A Novel Pathway for Sensory-Mediated Arousal Involves Splicing of an Intron in theperiodClock Gene

Oct 18, 2014Sleep

A new sensory arousal pathway involves editing a part of the body clock gene

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Abstract

Increased dmpi8 splicing efficiency is associated with longer arousal durations in Drosophila following sensory stimuli.

Changes in dmpi8 splicing influence daytime activity levels without direct involvement of the circadian clock gene period.
Higher dmpi8 splicing efficiency in genetically altered flies results in prolonged arousal after exposure to light and mechanical stimulation.
Thermal regulation of dmpi8 splicing may function as a mechanism to adjust sensory arousal, especially during warm temperatures.
On hot days, inefficient splicing of the dmpi8 intron appears to promote quiescence in flies by reducing sensory-mediated arousal.

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STUDY OBJECTIVES: D. melanogaster is an excellent animal model to study how the circadian (≅24-h) timing system and sleep regulate daily wake-sleep cycles. Splicing of a temperature-sensitive 3'-terminal intron (termed dmpi8) from the circadian clock gene period (per) regulates the distribution of daily activity in Drosophila. The role of dmpi8 splicing on daily behavior was further evaluated by analyzing sleep.

DESIGN: Transgenic flies of the same genetic background but expressing either a wild-type recombinant per gene or one where the efficiency of dmpi8 splicing was increased were exposed to different temperatures in daily light-dark cycles and sleep parameters measured. In addition, transgenic flies were briefly exposed to a variety of sensory-mediated stimuli to measure arousal responses.

RESULTS: Surprisingly, we show that the effect of dmpi8 splicing on daytime activity levels does not involve a circadian role for per but is linked to adjustments in sensory-dependent arousal and sleep behavior. Genetically altered flies with high dmpi8 splicing efficiency remain aroused longer following short treatments with light and non-photic cues such as mechanical stimulation.

CONCLUSIONS: We propose that the thermal regulation of dmpi8 splicing acts as a temperature-calibrated rheostat in a novel arousal mechanism, so that on warm days the inefficient splicing of the dmpi8 intron triggers an increase in quiescence by decreasing sensory-mediated arousal, thus ensuring flies minimize being active during the hot midday sun despite the presence of light in the environment, which is usually a strong arousal cue for diurnal animals.

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A Novel Pathway for Sensory-Mediated Arousal Involves Splicing of an Intron in theperiodClock Gene

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