Rhythmic cilia changes support SCN neuron coherence in circadian clock

Area of Science:

• Neuroscience
• Chronobiology
• Cell Biology

Background:

• The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals, coordinating physiological rhythms.
• Intercellular coupling among SCN neurons is crucial for maintaining circadian clock coherence and robustness.
• Environmental perturbations can disrupt circadian rhythms, highlighting the need for mechanisms that ensure clock stability.

Purpose of the Study:

• To investigate the role of primary cilia in intercellular coupling within the SCN.
• To determine if primary cilia in specific SCN neurons contribute to the robustness of the internal circadian clock.
• To elucidate the molecular mechanisms, including Sonic Hedgehog (Shh) signaling, by which cilia influence SCN function.

Main Methods:

• Utilized genetic ablation of ciliogenesis in neuromedin S-producing (NMS) neurons in mice.
• Assessed the impact of cilia deficiency on circadian clock phase shifting under simulated jet-lag conditions.
• Analyzed circadian rhythms of individual SCN neurons in cilia-deficient slices and investigated Sonic Hedgehog (Shh) signaling pathways.

Main Results:

• Primary cilia in NMS neurons exhibit circadian rhythmicity in abundance and length.
• Genetic ablation of cilia in NMS neurons led to rapid internal clock phase shifts under jet-lag conditions.
• SCN neurons lacking cilia showed desynchronized rhythms after external perturbations, and Shh signaling inactivation mimicked cilia ablation effects.

Conclusions:

• Primary cilia are essential for intercellular coupling among SCN neurons, ensuring robust circadian clock function.
• Rhythmic changes in cilia modulate Shh signaling and clock gene expression, contributing to circadian coherence.
• Cilia-mediated Shh signaling in the SCN is a critical mechanism for maintaining internal clock stability against environmental disruptions.