Temperature profoundly influences various life phenomena, and most animals have developed mechanisms to respond properly to environmental temperature fluctuations. To identify genes involved in sensing ambient temperature and in responding to its change, >27,000 independent P-element insertion mutants ofDrosophilawere screened. As a result, we found that defects in the genes encoding for proteins involved in histamine signaling [histidine decarboxylase (hdc), histamine-gated chloride channel subunit 1 (hisCl1), ora transientless (ort)] cause abnormal temperature preferences. The abnormal preferences shown in these mutants were restored by genetic and pharmacological rescue and could be reproduced in wild type using the histamine receptor inhibitors cimetidine and hydroxyzine. Spatial expression of these genes was observed in various brain regions including pars intercerebralis, fan-shaped body, and circadian clock neurons but not indTRPA1-expressing neurons, an essential element for thermotaxis. We also found that the histaminergic mutants showed reduced tolerance for high temperature and enhanced tolerance for cold temperature. Together, these results suggest that histamine signaling may have important roles in modulating temperature preference and in controlling tolerance of low and high temperature.

The ability to respond to environmental temperature variation is essential for survival in animals. Flies show robust temperature-preference behaviour (TPB) to find optimal temperatures. Recently, we have shown that Drosophila mushroom body (MB) functions as a center controlling TPB. However, neuromodulators that control the TPB in MB remain unknown. To identify the functions of dopamine in TPB, we have conducted various genetic studies in Drosophila. Inhibition of dopamine biosynthesis by genetic mutations or treatment with chemical inhibitors caused flies to prefer temperatures colder than normal. We also found that dopaminergic neurons are involved in TPB regulation, as the targeted inactivation of dopaminergic neurons by expression of a potassium channel (Kir2.1) induced flies with the loss of cold avoidance. Consistently, the mutant flies for dopamine receptor gene (DopR) also showed a cold temperature preference, which was rescued by MB–specific expression of DopR. Based on these results, we concluded that dopamine in MB is a key component in the homeostatic temperature control of Drosophila. The current findings will provide important bases to understand the logic of thermosensation and temperature preference decision in Drosophila. Temperature affects almost all aspects of animal development and physiological processes. The dependence of the body temperature of small insects on ambient temperature and other heat sources makes it plausible that neuronal mechanisms for sensing temperature and behavioral responses for maintaining body temperature in a permissive range must exist. By using the fruit fly model system and previously settled paradigms of temperature-preference test, we find that dopamine regulates temperature-preference behaviours. Wild-type flies show a strong temperature preference for 25°C, but inhibition of dopamine biosynthesis by genetic mutations or treatment with chemical inhibitors causes animals to prefer temperatures colder than normal. We also show that dopaminergic neurons are involved in the regulation of temperature-preference behaviours and that dopamine signalling in mushroom body neurons plays a critical role in regulating the behaviours. These results suggest that dopamine is a key component in the homeostatic temperature control of fruit flies.