PHOTIC ENTRAINMENT OF CIRCADIAN BEHAVIORS

描述(改编自申请者的摘要)：这个项目将 研究SCN内神经化学信号如何相互作用以实现同步化 昼夜循环的行为的昼夜节律。由于精神障碍 昼夜节律计时系统与多种心理活动有关 疾病，了解昼夜节律的神经生物学应该导致 为这些疾病开发新的治疗方法。至少三个 SCN的不同传入投射参与了光反应。 昼夜节律的夹带。RHT是从 对于夹带来说是必要的和充分的视网膜。投射自 中缝和种间叶对SCN也有影响。 夹带，尽管它们不提供夹带所需的输入 进程。这些传入投射中包含的神经化学信号 以及在SCN固有的神经元中以复杂的方式相互作用 控制光的夹带。这个项目的长期目标是定义 通过定义昼夜节律夹带的神经化学基础 光信息如何传递到SCN并在其中进行处理。 具体目的我将检验EAA是一种神经递质的假设 其通过RHT将光信息传送到SCN。自.以来 研究人员已经能够证明注射一种EAA激动剂 (即NMDA)进入SCN体内可以模拟SCN的相移效应 莱特，这将有可能解决关于这一重大分歧 假设。特定目标2将测试P物质的假设，这是 似乎包含在RHT中，有助于通过 调节SCN中EaAs的活性。《特定目标3》将展开调查 本征SCN对光的相移效应的影响 神经回路和SCN的传入投射。具体地说， 研究人员将检验GABA、5-羟色胺和NPY抑制 通过抑制相移效应实现光的相移效应 在SCN中的EaS和/或P物质。

DESCRIPTION (Adapted from applicant's abstract): This project will investigate how neurochemical signals interact within the SCN to synchronize circadian rhythms in behavior with the day-night cycle. Since disorders of the circadian timing system have been linked to a variety of mental illnesses, understanding the neurobiology of circadian rhythms should lead to the development of new treatments for these diseases. At least three different afferent projections of the SCN are involved in the photic entrainment of circadian rhythms. The RHT is a direct projection from the retina that is necessary and sufficient for entrainment. Projections from the raphe and the intergeniculate leaflet to the SCN also influence entrainment although they do not provide input necessary for the entrainment process. The neurochemical signals contained in these afferent projections as well as in neurons intrinsic to the SCN interact in a complex manner to control photic entrainment. The long-term goal of this project is to define the neurochemical basis of the entrainment of circadian rhythms by defining how photic information is communicated to and processed within the SCN. Specific Aim I will test the hypothesis that an EAA is a neurotransmitter which communicates photic information to the SCN through the RHT. Since the investigator has been able to demonstrate that injection of an EAA agonist (i.e., NMDA) into the SCN in vivo can mimic the phase shifting effects of light, it will be possible to resolve a significant discrepancy about this hypothesis. Specific Aim 2 will test the hypothesis that substance P, which appears to be contained in the RHT, contributes to the entrainment by modulating the activity of EAAs in the SCN. Specific Aim 3 will investigate how the phase shifting effects of light are influenced by intrinsic SCN circuits and by afferent projections of the SCN. Specifically, the investigator will test the hypothesis that GABA, serotonin and NPY inhibit the phase shifting effects of light by inhibiting the phase shifting effects of EAAs and/or substance P in the SCN.