Synaptic vesicles transiently dock to refill release sites.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
17
04
2020
accepted:
01
09
2020
pubmed:
30
9
2020
medline:
16
1
2021
entrez:
29
9
2020
Statut:
ppublish
Résumé
Synaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must 'dock' to refill vacated release sites. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation, then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone. Fusions during synchronous release are distributed throughout the active zone, whereas fusions during asynchronous release are biased toward the center of the active zone. After stimulation, the total number of docked vesicles across all synapses decreases by ~40%. Within 14 ms, new vesicles are recruited and fully replenish the docked pool, but this docking is transient and they either undock or fuse within 100 ms. These results demonstrate that the recruitment of synaptic vesicles to release sites is rapid and reversible.
Identifiants
pubmed: 32989294
doi: 10.1038/s41593-020-00716-1
pii: 10.1038/s41593-020-00716-1
pmc: PMC8054220
mid: NIHMS1625719
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1329-1338Subventions
Organisme : NINDS NIH HHS
ID : R01 NS105810
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007445
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026445
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS034307
Pays : United States
Organisme : NINDS NIH HHS
ID : R25 NS063307
Pays : United States
Organisme : NINDS NIH HHS
ID : DP2 NS111133
Pays : United States
Références
Heuser, J. E. et al. Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J. Cell Biol. 81, 275–300 (1979).
pubmed: 38256
Kaeser, P. S. & Regehr, W. G. The readily releasable pool of synaptic vesicles. Curr. Opin. Neurobiol. 43, 63–70 (2017).
pubmed: 28103533
pmcid: 5447466
Schikorski, T. & Stevens, C. F. Quantitative ultrastructural analysis of hippocampal excitatory synapses. J. Neurosci. 17, 5858–5867 (1997).
pubmed: 9221783
pmcid: 6573206
Imig, C. et al. The morphological and molecular nature of synaptic vesicle priming at presynaptic active zones. Neuron 84, 416–431 (2014).
pubmed: 25374362
Hammarlund, M., Palfreyman, M. T., Watanabe, S., Olsen, S. & Jorgensen, E. M. Open syntaxin docks synaptic vesicles. PLoS Biol. 5, 1695–1711 (2007).
Richmond, J. E., Weimer, R. M. & Jorgensen, E. M. An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming. Nature 412, 338–341 (2001).
pubmed: 11460165
pmcid: 2585764
Watanabe, S. et al. Ultrafast endocytosis at mouse hippocampal synapses. Nature 504, 242–247 (2013).
pubmed: 24305055
pmcid: 3957339
Watanabe, S. et al. Ultrafast endocytosis at Caenorhabditis elegans neuromuscular junctions. eLife 2013, e00723 (2013).
Chang, S., Trimbuch, T. & Rosenmund, C. Synaptotagmin-1 drives synchronous Ca
pubmed: 29230057
Ritzau-jost, A. et al. Ultrafast action potentials mediate kilohertz signaling at a central synapse. Neuron 84, 152–163 (2014).
pubmed: 25220814
Pyott, S. J. & Rosenmund, C. The effects of temperature on vesicular supply and release in autaptic cultures of rat and mouse hippocampal neurons. J. Physiol. 539, 523–535 (2002).
pubmed: 11882684
pmcid: 2290147
Miki, T. et al. Actin- and myosin-dependent vesicle loading of presynaptic docking sites prior to exocytosis. Neuron 91, 808–823 (2016).
pubmed: 27537485
Miki, T., Nakamura, Y., Malagon, G., Neher, E. & Marty, A. Two-component latency distributions indicate two-step vesicular release at simple glutamatergic synapses. Nat. Commun. 9, 3943 (2018).
pubmed: 30258069
pmcid: 6158186
Neher, E. & Brose, N. Dynamically primed synaptic vesicle states: key to understand synaptic short-term plasticity. Neuron 100, 1283–1291 (2018).
pubmed: 30571941
Betz, W. J. & Bewick, G. S. Optical analysis of synaptic vesicle recycling at the frog neuromuscular junction. Science 255, 200–203 (1992).
pubmed: 1553547
Dutta, D., Williamson, C. D., Cole, N. B. & Donaldson, J. G. Pitstop 2 is a potent inhibitor of clathrin-independent endocytosis. PLoS ONE 7, e45799 (2012).
pubmed: 23029248
pmcid: 3448704
Von Kleist, L. et al. Role of the clathrin terminal domain in regulating coated pit dynamics revealed by small molecule inhibition. Cell 146, 471–484 (2011).
