Abstract
Traditional models of synaptic transmission hold that release sites within an active zone operate independently. Although the release of multiple vesicles (multivesicular release; MVR) from single active zones occurs at some central synapses, MVR is not thought to require coordination among release sites. Ribbon synapses seem to be optimized to release many vesicles over an extended period, but the dynamics of MVR at ribbon synapses is unknown. We examined MVR at a ribbon synapse in a retinal slice preparation using paired recordings from presynaptic rod bipolar and postsynaptic AII amacrine cells. When evoked release was highly desynchronized, discrete postsynaptic events were larger than quantal miniature excitatory postsynaptic currents (mEPSCs) but had the same time course. The amplitude of these multiquantal mEPSCs, which seem to arise from the essentially simultaneous release of multiple vesicles, was reduced by lowering release probability. The release synchrony reflected in these multivesicular events suggests that release within an active zone is coordinated during MVR.
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References
Propst, J.W. & Ko, C.P. Correlations between active zone ultrastructure and synaptic function studied with freeze-fracture of physiologically identified neuromuscular junctions. J. Neurosci. 7, 3654–3664 (1987).
Katz, B. The Release of Neural Transmitter Substances (Liverpool University Press, Liverpool, UK, 1969).
Redman, S. Quantal analysis of synaptic potentials in neurons of the central nervous system. Physiol. Rev. 70, 165–198 (1990).
Korn, H. & Faber, D.S. Quantal analysis and synaptic efficacy in the CNS. Trends Neurosci. 14, 439–445 (1991).
Stevens, C.F. & Wang, Y. Facilitation and depression at single central synapses. Neuron 14, 795–802 (1995).
Silver, R.A., Momiyama, A. & Cull-Candy, S.G. Locus of frequency-dependent depression identified with multiple-probability fluctuation analysis at rat climbing fibre-Purkinje cell synapses. J. Physiol. 510, 881–902 (1998).
Tong, G. & Jahr, C.E. Multivesicular release from excitatory synapses of cultured hippocampal neurons. Neuron 12, 51–59 (1994).
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).
Wadiche, J.I. & Jahr, C.E. Multivesicular release at climbing fiber-Purkinje cell synapses. Neuron 32, 301–313 (2001).
Oertner, T.G., Sabatini, B.L., Nimchinsky, E.A. & Svoboda, K. Facilitation at single synapses probed with optical quantal analysis. Nat. Neurosci. 5, 657–664 (2002).
Silver, R.A., Lubke, J., Sakmann, B. & Feldmeyer, D. High-probability uniquantal transmission at excitatory synapses in barrel cortex. Science 302, 1981–1984 (2003).
von Gersdorff, H., Vardi, E., Matthews, G. & Sterling, P. Evidence that vesicles on the synaptic ribbon of retinal bipolar neurons can be rapidly released. Neuron 16, 1221–1227 (1996).
Heidelberger, R., Heinemann, C., Neher, E. & Matthews, G. Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 371, 513–515 (1994).
von Gersdorff, H. & Matthews, G. Depletion and replenishment of vesicle pools at a ribbon-type synaptic terminal. J. Neurosci. 17, 1919–1927 (1997).
Parsons, T.D. & Sterling, P. Synaptic ribbon: conveyor belt or safety belt. Neuron 37, 379–382 (2003).
Strettoi, E., Dacheux, R.F. & Raviola, E. Synaptic connections of rod bipolar cells in the inner plexiform layer of the rabbit retina. J. Comp. Neurol. 295, 449–466 (1990).
Chun, M.H., Han, S.H., Chung, J.W. & Wassle, H. Electron microscopic analysis of the rod pathway of the rat retina. J. Comp. Neurol. 332, 421–432 (1993).
Tong, G. & Jahr, C.E. Block of glutamate transporters potentiates postsynaptic excitation. Neuron 13, 1195–1203 (1994).
Singer, J.H. & Diamond, J.S. Sustained Ca2+ entry elicits transient postsynaptic currents at a retinal ribbon synapse. J. Neurosci. 23, 10923–10933 (2003).
Cui, J., Ma, Y.P., Lipton, S.A. & Pan, Z.H. Glycine receptors and glycinergic synaptic input at the axon terminals of mammalian retinal rod bipolar cells. J. Physiol. 553, 895–909 (2003).
Hartveit, E. Reciprocal synaptic interactions between rod bipolar cells and amacrine cells in the rat retina. J. Neurophysiol. 81, 2923–2936 (1999).
Koulen, P. et al. Presynaptic and postsynaptic localization of GABAB receptors in neurons of the rat retina. Eur. J. Neurosci. 10, 1446–1456 (1998).
Diamond, J.S. & Jahr, C.E. Transporters buffer synaptically released glutamate on a submillisecond time scale. J. Neurosci. 17, 4672–4687 (1997).
