ABSTRACT Synapses require resources synthesized in the neuronal soma, but there are no known mechanisms to overcome delays associated with the synthesis and axonal transport of new proteins

generated in response to activity, or to direct resources specifically to active synapses. Here, _in vivo_ imaging of the _Drosophila melanogaster_ neuromuscular junction reveals a

cell-biological strategy that addresses these constraints. Peptidergic vesicles continually transit through resting terminals, but retrograde peptidergic vesicle flux is accessed following

activity to rapidly boost neuropeptide content in synaptic boutons. The presence of excess transiting vesicles implies that synaptic neuropeptide stores are limited by the capture of

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support SIMILAR CONTENT BEING VIEWED BY OTHERS DETERMINANTS OF SYNAPSE DIVERSITY REVEALED BY SUPER-RESOLUTION QUANTAL TRANSMISSION AND ACTIVE ZONE IMAGING Article Open access 11 January 2022

SYNAPTIC VESICLE TRAFFIC IS SUPPORTED BY TRANSIENT ACTIN FILAMENTS AND REGULATED BY PKA AND NO Article Open access 21 October 2020 THE ENDOSOMAL Q-SNARE, SYNTAXIN 7, DEFINES A RAPIDLY

REPLENISHING SYNAPTIC VESICLE RECYCLING POOL IN HIPPOCAMPAL NEURONS Article Open access 18 August 2021 REFERENCES * Zupanc, G.K. Peptidergic transmission: from morphological correlates to

functional implications. _Micron_ 27, 35–91 (1996). Article  CAS  PubMed  Google Scholar  * Burbach, J.P., Luckman, S.M., Murphy, D. & Gainer, H. Gene regulation in the magnocellular

hypothalamo-neurohypophysial system. _Physiol. Rev._ 81, 1197–1267 (2001). Article  CAS  PubMed  Google Scholar  * Taghert, P.H. & Veenstra, J.A. _Drosophila_ neuropeptide signaling.

_Adv. Genet._ 49, 1–65 (2003). Article  CAS  PubMed  Google Scholar  * Nassel, D.R. Neuropeptides in the nervous system of _Drosophila_ and other insects: multiple roles as neuromodulators

and neurohormones. _Prog. Neurobiol._ 68, 1–84 (2002). Article  PubMed  Google Scholar  * Ahmari, S.E., Buchanan, J. & Smith, S.J. Assembly of presynaptic active zones from cytoplasmic

transport packets. _Nat. Neurosci._ 3, 445–451 (2000). Article  CAS  PubMed  Google Scholar  * Zhai, R.G. et al. Assembling the presynaptic active zone: a characterization of an active zone

precursor vesicle. _Neuron_ 29, 131–143 (2001). Article  CAS  PubMed  Google Scholar  * Lessmann, V., Gottmann, K. & Malcangio, M. Neurotrophin secretion: current facts and future

prospects. _Prog. Neurobiol._ 69, 341–374 (2003). Article  CAS  PubMed  Google Scholar  * Pierce, J.P. & Milner, T.A. Parallel increases in synaptic and surface areas of mossy fiber

terminals following seizure induction. _Synapse_ 39, 249–256 (2001). Article  CAS  PubMed  Google Scholar  * Murthy, V.N., Schikorski, T., Stevens, C.F. & Zhu, Y. Inactivity produces

increases in neurotransmitter release and synapse size. _Neuron_ 32, 673–682 (2001). Article  CAS  PubMed  Google Scholar  * Brown, A. Axonal transport of membranous and nonmembranous

cargoes: a unified perspective. _J. Cell Biol._ 160, 817–821 (2003). Article  CAS  PubMed  PubMed Central  Google Scholar  * Shakiryanova, D., Tully, A., Hewes, R.S., Deitcher, D.L. &

Levitan, E.S. Activity-dependent liberation of synaptic neuropeptide vesicles. _Nat. Neurosci._ 8, 173–178 (2005). Article  CAS  PubMed  Google Scholar  * Rao, S., Lang, C., Levitan, E.S.

& Deitcher, D.L. Visualization of neuropeptide expression, transport, and exocytosis in _Drosophila melanogaster_. _J. Neurobiol._ 49, 159–172 (2001). Article  CAS  PubMed  Google

Scholar  * Heifetz, Y. & Wolfner, M.F. Mating, seminal fluid components, and sperm cause changes in vesicle release in the _Drosophila_ female reproductive tract. _Proc. Natl. Acad. Sci.

