Abstract
In many studies of central synaptic transmission, the quantal properties of miniature synaptic events do not match those derived from synaptic events evoked by action potentials. Here we show that at mossy fiber–granule cell (MF–gc) synapses of mature cerebellum, evoked excitatory postsynaptic currents (EPSCs) are multiquantal, and their amplitudes vary in discrete steps, whereas miniature (m)EPSCs are monoquantal or multiquantal with quantal parameters identical to those of the EPSCs. In contrast, at immature MF–gc synapses, EPSCs are multiquantal, but their amplitudes do not vary in discrete steps, whereas most mEPSCs seem to be monoquantal with a broad and skewed amplitude distribution. The results demonstrate that quantal variance decreases during synaptic development. They also directly confirm the quantal hypothesis of neurotransmission at a mature brain synapse.
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References
Peters, A., Palay, S. L. & Webster, H. D. The Fine Structure Of The Nervous System. Neurons And Their Supporting Cells. (Oxford Univ. Press, New York, 1991).
Fatt, P. & Katz, B. Spontaneous subthreshold activity at motor nerve endings. J. Physiol. (Lond.) 117, 109–128 (1952).
del Castillo, J. & Katz, B. Quantal components of the endplate potential. J. Physiol. (Lond.) 124, 560–573 (1954).
Katz, B. Nerve, Muscle and Synapse. (McGraw-Hill, New York, 1966).
Blackman, J. G., Ginsborg, B. L. & Ray, C. Spontaneous synaptic activity in sympathetic ganglion cells of the frog. J. Physiol. (Lond.) 167, 389–401 (1963).
Martin, A. R. & Pilar, G. Quantal components of the synaptic potential in the ciliary ganglion of the chick. J. Physiol. (Lond.) 175, 1–16 ( 1964).
Dennis, M. J., Harris, A. J. & Kuffler, S. W. Synaptic transmission and its duplication by focally applied acetylcholine in parasympathetic neurons in the heart of the frog. Proc. R. Soc. Lond. B Biol. Sci. 177, 509 –539 (1971).
Bornstein, J. C. Spontaneous multiquantal release at synapses in guinea-pig hypogastric ganglia: evidence that release can occur in bursts. J. Physiol. (Lond.) 282, 375–398 ( 1978).
Bekkers, J. M. Quantal analysis of synaptic transmission in the central nervous system. Curr. Opin. Neurobiol. 4, 360–365 (1994).
Bennett, M. R. The origin of Gaussian distributions of synaptic potentials. Prog. Neurobiol. 46, 331–350 ( 1995).
Edwards, F. A., Konnerth, A. & Sakmann, B. Quantal analysis of inhibitory synaptic transmission in the dentate gyrus of rat hippocampal slices: a patch clamp study. J. Physiol. (Lond.) 430, 213–249 (1990).
Larkman, A., Stratford, K. & Jack, J. Quantal analysis of excitatory synaptic action and depression in hippocampal slices. Nature 350, 344– 347 (1991).
Paulsen, O. & Heggelund, P. The quantal size at retinogeniculate synapses determined from spontaneous and evoked EPSCs in guinea-pig thalamic slices. J. Physiol. (Lond.) 480, 505– 511 (1994).
Paulsen O. & Heggelund, P. Quantal properties of spontaneous EPSCs in neurones of the guinea-pig dorsal lateral geniculate nucleus. J. Physiol. (Lond.) 496, 759–772 (1996).
Min, M.-Y. & Appenteng, K. Multimodal distributions of amplitudes of miniature and spontaneous EPSPs recorded in rat trigeminal motoneurones. J. Physiol. (Lond.) 494, 171– 182 (1996).
Jonas, P., Major, G. & Sakmann, B. Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. J. Physiol. (Lond.) 472, 615–663 ( 1993).
Kraszewski, K. & Grantyn, R. Unitary, quantal and miniature GABA-activated synaptic chloride currents in cultured neurons from the rat superior colliculus. Neuroscience 47, 555–570 (1992).
Liu, G. & Feldman, J. L. Quantal synaptic transmission in phrenic motor nucleus. J. Neurophysiol. 68, 1468–1471 (1992).
Kullmann, D. M. & Nicholl, R. A. Long-term potentiation is associated with increases in quantal content and quantal amplitude. Nature 357, 240–244 ( 1992).
