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.

Public Health Relevance

Mammalian BTR is critical for sustaining functions that maintain homeostasis, such as sleep. The underlying mechanisms of the sleep disorders and BTR remain unknown, although they greatly impact human health. Using Drosophila as a model has contributed to the discovery of many genes and mechanisms crucial for circadian clock and sleep that are conserved between flies and humans. Thus, studying TPR might expand our understanding of fundamental BTR and facilitate the characterization of sleep mechanisms. PUBLIC HEALTH RELEVANCE: This proposal has high clinical relevance because understanding circadian rhythm is important for understanding the aspects of human physiology, including sleep and metabolic energy usage. Our recently published data suggest that fly TPR shares features with mammalian BTR. Therefore, understanding the mechanisms of fly TPR should ultimately expand the current understanding of mammalian BTR, sleep disorders, and general sleep-associated issues, such as jet lag or sleep disturbances in night-shift workers.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM107582-01
Application #
8558937
Study Section
Neurodifferentiation, Plasticity, and Regeneration Study Section (NDPR)
Program Officer
Sesma, Michael A
Project Start
2013-09-01
Project End
2018-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$286,672
Indirect Cost
$96,672
Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229
Goda, Tadahiro; Leslie, Jennifer R; Hamada, Fumika N (2014) Design and analysis of temperature preference behavior and its circadian rhythm in Drosophila. J Vis Exp :e51097