing motor and cognitive problems. Neurons transmit signals in our brains, relying heavily on calcium for their function. The function impairment of the connections between neurons, known as synaptic function, as well as their ability to control calcium levels, form a common trait of many neurodegenerative disorders such as Parkinson's, Alzheimer's, and HD. One level of calcium control is at the endoplasmic reticulum (ER), a cell organelle playing a significant part in protein production. This calcium regulation is abnormal in HD, leading to a change in protein production and a decrease in synaptic function. Interestingly, activating Sigma-1 receptors (S1Rs) - proteins located on the ER that play an important role in calcium regulation and therefore protein production - has been shown to normalize this calcium handling and restore synaptic function. The purpose of this project is to determine the relationship between S1Rs, protein production, calcium handling, and synaptic function, in order to better understand the disease mechanisms of HD and other neurodegenerative diseases, and to find new potential treatments. To conduct this project, I will utilize electrophysiological, pharmacological, imaging, and behavioral techniques. As there are currently no effective treatments for HD, the results from this study may revolutionize our approach to patients with this debilitating disease.