Mechanisms and outcomes of stress-induced changes to neurogenesis in zebrafish

点击翻译按钮获取中文摘要

Fish are unique among vertebrates in having a high capacity to add and incorporate new neurons across the entire adult brain. Understanding how and why fish do this remains an open question; and therefore researching neurogenesis in non-traditional species, like fish, may lead to novel treatment strategies for brain injuries, neurodegenerative diseases, and psychiatric disorders. Past studies show that neurogenesis in fish can be modified by abiotic and social factors, and this may provide a substrate by which fish adapt to environmental change. Understanding the regulation and functions of neurogenesis in such contexts will deepen this ecological and evolutionary perspective. My Discovery Program will investigate the mechanistic and functional connections between stress and adult neurogenesis in fish. We know that stress has a profound influence on the brain, and recent studies suggest that the major stress hormone, cortisol, can influence neurogenesis. Increased cortisol levels in response to stress may therefore be an important mechanism by which important behavioural and physiological responses are solidified in the central nervous system. At the same time, chronic stressors are an increasing occurrence in the natural environment, but whether or not this leads to longterm suppression of neurogenesis with maladaptive outcomes is unknown. Over the next 5years, I will use zebrafish as a model to: (i) build core knowledge on the dynamic effects of stress on neurogenesis; (ii) define the cellular pathways that regulate cortisol signalling within neurogenic regions of the brain; and (iii) explore the adaptive significance of neurogenic plasticity by integrating cell fate tracking experiments with behavioural and physiological assays. These experiments will push the boundaries of comparative neurogenesis by defining key mechanistic and functional metrics that underlie the intriguing ability of fish to make and incorporate new neurons into the adult brain. My innovative research program provides a rich and stimulating training environment for HQP, where students will engage in multidisciplinary and integrative research that uses genetic and pharmacological tools to decipher physiological pathways from molecules to whole animals.