Anticipatory Capture of Circulating Peptidergic Vesicles in a Clock Neuron

Nov 24, 2025bioRxiv : the preprint server for biology

Clock Neurons Prepare to Capture Circulating Peptide-Carrying Vesicles

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Abstract

Neuropeptide-containing dense-core vesicles (DCVs) circulate in sLNv clock neuron terminals, contributing to rhythmic neuropeptide release.

Neuropeptide content in sLNv terminals accumulates rhythmically, peaking late at night.
The increase in neuropeptide content is linked to the capture of circulating DCVs, not increased delivery to terminals.
Constant anterograde transport of DCVs occurs throughout the day, indicating no rise in delivery rates.
Capture of DCVs happens prior to the daily increase in neuronal activity and is unaffected by specific signaling pathways.
A mutation in the clock gene disrupts the rhythmic capture of DCVs.

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Neuropeptide release bysLNv clock neurons controls circadian behaviors and sleep. Remarkably, neuropeptide content in sLNv terminals is rhythmic with late-night accumulation occurring while the axon arbor is expanding in preparation for midmorning synaptic exocytosis of neuropeptide-containing dense-core vesicles (DCVs). Past studies showed increased synaptic neuropeptide content can be produced by delivery of more neuropeptide to terminals or activity-dependent capture of circulating DCVs. To distinguish between these mechanisms, neuropeptide-containing DCVs were imaged in the living brain explant. First, post-exocytosis DCV axonal transport and synaptic neuropeptide accumulation following retrograde transport inhibition show that sLNv DCVs circulate. Furthermore, anterograde transport to terminals is constant throughout the day demonstrating there is no increase in DCV delivery. Rather, capture of circulating DCVs produces the daily boost in terminal neuropeptide content. Remarkably, this capture occurs before the daily increase in Caspike activity and is also independent of concurrent IPsignaling and daily axon arbor expansion. Finally, aclock gene mutation inhibits rhythmic DCV capture. Thus, rather than participating in axonal plasticity or responding to Casignaling, capture of circulating DCVs in sLNv presynapses is increased by the molecular clock in anticipation of activity-induced release hours later. Drosophila per2+ 2+ 3

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Anticipatory Capture of Circulating Peptidergic Vesicles in a Clock Neuron

Abstract

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