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Bulgari, D.

Publications and source records attributed to Bulgari, D..

2 recordsLinked to original sources

Adult Clock Neuron Somatic Neuropeptide Release and Cytonemes Regulate Sleep

Drosophila s-LNv clock neurons promote nighttime sleep by releasing the neuropeptide sNPF to activate sNPF receptors (sNPF-Rs) on l-LNv clock neurons. Behavior is controlled by synaptic transmission, but s-LNv and l-LNv neurons are not connected directly by chemical synapses. To investigate the basis of sNPF/sNPF-R communication between LNv neurons, the spread of sNPF was imaged in the adult brain. We report the daily midmorning burst of sNPF released from s-LNv terminals does not reach l-LNv neurons or s-LNv somata. Instead, sNPF released by the s-LNv soma late at night in response to sleep-promoting IP3 signaling reaches l-LNv somata, but not their terminals. In addition to communication by neuropeptide diffusion, analysis of fly connectomes revealed that adult s-LNv and l-LNv neurons form non-synaptic direct contacts mediated by cytonemes. Remarkably, genetically perturbing LNv neuron cytonemes alters sleep latency, but not nighttime sleep, the target of somatic sNPF release, or circadian behavior, which depends on PDF neuropeptide released by LNv terminals. Therefore, three distinct aspects of adult rhythmic behavior are produced by terminals, the soma and cytonemes, with the latter possibly acting via contacts that are not currently annotated in the connectome.

neuroscience↗

Release of large synaptic DCV proteins is triggered by Ca2+-independent Rugose-localized complexin phosphorylation

Neuronal dense-core vesicles (DCVs) contain neuropeptides and much larger proteins that affect synaptic growth and plasticity. Rather than using full collapse exocytosis that is common in endocrine cells, DCVs at a native intact synapse, the Drosophila neuromuscular junction, release their contents via fusion pores formed by kiss and run exocytosis. Here fluorogen activating protein (FAP) imaging reveals the permeability range of synaptic DCV fusion pores and then shows that this constraint is circumvented by cAMP-induced extra fusions with dilating pores that result in DCV emptying. These Ca2+-independent full fusions require PKA-R2, a PKA phosphorylation site on the fusion clamp protein complexin and the acute presynaptic function of Rugose/Neurobeachin, a PKA-R2 anchor implicated in learning and autism. Therefore, localized Ca2+-independent cAMP signaling opens dilating fusion pores to release large cargo proteins that cannot pass through the narrower fusion pores that normally dominate spontaneous and Ca2+-evoked synaptic protein release. Hence, two independent exocytosis triggers (Ca2+ and cAMP) vary the composition of released proteins at the synapse by differentially adjusting DCV fusion pores.

neuroscience↗