MODEL TO STUDY THE ROLE OF AVP, PKC, AND FOS IN THE SCN

描述(摘自申请者的摘要)：视交叉上核 (SCN)是哺乳动物的主要“生物钟”，控制着大多数 由动物表达的昼夜节律。高级副总裁在SCN中的作用是 钙依赖的PKC同工酶在脑出血中的意义 SCN功能未知。在小鼠中，PKCalpha存在于所有 AVP阳性神经元和许多AVP阴性神经元。PKCalpha可能在 孤束核内AVP阳性神经元和AVP阴性神经元之间的信号转导 通过V1a类受体通过磷酸肌醇周转和 激活PKC。不同选择的鼠标行在数量上有所不同 SCN内AVP、PKCalpha和PKCbeta1神经元。两个国家之间的差异 脊髓核内AVP、PKCalpha和PKCbeta1神经元的数量与 车轮跑活动的几个昼夜节律参数和 在恒定黑暗中对15分钟光脉冲的相位延迟响应。 因此，这些线条代表着调查 AVP和钙依赖的PKC同工酶与LIGH的功能作用 在SCN中利用种内差异的转导途径 神经解剖和昼夜节律行为。以下假设将是 测试：(1)PKC免疫反应性仅限于一组不同的 神经细胞表型在所选品系中也不同。(2) 不同品系AVP和PKC免疫反应的昼夜节律不同 SCN.(3)相位延迟响应的大小与 在光脉冲后表现出Fos感应的SCN中的单元数。 (4)AVP免疫反应性在不同品系间的差异如下： 与血浆糖皮质激素节律的变化相关。(5)行为举止 不同品系之间的差异是由于SCN中PKC水平的不同所致。 脑组织切片的单标记和双标记免疫细胞化学 将使用SCN。此外，血浆糖皮质激素的变化 将测量线条之间的节奏。它也将被确定 慢性给予钙离子依赖的PKC抑制剂是否 SCN可以改变轮子活动的昼夜节律参数。这项建议 阐述了内部关键监管机制的功能重要性 影响生理和行为特征的SCN。它将做出贡献 对哺乳动物生物钟如何适应的一般理解 个人对地球的昼夜循环，因此，将推进 与人类健康有关的问题。

DESCRIPTION (Adapted from applicant's abstract): The suprachiasmatic nuclei (SCN) are the major "biological clocks" in mammals and control most circadian rhythms expressed by the animal. The role of AVP in the SCN is poorly understood, and the significance of Ca2+-dependent PKC isozymes in SCN function is not known. In the mouse, PKCalpha is present in all AVP-positive and many AVP-negative neurons. PKCalpha may play a role in signaling between AVP-positive and AVP-negative neurons within the SCN through the V1a class of receptors via phosphoinositol turnover and activation of PKC. Divergently selected mouse lines differ in the number of AVP, PKCalpha, and PKCbeta1 neurons in the SCN. The differences in the number of AVP, PKCalpha, and PKCbeta1 neurons in the SCN correlate with several circadian rhythm parameters of wheel-running activity and phase-delay responses to 15-min light pulses in constant darkness. Therefore, these lines represent a unique opportunity to investigate the functional role of AVP and Ca2+-dependent PKC isozymes and light transduction pathways in the SCN by using within-species differences in neuroanatomy and circadian behavior. The following hypotheses will be tested: (1) PKC immunoreactivity is restricted to a distinct group of neuronal phenotypes that also differ among the selected lines. (2) The lines differ in the circadian rhythms in AVP and PKC immunoreactivity in the SCN. (3) The magnitude of the phase-delay response is proportional to the number of cells in the SCN that exhibit Fos induction after a light pulse. (4) Differences in AVP immunoreactivity in the SCN among the lines are correlated with variance in plasma glucocorticoid rhythms. (5) Behavioral differences among the lines are due to different levels of PKC in the SCN. Single and double labeling immunocytochemistry of brain sections containing the SCN will be used. In addition, the variance in plasma glucocorticoid rhythms among the lines will be measured. It will also be determined whether chronic administration of a Ca2+-dependent PKC inhibitor into the SCN can alter circadian parameters of wheel-running activity. This proposal addresses the functional significance of key regulatory mechanisms within the SCN influencing physiological and behavioral traits. It will contribute to the general understanding of how the circadian clock in mammals adapts individual to the earth's day-night cycle and, therefore, will advance issues related to human health.