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.
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