Timed exercise modulates inter-coupling strength between evening and morning oscillators in mice

Area of Science:

• Chronobiology
• Animal Behavior
• Circadian Rhythms

Background:

• The circadian system relies on coupled oscillators, typically the evening (E) and morning (M) oscillators.
• Understanding how external stimuli modulate inter-oscillator coupling is crucial for circadian rhythm regulation.
• Exercise is a known modulator of circadian rhythms, but its specific effects on oscillator coupling remain unclear.

Purpose of the Study:

• To investigate the impact of timed daily exposure to a novel cage with a running wheel (NCRW) on circadian oscillator coupling in nocturnal rodents.
• To determine if the timing of NCRW exposure (ZT12 vs. ZT21) differentially affects circadian behavioral rhythms and inter-oscillator coupling strength.

Main Methods:

• Adult male C57BL/6 mice were exposed to NCRW for 3 hours daily for three weeks at either ZT12 (early dark) or ZT21 (late dark).
• Circadian rhythms were assessed by measuring the free-running period in constant darkness (DD).
• Reentrainment rates to an 8-hour phase advance of the light-dark (LD) cycle and phase shifts induced by a single advanced LD cycle were analyzed.

Main Results:

• Exposure to NCRW at ZT12 shortened the free-running period and accelerated reentrainment of activity onset.
• Exposure to NCRW at ZT21 lengthened the free-running period and decelerated reentrainment of activity onset.
• ZT12 NCRW exposure enhanced coupling of the E oscillator to the M oscillator, while ZT21 exposure enhanced M to E oscillator coupling.

Conclusions:

• Timed exercise, specifically NCRW exposure, phase-dependently modulates inter-oscillator coupling strengths in nocturnal rodents.
• The timing of exercise is critical in determining its effects on circadian rhythm regulation, including activity onset and offset.
• These findings highlight exercise as a potent zeitgeber capable of fine-tuning the internal circadian clock's coordination.