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

描述（改编自申请人摘要）：视交叉上核 (SCN)是哺乳动物的主要“生物钟”， 动物表达的昼夜节律。 AVP在SCN中的作用是 钙离子依赖性PKC同工酶的意义， SCN功能未知。 在小鼠中，PKCalpha存在于所有 AVP阳性和许多AVP阴性神经元。 PKCalpha可能在 SCN内AVP阳性和AVP阴性神经元之间的信号传导 通过V1a类受体通过磷酸肌醇周转， PKC的激活。 不同选择的鼠标线的数量不同， SCN中的AVP、PKCalpha和PKC β 1神经元。 的差异 SCN中AVP、PKCalpha和PKC β 1神经元的数量与 轮跑活动的几个昼夜节律参数， 在恒定黑暗中对15分钟光脉冲的相位延迟响应。 因此，这些线路代表了一个独特的机会， AVP和Ca2+依赖的PKC同工酶和光的功能作用 SCN中的转导途径，通过使用种内差异， 神经解剖学和昼夜节律行为。 以下假设将 测试：（1）PKC免疫反应性仅限于一组不同的 神经元表型也在所选品系中不同。 (2)的 在AVP和PKC免疫反应性的昼夜节律中， SCN。 (3)相位延迟响应的幅度与 SCN中在光脉冲后表现出Fos诱导的细胞数量。 (4)各品系间SCN中AVP免疫反应性的差异如下： 与血浆糖皮质激素节律的变化相关。 (5)行为 细胞系之间的差异是由于SCN中PKC的不同水平。 脑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 线条之间的节奏将被测量。 也将确定 是否将Ca2+依赖性PKC抑制剂长期施用到 SCN可以改变轮运行活动的昼夜参数。 这项建议 解决了关键监管机制的功能意义， SCN影响生理和行为特征。 它将有助于 对于哺乳动物生物钟如何适应 地球的昼夜循环，因此， 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.