Grant: Operating Grant

Short-term (or "working") memory, is the memory function that we rely on in order to accomplish day-to-day tasks, like remembering a telephone number, or where we left our car keys. These memories are formed and stored via circuits of brain cells that co-ordinate many different spatial and temporal inputs. When we try and remember where our keys are, spatial cues (e.g."on the table") and temporal cues (e.g."last night") are blended into a unique neural network and stored in a brain region called the hippocampus. Interestingly, the hippocampus is also involved in the formation of navigational memories, so the route to the local Tim Hortons for example, is also contained in the hippocampus, but in a totally separate network of neurons. These networks are naturally transient and can be easily remodeled or broken when the memory needs to be changed or when it is no longer of use. For reasons that remain elusive, these hippocampal circuits are particularly vulnerable to malfunction in Alzheimer's disease (AD) patients. Indeed, one of the stereotypical clinical pathologies of AD is degeneration in short-term memory and learning, due to the death of these hippocampal neurons over a prolonged period of time. The major challenge we face, as medical experts, is the fact that when we diagnose AD, it is likely too late to initiate effective treatment. Our lab is interested in addressing this challenge. Using a well-defined experimental protocol based on the firing pattern of neurons recorded from a mouse who is forming a short term memory, we aim to record the electrical activity from multiple neurons in a network to determine how the memory is set up, used, and ultimately discarded. We will then attempt to disrupt memory formation in a way similar to that believed to occur in AD to see how the network is affected. We will even go as far as to you're going to kill a neuron in the network to see if memories can be re-routed or changed.