The role of immature neurons in hypothalamic plasticity from small to large brain mammals

点击翻译按钮获取中文摘要

My central research program examines the cellular and molecular mechanisms underlying hypothalamic development, with an emphasis on neurogenesis: the birth of new neurons. To date, all our studies have focused on embryonic neurogenesis, with recent data now leading us to test herein a novel mechanism for hypothalamic plasticity in the adult. Based on our unexpected observation that the adult hypothalamus is enriched with immature neurons, we propose these cells are primed for functional integration as needed. In the classic view, adult neurogenesis occurs across well-defined stages, whereby neural stem cells in these niches become re-awakened, then proliferate and differentiate into mature neurons that then migrate to the proper location to be integrated into functional circuits. However, the integration of newly born neurons in the adult brain is restricted to regions serviceable by these stem cell niches, leaving vast regions of the brain untouched, especially in large brain mammals. Adult neural plasticity, in contrast, is the integration of new neurons into existing connections, which can occur throughout the brain parenchyma and might have evolutionary advantages. In the adult, we made the surprising discovery that the hypothalamic parenchyma is enriched with doublecortin (DCX+) immature neurons that were BrdU- (e.g., not newly born during adult neurogenesis). This unexpected finding is the backbone for this proposal and led to our hypothesis that the hypothalamic parenchyma is populated with immature neurons born during embryogenesis that remain primed for induction into neuronal circuits as needed to adapt to environmental challenges in the adult. We test this hypothesis across two aims: Aim 1. To characterize DCX+ immature neurons in the hypothalamus across species and ages Aim 2. To determine the functional fate and requirement of DCX+ immature neurons in the murine adult hypothalamus in response to a high-fat diet challenge Overall, this study will provide a mechanistic understanding into the role of these immature neurons in driving plasticity in the adult hypothalamus, as well as provide an evolutionary context as to how brain regions not served by adult neurogenic niches might maintain plasticity. Our HQP will learn a range of cutting-edge molecular, cellular, and behavioral techniques, which will position them as leaders in Canada's natural sciences sector.