Environmental Regulation of Neurogenesis

描述（由申请人提供）：目前临床抑郁症的一种理论提出，海马中神经发生的消长与该疾病的发作和恢复有因果关系。因此，确定调节神经发生的因素可能对理解这种疾病和开发新的治疗方法至关重要。 我们对疾病机制的了解可以通过研究模型系统来扩展，在模型系统中，神经发生可以被严格控制，并且可以在生理上可行的制剂中在单个识别的神经元的水平上进行定量分析。甲壳类动物的大脑为我们提供了这样一个模型系统。5-羟色胺水平、活动模式和生活条件影响该系统中神经元增殖的速率，就像哺乳动物的大脑一样。此外，昼夜节律控制的神经细胞周期在甲壳类动物的大脑是第一个例子，光夹带的神经发生在任何系统，提高了可能性，光可能会提供一个主导的协调信号的许多因素，影响神经元的增殖。 这项提议的主要目标是了解光在控制神经发生中的作用。我们建议，在十足类甲壳动物大脑的调节途径之一，通过两个由内源性振荡器驱动的巨能神经元。我们的假设是，这些神经元通过在神经元增殖发生的部位释放5-羟色胺来调节神经发生。将使用细胞增殖标记方法、高压液相色谱法、免疫细胞化学和电生理学在完整动物和分离的脑制备物中的组合来测试该假设，在所述分离的脑制备物中，可以在生理学上操纵肾上腺素能巨神经元以测试它们参与控制通路。光周期，血清素水平和神经发生率之间的关系也将被检查，并定义在调节神经发生中重要的光感受系统。

DESCRIPTION (provided by applicant): One current theory of clinical depression proposes that the waxing and waning of neurogenesis in the hippocampus are causally related to the onset of, and recovery from, episodes of this disease. Defining the factors that regulate neurogenesis may therefore be of critical importance in understanding this disease and developing novel therapies. Our knowledge of disease mechanisms can be extended by studying model systems where neurogenesis can be tightly controlled and where quantitative analyses can be conducted at the level of individual identified neurons in physiologically viable preparations. The crustacean brain provides us with such a model system. Serotonin levels, activity patterns, and living conditions influence the rate of neuronal proliferation in this system, just as in the mammalian brain. In addition, circadian control over the neuronal cell cycle in the crustacean brain is the first example of light entrainment of neurogenesis in any system, raising the possibility that light may provide a dominant coordinating signal for the many factors that influence neuronal proliferation. The primary goal of this proposal is to understand the role of light in the control of neurogenesis. We propose that one of the regulatory pathways in the decapod crustacean brain operates via two serotonergic giant neurons that are driven by the endogenous oscillator. Our hypothesis is that these neurons regulate neurogenesis by releasing serotonin at the site where neuronal proliferation occurs. This hypothesis will be tested using a combination of cell proliferation labeling methods, high pressure liquid chromatography, immunocytochemistry and electrophysiology in intact animals and in isolated brain preparations in which the serotonergic giant neurons can be manipulated physiologically to test their involvement in the control pathway. The relationship between photoperiod, serotonin levels and the rate of neurogenesis also will be examined, and the photoreceptive system(s) that are important in regulating neurogenesis will be defined.