Desynchronized Somas and Terminals in a Morning Clock Neuron: Presynaptic Ca 2+ Spiking and Native Neuropeptide Release Peak As Somatic Ca 2+ Declines

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Summary Drosophila sLNv clock neurons release the co-packaged neuropeptides PDF and sNPF to regulate circadian behaviors (e.g., morning anticipation) and nighttime sleep 1-3 . Previous studies of membrane potential and cytoplasmic Ca 2+ at the soma suggested that sLNv neuron activity peaks at night 4,5 , but exocytosis of neuropeptide-containing dense-core vesicles (DCVs) at their terminals peaks hours later at midmorning 6 . To resolve the basis of the timing mismatch between somatic physiology and terminal exocytosis, recently developed probes were used to measure daily rhythms in sLNv neuron synaptic Ca 2+ and sNPF release. Remarkably, at midmorning after soma Ca 2+ has dropped, both Ca 2+ spiking and clock-dependent native neuropeptide release peak in the distal terminals of the protocerebrum. Furthermore, Ca 2+ in the soma and terminals differ in dependence on Ca 2+ influx. Finally, synaptic DCV exocytosis requires Ca 2+ spike activity at terminals that is not evident at the soma. These results lead to two striking conclusions. First, soma Ca 2+ recording, which is the focus of many circuit studies, is not indicative of presynaptic Ca 2+ and neuropeptide release in distal sLNv terminals. Second, daily clock- and activity-dependent sLNv terminal neuropeptide release occurs ∼9-18 hours in advance of known sLNv neuropeptide effects on nighttime sleep and morning behavior.