USA_ 101, 6261–6266 (2004). Article  CAS  PubMed  PubMed Central  Google Scholar  * Husain, Q.M. & Ewer, J. Use of targetable GFP-tagged neuropeptide for visualizing neuropeptide

release following execution of a behavior. _J. Neurobiol._ 59, 181–191 (2004). Article  CAS  PubMed  Google Scholar  * Mudher, A. et al. GSK-3β inhibition reverses axonal transport defects

and behavioural phenotypes in _Drosophila_. _Mol. Psych._ 9, 522–530 (2004). Article  CAS  Google Scholar  * Sturman, D.A, Shakiryanova, D., Hewes, R.S., Deitcher, D.L. & Levitan, E.S.

Nearly neutral secretory vesicles in _Drosophila_ nerve terminals. _Biophys. J._ 90, L45–L47 (2006). Article  CAS  PubMed  PubMed Central  Google Scholar  * Atwood, H.L., Govind, C.K. &

Wu, C.F. Differential ultrastructure of synaptic terminals on ventral longitudinal abdominal muscles in _Drosophila_ larvae. _J. Neurobiol._ 24, 1008–1024 (1993). Article  CAS  PubMed 

Google Scholar  * Jia, X.X., Gorczyca, M. & Budnik, V. Ultrastructure of neuromuscular junctions in _Drosophila_: comparison of wild type and mutants with increased excitability. _J.

Neurobiol._ 24, 1025–1044 (1993). Article  CAS  PubMed  PubMed Central  Google Scholar  * Levitan, E.S. Studying neuronal peptide release and secretory granule dynamics with green

fluorescent protein. _Methods_ 16, 182–187 (1998). Article  CAS  PubMed  Google Scholar  * Krueger, S.R., Kolar, A. & Fitzsimonds, R.M. The presynaptic release apparatus is functional in

the absence of dendritic contact and highly mobile within isolated axons. _Neuron_ 40, 945–957 (2003). Article  CAS  PubMed  Google Scholar  * Darcy, K.J., Staras, K., Collinson, L.M. &

Goda, Y. Constitutive sharing of recycling synaptic vesicles between presynaptic boutons. _Nat. Neurosci._ 9, 315–321 (2006). Article  CAS  PubMed  Google Scholar  * Neubig, R. The time

course of drug action. in _Principles of Drug Action_. 3rd edn. (eds. Pratt, W.B. & Taylor, P.) 311–313 (Churchill-Livingstone, London, 1990). Google Scholar  Download references

ACKNOWLEDGEMENTS We thank W.C. DeGroat and K. Kandler for their comments. This research was supported by grant NS32385 from the US National Institutes of Health to E.S.L. AUTHOR INFORMATION

Author notes * Arvonn Tully Present address: Compix Inc., 109 Nicholson Road, Cranberry, Pennsylvania, 15143, USA AUTHORS AND AFFILIATIONS * Department of Pharmacology, University of

Pittburgh, Pittsburgh, Pennsylvania, 15261, USA Dinara Shakiryanova, Arvonn Tully & Edwin S Levitan Authors * Dinara Shakiryanova View author publications You can also search for this

author inPubMed Google Scholar * Arvonn Tully View author publications You can also search for this author inPubMed Google Scholar * Edwin S Levitan View author publications You can also

search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Edwin S Levitan. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial

interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIG. 1 Constitutive replacement of synaptic DCVs is slow. (PDF 137 kb) SUPPLEMENTARY FIG. 2 Detection of vesicle shipments. (PDF 73 kb)

SUPPLEMENTARY FIG. 3 Movement of vesicle shipments. (PDF 189 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Shakiryanova, D., Tully, A. &

Levitan, E. Activity-dependent synaptic capture of transiting peptidergic vesicles. _Nat Neurosci_ 9, 896–900 (2006). https://doi.org/10.1038/nn1719 Download citation * Received: 31 March

2006 * Accepted: 18 May 2006 * Published: 11 June 2006 * Issue Date: 01 July 2006 * DOI: https://doi.org/10.1038/nn1719 SHARE THIS ARTICLE Anyone you share the following link with will be

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