Watanabe, S. et al. Clathrin regenerates synaptic vesicles from endosomes. Nature 515, 228–233 (2014).
pubmed: 25296249
pmcid: 4291189
Jones, H. C. & Keep, R. F. Brain fluid calcium concentration and response to acute hypercalcaemia during development in the rat. J. Physiol. 402, 579–593 (1988).
pubmed: 3236250
pmcid: 1191910
Hoppa, M. B., Gouzer, G., Armbruster, M. & Ryan, T. A. Control and plasticity of the presynaptic action potential waveform at small CNS nerve terminals. Neuron 84, 778–789 (2014).
pubmed: 25447742
pmcid: 4283217
Rudolph, S., Tsai, M.-C., von Gersdorff, H. & Wadiche, J. I. The ubiquitous nature of multivesicular release. Trends Neurosci. 38, 428–438 (2015).
pubmed: 26100141
pmcid: 4495900
Sakamoto, H. et al. Synaptic weight set by Munc13-1 supramolecular assemblies. Nat. Neurosci. 21, 41–55 (2018).
pubmed: 29230050
Tang, A.-H. et al. A trans-synaptic nanocolumn aligns neurotransmitter release to receptors. Nature 536, 210–214 (2016).
pubmed: 27462810
pmcid: 5002394
Hruska, M., Henderson, N., Le Marchand, S. J., Jafri, H. & Dalva, M. B. Synaptic nanomodules underlie the organization and plasticity of spine synapses. Nat. Neurosci. 21, 671–682 (2018).
pubmed: 29686261
pmcid: 5920789
Dobrunz, L. E., Huang, E. P. & Stevens, C. F. Very short-term plasticity in hippocampal synapses. Proc. Natl Acad. Sci. USA 94, 14843–14847 (1997).
pubmed: 9405701
Holderith, N. et al. Release probability of hippocampal glutamatergic terminals scales with the size of the active zone. Nat. Neurosci. 15, 988–997 (2012).
pubmed: 22683683
pmcid: 3386897
Kaeser, P. S. & Regehr, W. G. Molecular mechanisms for synchronous, asynchronous, and spontaneous neurotransmitter release. Annu. Rev. Physiol. 76, 333–363 (2014).
pubmed: 24274737
Grauel, M. K. et al. RIM-binding protein 2 regulates release probability by fine-tuning calcium channel localization at murine hippocampal synapses. Proc. Natl Acad. Sci. USA 113, 11615–11620 (2016).
pubmed: 27671655
Adler, E., Augustine, J., Duffy, N. & Charlton, P. Alien intracellular calcium chelators attenuate release at the squid giant synapse. J. Neurosci. 11, 1496–1507 (1991).
pubmed: 1675264
pmcid: 6575403
Chen, C. & Regehr, W. G. Contributions of residual calcium to fast synaptic transmission. J. Neurosci. 19, 6257–6266 (1999).
pubmed: 10414955
pmcid: 6782810
Dittman, J. S. & Regehr, W. G. Calcium dependence and recovery kinetics of presynaptic depression at the climbing fiber to Purkinje cell synapse. J. Neurosci. 18, 6147–6162 (1998).
pubmed: 9698309
pmcid: 6793194
Sakaba, T. & Neher, E. Calmodulin mediates rapid recruitment of fast-releasing synaptic vesicles at a calyx-type synapse. Neuron 32, 1119–1131 (2001).
pubmed: 11754842
Redman, S. Quantal analysis of synaptic potentials in neurons of the central nervous system. Physiol. Rev. 70, 165–198 (1990).
pubmed: 2404288
Tong, G. & Jahr, C. E. Multivesicular release from excitatory synapses of cultured hippocampal neurons. Neuron 12, 51–59 (1994).
pubmed: 7507341
Auger, C., Kondo, S. & Marty, A. Multivesicular release at single functional synaptic sites in cerebellar stellate and basket cells. J. Neurosci. 18, 4532–4547 (1998).
