Mechanisms of experience-dependent hippocampal neurogenesis

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This research program investigates how the brain is shaped by life experiences. Indeed, it has been known for over half a century that the brain's anatomy, chemistry, and function are powerfully influenced by experiences such as stress, physical activity, and cognitive training. The ability of the brain to be shaped by experience is called plasticity, and it is one of the brain's defining features. Understanding how this occurs will help us understand key brain functions, such as the ability to learn and remember. Our long-term goal is to develop an integrated model, from life experiences to gene, of how life experience regulates brain plasticity. We focus on the hippocampus, one of the rare regions of the adult brain that is capable of neurogenesis (the process by which brain stem cells produce new brain cells). Remarkably, hippocampal neurogenesis can be measurably changed simply by placing mice in different housing environments that are enriched with a running wheel, social interactions and/or stressors. This discovery serves as a model for the fundamental questions we are pursuing here. In our prior work, we started at the behavioral level, developing housing models that allowed us to demonstrate that individual elements within an enriched environment (such as physical activity, cognitive stimulation, stress, and social interactions) affect the hippocampus in different ways. This prior work identified potential pathways by which such experiences "talk" to the brain. Based on our findings, we now propose to expand our work at the cellular and molecular levels. We will use state of the art technologies that describe how each of the thousands of cells in the hippocampus is behaving when an animal is exposed to exercise, and use advanced animal models to identify the cellular processes that are mediating these responses to exercise. This research program will generate fundamental biological insights into the mechanisms of brain plasticity, which is an essential feature of how our brains function. Importantly, this project will also provide highly qualified personnel with valuable, specialized and versatile expertise for future academic, industrial and regulatory positions.