APA
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Bulgari, D., Deitcher, D., Schmidt, B., Carpenter, M. A., Szent‐Gyorgyi, C., Bruchez, M., & Levitan, E. (2019). Activity-evoked and spontaneous opening of synaptic fusion pores. Proceedings of the National Academy of Sciences of the United States of America.
Chicago/Turabian
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Bulgari, Dinara, D. Deitcher, B. Schmidt, M. A. Carpenter, C. Szent‐Gyorgyi, M. Bruchez, and E. Levitan. “Activity-Evoked and Spontaneous Opening of Synaptic Fusion Pores.” Proceedings of the National Academy of Sciences of the United States of America (2019).
MLA
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Bulgari, Dinara, et al. “Activity-Evoked and Spontaneous Opening of Synaptic Fusion Pores.” Proceedings of the National Academy of Sciences of the United States of America, 2019.
BibTeX Click to copy
@article{dinara2019a,
title = {Activity-evoked and spontaneous opening of synaptic fusion pores},
year = {2019},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
author = {Bulgari, Dinara and Deitcher, D. and Schmidt, B. and Carpenter, M. A. and Szent‐Gyorgyi, C. and Bruchez, M. and Levitan, E.}
}
Significance Neuropeptides are released at synapses to regulate mood and behaviors. Using an imaging approach, formation of neuropeptide-conductive fusion pores are detected at intact native synapses. Surprisingly, it is discovered that these fusion pores open occasionally even when the synapse is not electrically active. These spontaneous events are mechanistically different from the fusion pore opening that is evoked typically by bursts of activity. Spontaneous opening of fusion pores constitutes a mechanism for basal synaptic transmission by neuropeptides even when synapses are electrically silent. Synaptic release of neuropeptides packaged in dense-core vesicles (DCVs) regulates synapses, circuits, and behaviors including feeding, sleeping, and pain perception. Here, synaptic DCV fusion pore openings are imaged without interference from cotransmitting small synaptic vesicles (SSVs) with the use of a fluorogen-activating protein (FAP). Activity-evoked kiss and run exocytosis opens synaptic DCV fusion pores away from active zones that readily conduct molecules larger than most native neuropeptides (i.e., molecular weight [MW] up to, at least, 4.5 kDa). Remarkably, these synaptic fusion pores also open spontaneously in the absence of stimulation and extracellular Ca2+. SNARE perturbations demonstrate different mechanisms for activity-evoked and spontaneous fusion pore openings with the latter sharing features of spontaneous small molecule transmitter release by active zone-associated SSVs. Fusion pore opening at resting synapses provides a mechanism for activity-independent peptidergic transmission.