pubmed: 9614230
pmcid: 6792676
Balaji, J. & Ryan, T. A. Single-vesicle imaging reveals that synaptic vesicle exocytosis and endocytosis are coupled by a single stochastic mode. Proc. Natl Acad. Sci. USA 104, 20576–20581 (2007).
pubmed: 18077369
Abenavoli, A. et al. Multimodal quantal release at individual hippocampal synapses: evidence for no lateral inhibition. J. Neurosci. 22, 6336–6346 (2002).
pubmed: 12151511
pmcid: 6758134
Nakamura, Y. et al. Nanoscale distribution of presynaptic Ca
pubmed: 25533484
pmcid: 4305191
Rebola, N. et al. Distinct nanoscale calcium channel and synaptic vesicle topographies contribute to the diversity of synaptic function. Neuron 104, 693–710.e9 (2019).
pubmed: 31558350
Sabatini, B. L. & Regehr, W. G. Optical measurement of presynaptic calcium currents. Biophys. J. 74, 1549–1563 (1998).
pubmed: 9512051
pmcid: 1299501
Raingo, J. et al. VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission. Nat. Neurosci. 15, 738–745 (2012).
pubmed: 22406549
pmcid: 3337975
Turecek, J. & Regehr, X. W. G. Synaptotagmin 7 mediates both facilitation and asynchronous release at granule cell synapses. J. Neurosci. 38, 3240–3251 (2018).
pubmed: 29593071
pmcid: 5884459
Weber, J. P., Toft-Bertelsen, T. L., Mohrmann, R., Delgado-Martinez, I. & Sørensen, J. B. Synaptotagmin-7 is an asynchronous calcium sensor for synaptic transmission in neurons expressing SNAP-23. PLoS ONE 9, e114033 (2014).
pubmed: 25422940
pmcid: 4244210
Yao, J., Gaffaney, J. D., Kwon, S. E. & Chapman, E. R. Doc2 is a Ca
pubmed: 22036572
pmcid: 3220409
Hu, Z., Tong, X. J. & Kaplan, J. M. UNC-13L, UNC-13S, and Tomosyn form a protein code for fast and slow neurotransmitter release in Caenorhabditis elegans. eLife 2013, e00967 (2013).
Böhme, M. A. et al. Active zone scaffolds differentially accumulate Unc13 isoforms to tune Ca
pubmed: 27526206
Clustering, C. C. et al. Bruchpilot promotes active zone assembly, Ca
Lipstein, N. et al. Dynamic control of synaptic vesicle replenishment and short-term plasticity by Ca
pubmed: 23770256
Jackman, S. L., Turecek, J., Belinsky, J. E. & Regehr, W. G. The calcium sensor synaptotagmin 7 is required for synaptic facilitation. Nature 529, 88–91 (2016).
pubmed: 26738595
pmcid: 4729191
Jackman, S. L. & Regehr, W. G. The mechanisms and functions of synaptic facilitation. Neuron 94, 447–464 (2017).
pubmed: 28472650
pmcid: 5865607
Kaech, S. & Banker, G. Culturing hippocampal neurons. Nat. Protoc. 1, 2406–2415 (2006).
pubmed: 17406484
Hoopmann, P., Rizzoli, S. O. & Betz, W. J. Imaging synaptic vesicle recycling by staining and destaining vesicles with FM dyes. Cold Spring Harb. Protoc. 7, 77–83 (2012).
Allen, C. & Stevens, C. F. An evaluation of causes for unreliability of synaptic transmission. Proc. Natl Acad. Sci. USA 91, 10380–10383 (1994).
pubmed: 7937958
Rosenmund, C., Clements, J. D. & Westbrook, G. L. Nonuniform probability of glutamate release at a hippocampal synapse. Science 262, 754–757 (1993).
pubmed: 7901909
Hessler, N. A., Shirke, A. M. & Malinow, R. The probability of transmitter release at a mammalian central synapse. Nature 366, 569–572 (1993).
pubmed: 7902955
Jensen, T. P. et al. Multiplex imaging relates quantal glutamate release to presynaptic Ca
pubmed: 30926781
pmcid: 6441074
Watanabe, S. Flash-and-freeze: coordinating optogenetic stimulation with rapid freezing to visualize membrane dynamics at synapses with millisecond resolution. Front. Synaptic Neurosci. 8, 24 (2016).
pubmed: 27594835
pmcid: 4990539