Circadian organization is governed by extra-SCN pacemakers

Area of Science:

• Chronobiology
• Mammalian Circadian Rhythms
• Molecular Biology

Background:

• The suprachiasmatic nucleus (SCN) is the primary mammalian circadian pacemaker.
• Evidence suggests extra-SCN pacemakers, the Food Entrainable Oscillator (FEO) and Methamphetamine Sensitive Circadian Oscillator (MASCO), can drive rhythms independently of the SCN.
• These oscillators influence locomotor activity, body temperature, and endocrine functions.

Purpose of the Study:

• To investigate the role of FEO and MASCO in regulating peripheral circadian oscillators.
• To determine if extra-SCN pacemakers can influence peripheral tissues in both intact and SCN-ablated mice.
• To elucidate the phase-shifting capabilities of FEO and MASCO on peripheral tissues.

Main Methods:

• Utilized PER2::LUC mice with SCN ablation and intact controls.
• Administered methamphetamine (MA) and employed restricted feeding (RF) protocols.
• Monitored circadian rhythms and peripheral oscillator phases in various tissues (SCN, cornea, pineal, pituitary, kidney, salivary gland, lung, liver).

Main Results:

• MA administration shifted SCN, cornea, pineal, pituitary, kidney, and salivary gland phases in intact mice.
• In SCN-ablated mice, MA treatment reinstated disrupted peripheral oscillator phase relationships.
• Restricted feeding shifted cornea, pineal, kidney, salivary gland, lung, and liver phases in intact mice; in SCN-lesioned mice, all tissues aligned with mealtime.

Conclusions:

• FEO and MASCO act as potent circadian pacemakers.
• These extra-SCN pacemakers effectively regulate the phases of peripheral oscillators.
• Circadian rhythms can be driven by mechanisms outside the SCN, influenced by feeding and drugs.