Anticipatory Capture of Circulating Peptidergic Vesicles in a Clock Neuron

Area of Science:

• Neuroscience
• Chronobiology
• Cell Biology

Background:

• * *Drosophila* sLNv clock neurons regulate circadian rhythms and sleep through neuropeptide release.
• * Neuropeptide accumulation in sLNv terminals is rhythmic, preceding synaptic exocytosis.
• * Previous studies suggested neuropeptide levels increase via enhanced delivery or capture of circulating dense-core vesicles (DCVs).

Purpose of the Study:

• * To differentiate between neuropeptide delivery and DCV capture mechanisms in *Drosophila* sLNv neurons.
• * To investigate the regulation of synaptic neuropeptide content by the circadian clock.

Main Methods:

• * Live imaging of neuropeptide-containing DCVs in *Drosophila* brain explants.
• * Inhibition of retrograde transport to assess DCV circulation.
• * Analysis of DCV transport dynamics and accumulation in relation to neuronal activity and clock gene function.

Main Results:

• * *Drosophila* sLNv DCVs were observed to circulate and undergo axonal transport.
• * Anterograde transport of DCVs to terminals remained constant, indicating no increased delivery.
• * Rhythmic capture of circulating DCVs, not increased delivery, accounts for daily neuropeptide accumulation.
• * DCV capture precedes increased Ca²⁺ activity and is independent of IP₃ signaling and axon arbor expansion.
• * A *per* clock gene mutation disrupted rhythmic DCV capture.

Conclusions:

• * Synaptic neuropeptide content in *Drosophila* sLNv neurons is regulated by the rhythmic capture of circulating DCVs.
• * This capture mechanism is controlled by the molecular clock, anticipating future release.
• * DCV capture is independent of axonal plasticity and Ca²⁺ signaling, highlighting a distinct clock-controlled presynaptic process.