Anticipatory Capture of Circulating Peptidergic Vesicles in a Clock Neuron

Mar 11, 2026Molecular biology of the cell

Early Collection of Signaling Protein Packages by a Brain Clock Cell

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Abstract

Neuropeptide-containing dense-core vesicles (DCVs) in sLNv terminals accumulate rhythmically, with late-night increases preceding midmorning release.

Neuropeptide release by sLNv clock neurons is linked to circadian behaviors and sleep.
DCVs are transported in both directions within the axon, indicating that they circulate.
No increase in the delivery of DCVs to terminals occurs throughout the day.
The daily boost in neuropeptide content at terminals results from capturing circulating DCVs.
This capture happens before the increase in neuronal activity and is not influenced by certain signaling pathways.
A mutation in a clock gene disrupts the rhythmic capture of DCVs.

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Neuropeptide release bysLNv clock neurons controls circadian behaviors and sleep. Strikingly, 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 thebrain explant preparation. First, post-exocytosis DCV axonal transport and presynaptic 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 independent of concurrent IPsignaling and axon arbor expansion. Finally, aclock gene mutation inhibits rhythmic DCV capture. Thus, rather than responding to Casignaling or axonal plasticity, capture of circulating DCVs in sLNv presynapses is increased by the molecular clock in anticipation of activity-induced release hours later. [Media: see text]. Drosophila ex vivo per2+ 2+ 3

Anticipatory Capture of Circulating Peptidergic Vesicles in a Clock Neuron

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