RUI:Development and Maturation of Olfactory Centers in the Lobster:Influences of Serotonin and Life-long Neurogenesis

RUI：龙虾嗅觉中心的发育和成熟：血清素和终生神经发生的影响

• 批准号: 0344448
• 负责人: Barbara Beltz
• 金额: $ 50万
• 依托单位: Wellesley College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0344448&HistoricalAwards=false
• 关键词: RUI; Development; Maturation; Olfactory; Centers

In the past few years, it has been unequivocally demonstrated that new neurons are born and integrated into circuits in the brains of many vertebrate and invertebrate organisms, including humans. This project explores the process of life-long neurogenesis at three levels: (1) defining factors that influence the rate of neurogenesis and serotonin levels (Aim I); (2) analyzing specific effects of serotonin on the lineage of cells producing new neurons (Aim II); (3) examining the differentiation of the newborn neurons (Aim III). The lobster Homarus americanus is the focus of study because neuronal proliferation persists throughout life in the brains of these animals and is regulated by serotonin, nitric oxide and the day/night cycle. Because the factors that influence neurogenesis appear to be evolutionarily conserved, these studies may illuminate mechanisms that are relevant to the variety of species that undergo life-long neurogenesis.Aim I: Regulation of neurogenesis: developmental, behavioral and circadian controls. Dr. Beltz will examine the regulation of neuronal proliferation and serotonin by light and physical activity in larval lobsters. Her hypothesis is that the developmental change from positively phototactic, day-active larvae to negatively phototactic, night-active juvenile and adult animals, will be reflected in a change in the timing of maximal neurogenesis and in peak serotonin levels in the brain. She expects the rate of neurogenesis to be highest early in the day for larvae, in contrast to the peak at dusk for juvenile lobsters. She will ask whether increases in brain serotonin levels are a prerequisite for increases in neuronal proliferation, or whether these two elements are sometimes uncoupled, which would suggest the involvement of a non-serotonergic signaling pathway in the control of neurogenesis. Aim II: Mechanisms of proliferation of projection neurons. The proposed experiments will determine whether serotonin has a general influence on the speed of the cell cycle, or whether serotonin exerts a specific effect on this lineage by regulating the size of the large precursor cell (i.e., neuroblast) pool or the numbers of intermediate precursor cells (i.e., ganglion mother cells). She also will determine whether the divisions of the large precursor cells are symmetric or asymmetric, which has implications for the mitotic potential and fate of daughter cells.Aim III: Differentiation of newborn projection neurons. These studies will ask questions such as: Are newborn neurons integrated into the brain circuitry? Do new neurons innervate the OLs or ALs? Do altered levels of nitric oxide influence the timing or pattern of projections of newborn cluster 10 neurons? These experiments will define the single-cell circuitry and designation of functional identity of neurons that proliferate throughout the organism's life. Broader Impacts. Wellesley College is a liberal arts college for women. Therefore, an important mission of this research, beyond its intrinsic merit, is the training of our undergraduates, a high percentage of whom will continue their education in graduate or professional schools. Additional goals are to develop curricular materials for use in undergraduate courses, to acquire state-of-the-art instrumentation for teaching and research, and to give public lectures to educate non-scientists about specific topics in neuroscience, the contributions of basic research and the use of model systems.

在过去的几年里，已经明确地证明，包括人类在内的许多脊椎动物和无脊椎动物的大脑中都诞生了新的神经元，并将其整合到大脑中的电路中。该项目在三个层面上探索终生神经发生的过程：(1)确定影响神经发生速率和5-羟色胺水平的因素(目标I)；(2)分析5-羟色胺对产生新神经元的细胞谱系的特定影响(目标II)；(3)检查新生神经元的分化(目标III)。龙虾Homarus americanus是研究的重点，因为神经元增殖在这些动物的大脑中持续存在，并受到5-羟色胺、一氧化氮和昼夜周期的调节。由于影响神经发生的因素似乎在进化上是保守的，这些研究可能阐明与经历终身神经发生的物种相关的机制。目的I：神经发生的调控：发育、行为和昼夜节律控制。贝尔茨博士将研究光和体力活动对龙虾幼体神经元增殖和5-羟色胺的调节。她的假设是，从正趋光性、白天活动的幼虫到负趋光性、夜间活动的幼体和成年动物的发育变化，将反映在大脑中最大神经发生的时间和峰值5-羟色胺水平的变化上。她预计，幼体的神经发生率在一天的早期最高，而幼龙虾的神经发生率在黄昏达到最高。她会问，大脑5-羟色胺水平的增加是神经元增殖增加的先决条件，还是这两个因素有时是分离的，这可能表明非5-羟色胺能信号通路参与了神经发生的控制。目的II：投射神经元的增殖机制。拟议的实验将确定5-羟色胺是否对细胞周期的速度有普遍影响，或者5-羟色胺是否通过调节大的前体细胞(即神经母细胞)池的大小或中间前体细胞(即神经节母细胞)的数量而对这种谱系产生特定的影响。她还将确定大型前体细胞的分裂是对称的还是不对称的，这对子细胞的有丝分裂潜力和命运有影响。目的III：新生投射神经元的分化。这些研究将提出这样的问题：新生神经元是否整合到大脑回路中？是否有新的神经元支配OL或ALS？一氧化氮水平的改变是否会影响新生第10簇神经元的投射时间或模式？这些实验将定义在生物体整个生命过程中增殖的神经元的单细胞电路和功能特性的指定。更广泛的影响。卫尔斯理学院是一所面向女性的文理学院。因此，这项研究的一个重要使命，除了它的内在价值，是培养我们的本科生，他们中的很大一部分人将在研究生院或专业学校继续他们的教育。其他目标是开发用于本科课程的课程材料，获取用于教学和研究的最先进的仪器，并举办公开讲座，教育非科学家关于神经科学、基础研究的贡献和模型系统的使用的特定主题。