Grant: Project Grant

Over 1 million Canadians suffer from dementia. This disease costs our economy over $10 billion annually and robs patients of their precious memories. With no effective treatment available, these costs will only increase as our population ages. The best strategy to halt this epidemic is to first understand how the healthy brain supports memory. Traditionally, one of two methods is used: (1) high-precision neuroscience techniques in rodents, inferring that humans share the same basic mechanisms; or (2) non-invasive neuroimaging in humans, inferring neural mechanisms from indirect measurements. Both approaches, though, merely assume equivalence; combining the strengths of rodent and human neuroscience methods in a single, integrated effort is needed to uncover how memories are stored-or lost-in humans. We have assembled a team of experts in both methods to conduct parallel studies in humans and mice. We will leverage recent technical advances to 'decode' the structure of navigation memories, essentially reading a map of real-world space directly from both the rodent and human brain. We will also determine if both species build these mental maps through the same neurobiological mechanisms by applying the same physiologically-relevant manipulation to each. Specifically, in mice, we recently uncovered that memories formed close in time are more likely to be represented by the same neurons because their persistent excitability links experiences in memory. We will manipulate the time separating related learning sessions where humans or mice become familiar with digital/real environments, allowing us to determine whether memory for these environments are integrated within the human and mouse brain via similar persistent neural excitability mechanisms. By directly combining findings across species, our approach builds the foundation for further translational investigations into the basis of age and disease-related memory impairments.