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

在过去的几年里，已经明确证明，新的神经元诞生并整合到许多脊椎动物和无脊椎动物生物（包括人类）的大脑回路中。 本项目从三个层面探索终身神经发生的过程：（1）确定影响神经发生率和血清素水平的因素（目标I）;（2）分析血清素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，并受到血清素，一氧化氮和昼夜周期的调节。因为影响神经发生的因素似乎是进化保守的，这些研究可能会照亮机制，是相关的各种物种经历终身neurogenesis.Aim I：调节神经发生：发育，行为和昼夜节律控制。Beltz博士将研究龙虾幼虫中光和体力活动对神经元增殖和血清素的调节。她的假设是，从积极的趋光性，白天活跃的幼虫到消极的趋光性，夜间活跃的少年和成年动物的发育变化，将反映在最大神经发生的时间和大脑中的峰值血清素水平的变化。 她预计幼体的神经发生率在一天的早些时候最高，而幼年龙虾的神经发生率在黄昏时最高。她会问，大脑5-羟色胺水平的增加是否是神经元增殖增加的先决条件，或者这两种元素有时是否是不耦合的，这表明非多巴胺能信号通路参与了神经发生的控制。 目的二：研究投射神经元的增殖机制。所提出的实验将确定血清素是否对细胞周期的速度具有一般性影响，或者血清素是否通过调节大前体细胞的大小（即，成神经细胞）库或中间前体细胞的数量（即，神经节母细胞）。她还将确定大的前体细胞的分裂是对称的还是不对称的，这对有丝分裂的潜力和子细胞的命运有影响。这些研究将提出一些问题，例如：新生神经元是否整合到大脑回路中？新的神经元是否支配OL或AL？一氧化氮水平的改变是否会影响新生10簇神经元投射的时间或模式？ 这些实验将确定单细胞电路和指定的功能身份的神经元，增殖整个有机体的生活。更广泛的影响。韦尔斯利学院是一所女子文理学院。 因此，这项研究的一个重要使命，除了其内在的优点，是我们的本科生，其中很大一部分人将继续在研究生院或专业学校的教育培训。 其他目标是开发用于本科课程的课程材料，获得最先进的教学和研究仪器，并提供公开讲座，教育非科学家关于神经科学的特定主题，基础研究的贡献和模型系统的使用。

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.