Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila

描述（由申请人提供）：生物钟调节生活的许多方面，包括睡眠、活动和体温 (BTR) 节律。我们最近发现了一种新的果蝇昼夜节律输出，即温度偏好节律（TPR），其中果蝇更喜欢白天温度升高和夜间温度下降。我们最近发表的数据表明，果蝇 TPR 与哺乳动物 BTR 具有相同的特征。果蝇是变温动物，通常通过行为调节体温。因此，寻找首选温度是调节果蝇体温的策略。果蝇大脑中的生物钟细胞与哺乳动物 SCN（视交叉上核）神经元的功能同源。我们发现一小群昼夜节律神经元，即背侧神经元 2（DN2），特异性调节 TPR，但不调节运动活动，这表明 TPR 和运动活动是通过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。该提案的目标是定义神经肽如何调节 TPR 以及热感觉神经元如何对 TPR 做出贡献。我们发现，运动活动的关键神经肽 PDF（色素分散因子）并不参与 TPR，而神经肽 DH31（利尿激素 31）、其受体 DH31R 和 PDFR 以及关键时钟神经元 DN2 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感觉神经元对于 TPR 至关重要。在目标 3 中，我们将确定热感觉神经元是否参与神经元网络，控制 TPR。

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.