Structure and plasticity of adult neurogenesis

成人神经发生的结构和可塑性

• 批准号: 298525-2011
• 负责人: Tropepe, Vincent
• 金额: $ 2.19万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=526070
• 关键词: Structure; plasticity; adult; neurogenesis

Adult neurogenesis - the production of new neurons in the adult brain - occurs in many different types of animals and there is a growing awareness that different forms of learning and memory depend upon this process. Thus, structural changes that are due to neuron addition or replacement in the adult brain are evolutionarily conserved and functionally relevant. Among the most interesting and complex problems linked to the process of adult neurogenesis is the finding that the sensory environment seems to provide a strong stimulus for modulating the rate of new neuron production. However, we do not know the mechanism by which specific sensory cues (e.g., smell, taste or sight) influence the rate of neurogenesis in the brain. Furthermore, we do not know if specific sensory cues elicit changes in adult neurogenesis that are widespread or localized to particular brain regions for which the sensory stimulation is initially processed. Our work is driven by 3 main hypotheses: (1) the demand for new neurons in the adult brain depends upon local, region-specific requirements for this form of structural plasticity, which is reflected in the cellular organization and molecular regulation of stem and progenitor cell activity in different sites in the brain; (2) the rate of neurogenesis can be separately modulated in distinct sites in the brain to control neuron production by sensory-specific stimulation; and (3) while common molecular mechanisms regulate stem and progenitor cell identity and proliferation in all brain regions that display adult neurogenesis, relatively distinct genetic networks govern their region-specific adaptive plasticity. The goal of our research program in the next 5 years is to utilize advanced microscopy and genetics, novel sensory paradigms, and high throughput transcriptomics in order to gain important insight into the molecular and cellular organization and regional diversity of adult neurogenesis and the ability of this process to undergo adaptive plasticity at the molecular and cellular level. My long-term goal is to advance our research toward understanding how sensory modulation of genetic networks affects adult neurogenesis and how this, in turn, influences learning and memory.

成年神经发生-在成年大脑中产生新的神经元-发生在许多不同类型的动物中，人们越来越意识到不同形式的学习和记忆取决于这一过程。因此，由于成年大脑中神经元的添加或替换而引起的结构变化在进化上是保守的，并且在功能上是相关的。与成人神经发生过程相关的最有趣和最复杂的问题之一是发现感觉环境似乎提供了调节新神经元产生速率的强烈刺激。然而，我们不知道特定的感官线索（例如，嗅觉、味觉或视觉）影响大脑中神经发生的速率。此外，我们不知道特定的感觉线索是否会引起成人神经发生的变化，这些变化是广泛的还是局限于最初处理感觉刺激的特定大脑区域。我们的工作基于3个主要假设：（1）成人大脑中对新神经元的需求取决于对这种形式的结构可塑性的局部、区域特异性要求，这反映在大脑不同部位的干细胞和祖细胞活性的细胞组织和分子调控中;（2）神经发生的速率可以在脑中的不同部位分别调节，以通过感觉特异性刺激来控制神经元的产生;和（3）虽然常见的分子机制调节所有显示成人神经发生的脑区域中的干细胞和祖细胞的身份和增殖，但相对不同的遗传网络控制它们的区域特异性适应性可塑性。我们的研究计划在未来5年的目标是利用先进的显微镜和遗传学，新的感觉范例，高通量转录组学，以获得重要的洞察成人神经发生的分子和细胞组织和区域多样性，以及这个过程的能力在分子和细胞水平上进行适应性可塑性。我的长期目标是推进我们的研究，了解遗传网络的感觉调节如何影响成人神经发生，以及这反过来又如何影响学习和记忆。