Muresan, V., Lyass, A. & Schnapp, B.J. The kinesin motor KIF3A is a component of the presynaptic ribbon in vertebrate photoreceptors. J. Neurosci. 19, 1027–1037 (1999).
Young, H.M. & Vaney, D.I. Rod-signal interneurons in the rabbit retina: 1. rod bipolar cells. J. Comp. Neurol. 310, 139–153 (1991).
Li, W., Trexler, E.B. & Massey, S.C. Glutamate receptors at rod bipolar ribbon synapses in the rabbit retina. J. Comp. Neurol. 448, 230–248 (2002).
Strettoi, E., Raviola, E. & Dacheux, R.F. Synaptic connections of the narrow-field, bistratified rod amacrine cell (AII) in the rabbit retina. J. Comp. Neurol. 325, 152–168 (1992).
Vaney, D.I., Gynther, I.C. & Young, H.M. Rod-signal interneurons in the rabbit retina: 2. AII amacrine cells. J. Comp. Neurol. 310, 154–169 (1991).
Sterling, P., Freed, M.A. & Smith, R.G. Architecture of rod and cone circuits to the on-beta ganglion cell. J. Neurosci. 8, 623–642 (1988).
del Castillo, J. & Katz, B. Quantal components of the end-plate potential. J. Physiol. 124, 157–181 (1954).
Van der Kloot, W. Estimating the timing of quantal releases during end-plate currents at the frog neuromuscular junction. J. Physiol. 402, 595–603 (1988).
Diamond, J.S. & Jahr, C.E. Asynchronous release of synaptic vesicles determines the time course of the AMPA receptor-mediated EPSC. Neuron 15, 1097–1107 (1995).
Isaacson, J.S. & Walmsley, B. Counting quanta: direct measurements of transmitter release at a central synapse. Neuron 15, 875–884 (1995).
Lagnado, L., Gomis, A. & Job, C. Continuous vesicle cycling in the synaptic terminal of retinal bipolar cells. Neuron 17, 957–967 (1996).
Frerking, M., Borges, S. & Wilson, M. Variation in GABA mini amplitude is the consequence of variation in transmitter concentration. Neuron 15, 885–895 (1995).
Slaughter, M.M. & Miller, R.F. 2-amino-4-phosphonobutyric acid: a new pharmacological tool for retina research. Science 211, 182–185 (1981).
Otsu, Y. et al. Competition between phasic and asynchronous release for recovered synaptic vesicles at developing hippocampal autaptic synapses. J. Neurosci. 24, 420–433 (2004).
Euler, T. & Masland, R.H. Light-evoked responses of bipolar cells in a mammalian retina. J. Neurophysiol. 83, 1817–1829 (2000).
Matsui, K. & Jahr, C.E. Ectopic release of synaptic vesicles. Neuron 40, 1173–1183 (2003).
Zenisek, D., Steyer, J.A. & Almers, W. Transport, capture and exocytosis of single synaptic vesicles at active zones. Nature 406, 849–854 (2000).
Alvarez deToledo, G. & Fernandez, J.M. Compound versus multigranular exocytosis in peritoneal mast cells. J. Gen. Physiol. 95, 397–409 (1990).
Hansen, N.J., Antonin, W. & Edwardson, J.M. Identification of SNAREs involved in regulated exocytosis in the pancreatic acinar cell. J. Biol. Chem. 274, 22871–22876 (1999).
Alvarez deToledo, G., Fernandez-Chacon, R. & Fernandez, J.M. Release of secretory products during transient vesicle fusion. Nature 363, 554–558 (1993).
Barlow, H.B., Levick, W.R. & Yoon, M. Responses to single quanta of light in retinal ganglion cells of the cat. Vision Res. 3 (Suppl.), 87–101 (1971).
Sakitt, B. Counting every quantum. J. Physiol. 223, 131–150 (1972).
Nelson, R. AII amacrine cells quicken time course of rod signals in the cat retina. J. Neurophysiol. 47, 928–947 (1982).
Field, G.D. & Rieke, F. Nonlinear signal transfer from mouse rods to bipolar cells and implications for visual sensitivity. Neuron 34, 773–785 (2002).
Acknowledgements
We thank D. Faber, S. Massey, P. Sterling and L.-G. Wu for helpful discussions. This work was supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program, a National Institute of Neurological Disorders and Stroke Career Development Award to J.H.S., EY11105 (to N.V.) and EY00828 (to P. Sterling, supporting L.L.).
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Singer, J., Lassová, L., Vardi, N. et al. Coordinated multivesicular release at a mammalian ribbon synapse. Nat Neurosci 7, 826–833 (2004). https://doi.org/10.1038/nn1280
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DOI: https://doi.org/10.1038/nn1280
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