Trophic Factors and the Development of Neural Circuitry

神经递质似乎在神经系统的发育过程中发挥关键作用，除了它们作为成熟大脑中的信号分子的功能。然而，这些分子的神经源性作用尚未完全阐明。这些实验将检验神经递质5-羟色胺（5-HT）是模型系统黑腹果蝇（Drosophila melanogaster）中中枢神经系统（CNS）电路正常发育的关键营养因子的假设。CNS发育过程中5-HT水平的变化应影响神经回路的发育，从而影响成熟CNS的功能。遗传和转基因工具将用于组成性改变5-HT水平，以确定正常电路和CNS功能都受到影响。类似的工具将用于在时间和空间上破坏正常神经元5-HT水平，以将5-HT的神经源性作用与其作为不同行为的调节剂的功能分开。该奖项将重点关注神经支配肠道以及触角叶和蘑菇体的纤维，因为这些纤维数量有限，因此提供了一个简单的系统来评估静脉曲张，分支和细胞数量的变化。这些回路的功能将通过评估进食和嗅觉行为来分析，这些行为已被证明受到神经元5-HT水平改变的影响。这些实验将阐明5-HT在发育中的肠道和嗅觉回路中的神经原性作用，并建立这一过程中缺陷的功能后果。这项研究计划解决了一个关键的生物学问题（CNS电路的发展），并将产生许多试剂，将提供给科学界。在该奖项下开展的活动将对科学教育和培训产生直接影响。几个本科生直接参与了NSF的研究项目从这个实验室;七个已在论文的合著者，并在科学会议上介绍了他们的工作。此外，Neckameyer博士还在她的实验室里接待了高中教师和学生，以教授她工作中使用的概念和技术。

Neurotransmitters appear to play critical roles during development of the nervous system in addition to their functions as signaling molecules in the mature brain. However, the neurogenic roles for these molecules have not been fully elucidated. These experiments will test the hypothesis that the neurotransmitter serotonin (5-HT) is a trophic factor critical for the normal development of central nervous system (CNS) circuitry in the model system Drosophila melanogaster. Changes in 5-HT levels during CNS development should affect the development of the neural circuitry, and therefore affect functioning of the mature CNS. Genetic and transgenic tools will be used to constitutively alter 5-HT levels to establish that both the normal circuitry and the function of the CNS are affected. Similar tools will be used to temporally and spatially disrupt normal neuronal 5-HT levels to separate the neurogenic role of 5-HT from its function as a modulator of different behaviors. This award will focus on the serotonergic fibers innervating the gut as well as the antennal lobes and mushroom bodies, since these fibers are limited in number and thus provide a simple system in which to assess changes in varicosities, arborizations, and cell number. The function of these circuits will be analyzed by assessing feeding and olfactory behaviors, which have been shown to be affected by altered neuronal 5-HT levels. These experiments will elucidate the neurogenic role of 5-HT in the developing gut and olfactory circuitry and establish the functional consequences of defects in this process. This research program addresses a critical biological question (development of CNS circuitry), and will generate numerous reagents that will be made available to the scientific community. Activities to be carried out under this award will have a direct impact on scientific education and training. Several undergraduates have directly participated in NSF research projects from this laboratory; seven have been coauthors on papers, and have presented their work at scientific meetings. In addition, Dr. Neckameyer has also hosted high school teachers and students in her laboratory in order to teach the concepts and techniques used in her work.