Structure and plasticity of adult neurogenesis

许多不同种类的动物都有成年神经发生，即在成年大脑中产生新的神经元。人们越来越认识到，不同形式的学习和记忆都依赖于这一过程。因此，在成人大脑中，由于神经元的增加或替换而引起的结构变化是进化保守的，并且与功能相关。在与成人神经发生过程有关的最有趣和最复杂的问题中，发现感觉环境似乎为调节新神经元产生的速度提供了强烈的刺激。然而，我们不知道特定的感觉线索（如嗅觉、味觉或视觉）影响大脑中神经发生速率的机制。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，这种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)成人大脑对新神经元的需求取决于对这种结构可塑性形式的局部、区域特异性需求，这反映在大脑不同部位的细胞组织和干细胞和祖细胞活性的分子调节中；(2)神经发生的速率可以在大脑的不同部位单独调节，通过感觉特异性刺激来控制神经元的产生；(3)虽然在所有显示成人神经发生的大脑区域中，共同的分子机制调节着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着它们的区域特异性适应可塑性。未来5年，我们的研究目标是利用先进的显微镜和遗传学、新颖的感觉范式和高通量转录组学，以获得对成人神经发生的分子和细胞组织和区域多样性的重要见解，以及这一过程在分子和细胞水平上经历适应性可塑性的能力。我的长期目标是推进我们的研究，以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。

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.