A direct SCN-to-DMH output pathway organizes circadian behavioral timing

Area of Science:

• Neuroscience
• Chronobiology
• Molecular Biology

Background:

• Circadian rhythms govern daily behaviors, originating in the suprachiasmatic nucleus (SCN).
• The dorsomedial hypothalamus (DMH) is involved in circadian output, but its precise role in relaying SCN timing is unclear.
• Distinguishing between local DMH timekeeping and SCN-derived signals is crucial for understanding behavioral rhythm organization.

Purpose of the Study:

• To define and test a direct SCN-to-DMH neural pathway responsible for transmitting circadian timing signals.
• To investigate whether the DMH relies on local molecular clocks or SCN input for behavioral rhythmicity.

Main Methods:

• Combined DMH neuronal ablation and local clock gene (Cry1/2) disruption.
• Utilized retrograde and intersectional tracing techniques.
• Performed single-cell RNA sequencing and optogenetic stimulation of SCN neurons.

Main Results:

• DMH neuronal ablation disrupted locomotor rhythms, while disrupting DMH molecular clocks did not.
• Identified a sparse population of DMH-projecting SCN neurons, distinct from known AVP and VIP populations.
• Optogenetic activation of these SCN neurons organized locomotor rhythms and induced phase shifts.

Conclusions:

• Intact DMH neurons, rather than local molecular clocks, are essential for maintaining locomotor rhythmicity.
• A specific, molecularly defined subset of SCN neurons directly projects to the DMH to organize circadian behavior.
• This SCN-DMH pathway is a key regulator of circadian locomotor timing.