Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila

描述(申请人提供)：生物钟调节生活的许多方面，包括睡眠、活动和体温(BTR)节奏。我们最近发现了一种新的果蝇昼夜节律输出，温度偏好节律(TPR)，在这种节律中，果蝇喜欢白天温度上升，晚上下降。我们最近发表的数据表明，Fly TPR与哺乳动物的BTR具有相同的特征。果蝇是一种外温动物，通常通过调节体温行为来调节体温。因此，寻找合适的温度是调节苍蝇体温的策略。苍蝇脑中的昼夜节律时钟细胞是哺乳动物视交叉上核(SCN)神经元的功能同源物。我们发现，一小群昼夜节律神经元，背神经元2S(DN2S)，特异性地调节TPR，但不调节运动活动，表明TPR和运动活动是由不同的昼夜节律神经元控制的。因此，了解TPR将为控制昼夜节律的分子和神经机制提供新的见解。这项提案的目标是定义神经肽如何调节TPR以及热敏神经元如何参与TPR。我们发现，运动活动的关键神经肽PDF(色素分散因子)不参与TPR，而DH31(利尿激素31)、其受体DH31R和PDFR以及关键时钟神经元DN2S是正常TPR所必需的。在目标1中，我们将阐明DH31调节TPR的机制。在目标2中，我们将研究DN2调节TPR的机制。此外，我们的初步数据表明，热敏神经元对TPR至关重要。在目标3中，我们将确定热敏神经元是否参与控制TPR的神经元网络。

DESCRIPTION (provided by applicant): The circadian clock regulates many aspects of life, including sleep and activity and body temperature (BTR) rhythms. We recently identified a novel Drosophila circadian output, temperature preference rhythm (TPR), in which the flies preferred rises in temperature during the day and falls during the night. Our recently published data suggest that fly TPR shares features with mammalian BTR. Drosophila are ectotherms, which typically regulate body temperature behaviorally. Therefore, seeking a preferred temperature is the strategy used to regulate the body temperatures of flies. The circadian clock cells in the fly brain are functional homologs of mammalian SCN (Suprachiasmatic nucleus) neurons. We showed that a small group of circadian neurons, the dorsal neuron 2s (DN2s), specifically regulate TPR, but not locomotor activity, indicating that TPR and locomotor activity are controlled through distinct circadian neurons. Therefore, understanding the TPR will provide new insights into the molecular and neural mechanisms controlling circadian rhythms. The goal of this proposal is to define how neuropeptides regulate TPR and how thermosensory neurons contribute to TPR. We found that PDF (Pigment Dispersing Factor), a critical neuropeptide for locomotor activity, is not involved in TPR, whereas the neuropeptide, DH31 (Diuretic Hormone 31), its receptors DH31R and PDFR and the key clock neurons, DN2s, are necessary for normal TPR. In Aim 1, we will elucidate the mechanisms by which DH31 regulates TPR. In Aim 2, we will examine the mechanisms by which DN2s regulate TPR. Furthermore, our preliminary data suggests that thermosensory neurons are critical for TPR. In Aim 3, we will determine whether thermosensory neurons participate in the neuronal network, controlling TPR.