NEURAL BASIS OF BIOLOGICAL RHYTHMS

生物节律的神经基础

• 批准号: 2265960
• 负责人: MARY E HARRINGTON
• 金额: $ 15.18万
• 依托单位: SMITH COLLEGE
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-15 至 1996-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2265960
• 关键词: aspartate; circadian rhythms; excitatory aminoacid; gene expression; glutamates; hamsters; kainate; neurobiology; neurochemistry; neurotransmitters; oncogenes; photostimulus; suprachiasmatic nucleus; voltage /patch clamp

DESCRIPTION (Adapted from applicant's abstract): Light and some other stimuli are known to control the phase of circadian rhythms. A particular stimulus can advance, delay, or have no effect on the phase depending on when within the circadian cycle it is delivered. These responses can be characterized as phase response curves (PRC). PRCs for light pulses are different from PRCs to dark pulses or non- photic stimuli. The proposed research seeks to investigate the neural and neurochemical bases for these PRCs in a brain slice preparation which contains the suprachiasmatic nuclei, a known circadian clock in mammals. By sampling extracellular firing rates from many SCN cells over the course of several days, a circadian rhythm in firing frequency can be identified. The major goal of the proposed research is to establish which transmitter substances applied in vitro at 6 different times of day induce phase shifts in the population rhythm. One route by which light information is transmitted to the SCN is the retino-hypothalamic tract. The first experiment tests the hypothesis that EAA, believed to be transmitters in retino-hypothalamic neurons, phase shifts the SCN population rhythm like light pulses. Glutamate, acetylaspartyl-glutamate, aspartate, NMDA, quisqualate and kainate will be tested. If phase shifts are obtained, receptor blockers are used to identify postsynaptic receptor types. Based on recent results, histamine will also be tested. An indirect route from the eye to the SCN is via the intergeniculate leaflet, the geniculo-hypothalamic tract (GHT).Phase shifts obtained by stimulating this pathway mimic dark pulse or non- photic PRCs. A second experiment tests the putative transmitters of the GHT, namely, NPY, met-enk and GABA for phase shifting effects on SCN activity. Furthermore, RHT and GHT transmitters will be applied in combination to assess interactions among these transmitters (e.g., RHT transmitters may block or reduces the effects of GHT transmitters). Light pulses are known to induce c-fos and related immediate early genes in the SCN and intergeniculate leaflet, but not in other retino-recipient targets. A second aim of the proposed research is to assess which transmitter substances have the capacity to induce c-fos expression in SCN neurons in vitro. The hypothesis is that only transmitters which mimic a light pulse PRC will induce c-fos. A third aim of the proposed experiments is to assess direct effects of the transmitters used in aims 1 and 2 on the firing rate of SCN neurons. Neurochemical are given at 5 doses and at different times of day since a neuron's response may change throughout the circadian cycle. The fourth aim is to use whole cell patch clamping to measure the membrane potential of SCN neurons in response to different neurochemicals at different phases of the circadian cycle.

描述(改编自申请者的摘要)：光线和其他 众所周知，刺激可以控制昼夜节律的相位。一个 特定的刺激可以推进、推迟或不影响 阶段取决于它在昼夜节律周期内的交付时间。 这些响应可以被描述为相响应曲线(PRC)。 光脉冲的PRC与暗脉冲或非PRC不同 光刺激。这项拟议的研究旨在调查 脑片中这些原癌细胞的神经和神经化学基础 一种含有视交叉上核的制剂，已知 哺乳动物的生物钟。通过采样细胞外放电速率 从许多SCN细胞在几天的过程中，昼夜节律 可以识别发射频率的节律。这次会议的主要目标是 拟议的研究是确定应用了哪些传递体物质 在体外一天中的6个不同时间段诱导相移 种群节律。 光信息被传输到SCN的一条路径是 视网膜-下丘脑束。第一个实验验证了这一假设 这种被认为是视网膜-下丘脑神经元递质的EAA， 相移就像光脉冲一样改变了SCN的种群节奏。谷氨酸， 乙酰天冬氨酸谷氨酸、天冬氨酸、N-甲基-D-天冬氨酸、喹乙醇和海人藻酸 将会受到考验。 如果获得相移，则使用受体阻滞剂来识别 突触后受体类型。根据最近的结果，组胺将 也要接受测试。从眼睛到SCN的间接途径是通过 膝间小叶，膝状体-下丘脑束(GHT) 通过刺激这一途径获得的变化模仿暗脉冲或非 光PRC。第二个实验测试了假定的发射器 GHT，即NPY、Met-Enk和GABA对相移效应的影响 SCN活动。 此外，RHT和GHT发射机将结合使用 评估这些发射机(例如，RHT)之间的相互作用 发射机可能会阻止或降低GHT发射机的影响)。 已知光脉冲可立即诱导c-fos和相关的早期 在SCN和膝间小叶中的基因，而在其他 视黄醇受体目标。 这项拟议研究的第二个目标是评估哪个发射机 物质具有诱导SCN神经元c-fos表达的能力 在试管中。我们的假设是，只有模拟 光脉冲PRC可诱导c-fos的表达。 拟议实验的第三个目标是评估 AIMS 1和AIMS 2中使用的发射机对SCN发射率的影响 神经元。神经化学药物分5个剂量，在不同的时间给药 神经元的反应可能会在整个昼夜节律中发生变化 周而复始。 第四个目标是使用全细胞膜片钳来测量 不同条件下SCN神经元膜电位的变化 生理周期不同阶段的神经化学物质。