Behavioural phenotypes of Dicer knockout in the mouse SCN

Area of Science:

• Neuroscience
• Chronobiology
• Molecular Biology

Background:

• The suprachiasmatic nucleus (SCN) governs circadian rhythms, anticipating environmental light-dark cycles.
• MicroRNAs (miRNAs) are known post-transcriptional regulators involved in SCN physiology.
• The impact of a complete loss of mature miRNAs on SCN function remained unexplored.

Purpose of the Study:

• To investigate the behavioral consequences of miRNA depletion specifically within the SCN.
• To determine the role of mature miRNAs in maintaining robust circadian oscillations and SCN output.

Main Methods:

• Generation of a mouse model with Dicer inactivated in the SCN (Syt10^Cre x Dicer^flox).
• Analysis of circadian period length and rhythm precision in knockout mice under light-dark and constant darkness conditions.
• Assessment of behavioral rhythms following targeted Dicer recombination in the SCN via Cre delivery.

Main Results:

• Complete miRNA loss in the SCN significantly shortened circadian period length (~37 min tissue, ~45 min activity).
• Mice lacking SCN miRNAs showed reduced rhythm precision and increased activity onset variability.
• Some animals developed ultradian rhythms under constant light, and partial miRNA loss impacted rhythmicity.

Conclusions:

• MicroRNAs are essential for physiological SCN function.
• miRNAs play a pivotal role in ensuring the robustness and precision of circadian oscillations.
• This study underscores the importance of the miRNome for regulating biological timing.