Mechanisms of experience-dependent hippocampal neurogenesis

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My NSERC-funded research program tackles the question of how life experience shapes brain structure and function. Plasticity, or the ability to be dynamically changed by life experience, is one of the brain's defining features. The production of new neurons by neural stem cells in the hippocampus, a structure involved in learning, memory and emotion, is one such form of plasticity. By focusing on this process of hippocampal neurogenesis, our long-term goal is to develop an integrated model, from behaviour to genes, of how life experience regulates brain function.*** Mice are a simple but powerful mammalian model for studying this question, as their living environments can be tightly controlled, they can be used for genetic manipulations to test specific hypotheses, and their brain function can be measured using tests of learning, memory and emotion. Mice housed in an enriched environment (EE) have better learning and memory and more hippocampal neurogenesis, but it has long been unclear what EE elements are responsible (Physical exercise? Cognitive challenges? Social hierarchies? Stress? Sensory stimulation?). In the preceding stage of this research program, my trainees overcame this major hurdle, developing a novel EE strategy that successfully separates the impact of such factors (our first major goal). We are now testing whether each of these factors contributes to changes in learning, memory and/or emotions.*** Our second major goal is to identify genetic changes occurring at the level of the hippocampus itself in response to each EE factor. My PhD and postdoc students are collaborating using cutting-edge genetic and mass spectrometry approaches to uncover the local mediators of change in hippocampal function. Our third major goal is to then identify the circulating signals by which an enriched environment “talks” to the hippocampus to trigger these genetic changes. My first postdoc student is testing the specific hypothesis that EE-induced hormonal fluctuations are systemic mediators of neurogenesis changes.*** Our research program will generate fundamental insights into environment-brain interactions. These studies will provide an integrated, multi-level analysis that links life experiences to changes in brain gene expression and stem cell activity. HQP will receive training that is diverse, from the behavioural to the genetic levels, representing valuable, specialized and versatile expertise for positions in academia, stem cell industry, and government regulation.**