权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular and Neural Mechanisms of Temperature Preference Rhythm in Drosophila

果蝇温度偏好节律的分子和神经机制

基本信息

批准号：
10426451
负责人：
Fumika Hamada
金额：
$ 22.52万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10426451
关键词：
Antibodies Behavior Behavioral Body Temperature Brain Calcitonin Receptor Calcium Cells Circadian Rhythms Cyclic AMP Data Diuretics Dorsal Drosophila genus Exhibits Fc Receptor Genetic Goals Grant Homeostasis Homologous Gene Hormones Human Human body Image In Vitro Infrastructure Jet Lag Syndrome Knockout Mice Lead Ligands Mammals Measurement Mediating Mediator of activation protein Messenger RNA Metabolic Metabolism Molecular Monitor Motor Activity Mus Neurons Outcome Outcome Study Output Periodicity Peripheral Physiology Pigments Play Protein Family Proteins Reverse Transcriptase Polymerase Chain Reaction Role Sleep Sleep Disorders Sleep disturbances Synapses Temperature Testing Time Wakefulness circadian circadian pacemaker expectation experimental study fly high resolution imaging insight knock-down mutant neural circuit neuromechanism novel preference receptor reconstitution shift work

项目摘要

Human body temperature increases during wakefulness and decreases during sleep. The body temperature rhythm (BTR) is a robust output of the circadian clock and is fundamental for maintaining homeostasis, such as generating metabolic energy and sleep, as well as entraining peripheral clocks in mammals. However, the mechanisms that regulate BTR are largely unknown. Therefore, there is a crucial need to identify the molecular mechanisms that regulate BTR. Drosophila are ectotherms, and their body temperatures are close to ambient temperature; therefore, flies select a preferred environmental temperature to set their body temperature. We identified a novel circadian output, the temperature preference rhythm (TPR), in which the preferred temperature in flies increases during the day and decreases at night. TPR thereby produces a daily body temperature rhythm. Fly TPR shares many features with mammalian BTR. During the current grant term, we established that Diuretic hormone 31 receptor (DH31R), a Drosophila calcitonin receptor family protein, mediates TPR, and we demonstrated that the closest mouse homolog of DH31R, calcitonin receptor (Calcr), is essential for normal BTR in mice. Importantly, both TPR and BTR are regulated in a distinct manner from locomotor activity rhythms, and neither DH31R nor Calcr regulate locomotor activity rhythms. Together, our findings suggest that DH31R/Calcr is an ancient and specific mediator of BTR. Thus, understanding fly TPR will provide fundamental insights into the molecular and neural mechanisms that control BTR in mammals. The goal of this proposal is to determine the molecular and neural mechanisms of TPR. Our recent study suggests that DH31 acts on clock neurons via DH31R to regulate TPR. Although DH31 primarily activates DH31R, DH31 can also activate the Pigment dispersing factor receptor (PDFR), required for locomotor activity rhythms, at a modest level in vitro. Because PDFR does not play a major role in daytime TPR, we expect that DH31R and PDFR are expressed in different cells. In addition to the identification of crucial ligand-receptor interactions, we recently found that master clock cells, the dorsal clock neurons 2 (DN2s), control TPR but not locomotor activity rhythms. The central hypothesis of this proposal: DN2s have temporally-regulated contacts with DN1ps and control rhythmic expression of DH31, which activates DH31R in PDFR-negative DN1ps, resulting in TPR. In Aim 1, we will elucidate the physical and functional relationship between DN1ps and DN2s to control TPR. In Aim 2, we will determine the mechanism that sets rhythmic DH31 expression in DN1ps. In Aim 3, we will determine the mechanism by which DH31R-expressing neurons control TPR. This project will contribute to a mechanistic understanding of fly TPR. The outcomes of this study should ultimately provide a novel mechanistic understanding of the mammalian BTR.

人的体温在清醒时升高，在睡眠时降低。的