Liao, D., Jones, A. & Malinow, R. Direct measurement of quantal changes underlying long-term potentiation in CA1 hippocampus. Neuron 9, 1089–1097 (1992).
Silver, R. A., Cull-Candy, S. G. & Takahashi, T. Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites. J. Physiol. (Lond.) 494, 231–251 (1996).
Bekkers, J. M. & Stevens, C. F. Quantal analysis of EPSCs recorded from small numbers of synapses in hippocampal cultures. J. Neurophysiol. 73, 1145– 1156 (1995).
Silver, R. A., Traynelis, S. F. & Cull-Candy, S. G. Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses in situ. Nature 355 , 163–166 (1992).
Ropert, N., Miles, R. & Korn, H. Characteristics of miniature inhibitory postsynaptic currents in CA1 pyramidal neurones of rat hippocampus. J. Physiol. (Lond.) 428 , 707–722 (1990).
Korn, H., Bausela, F., Charpier, S. & Faber, D. S. Synaptic noise and multiquantal release at dendritic synapses. J. Neurophysiol. 70, 1249–1254 (1993).
Ulrich, D. & Luscher, H.-R. Miniature excitatory synaptic currents corrected for dendritic cable properties reveal quantal size and variance. J. Neurophysiol. 69, 1769– 1773 (1993).
Hámori, J. & Somogyi, J. Differentiation of cerebellar mossy fiber synapses in the rat: A quantitative electron microscope study. J. Comp. Neurol. 220, 365– 377 (1983).
Mason, C. M. & Gregory, E. Postnatal maturation of cerebellar mossy and climbing fibers; transient expression of dual features on single axons. J. Neurosci. 7, 1715– 1735 (1984).
Traynelis, S. F., Silver, R. A. & Cull-Candy, S. G. Estimated conductance of glutamate receptor channels activated during EPSCs at the cerebellar mossy fiber-granule cell synapse. Neuron 11, 279–289 (1993).
D'Angelo, E., De Filippi, G., Rossi, P. & Taglietti, V. Synaptic excitation of individual rat cerebellar granule cells in situ : evidence for the role of NMDA receptors. J. Physiol. (Lond.) 484, 397–413 ( 1995).
Jack, J. B., Larkman, A. U., Major, G. & Stratford, K. J. in Molecular and Cellular Mechanisms of Neurotransmitter Release (eds Stjarne, L. et al. ) 275–299 (Raven, New York, 1994).
Fox, C. A., Hillman, D. E., Siegesmund, K. A. & Dutta, C. R. The primate cerebellar cortex: A Golgi and electron microscopic study. Prog. Brain. Res. 25, 172–225 (1967).
Jakab, R L. & Hámori, J. Quantitative morphology and synaptology of cerebellar glomeruli in the rat. Anat. Embryol. 179, 81–88 ( 1988).
Katz, B. & Miledi, R. The measurement of synaptic delay and the timecourse of acetylcholine release at the neuromuscular junction. Proc. R. Soc. Lond. B Biol. Sci. 161, 483 –495 (1965).
Barrett, E. F. & Stevens, C. F. Quantal independence and uniformity of presynaptic release kinetics at the frog neuromuscular junction. J. Physiol. (Lond.) 277, 665– 689 (1972).
Walmsley, B. Interpretation of quantal peaks in distributions of evoked synaptic transmission at central synapses. Proc. R. Soc. Lond. B Biol. Sci. 261, 245–250 (1995).
Meiri, U. & Rahamimoff, R. Activation of transmitter release by strontium and calcium ions at the neuromuscular junction. J. Physiol. (Lond.) 215, 709–726 (1971).
Abdul-Ghani, M. A., Valiante, T. A. & Pennefather, P. S. Sr 2+ and quantal events at excitatory synapses between mouse hippocampal neurons in culture. J. Physiol. (Lond.) 495, 112–125. (1996).
Dilger, J. P., Brett, R. S., Poppers, D. M. & Liu, Y. The temperature dependence of some kinetic and conductance properties of acetylcholine receptor channels . Biochim. Biophys. Acta 1063, 253–258 (1991).
Feldmeyer, D. & Cull-Candy, S. G. Temperature dependence of NMDA receptor channel conductance levels in outside-out patches from isolated cerebellar granule cells of the rat. J. Physiol. (Lond.) 459, 284P (1993).
Cohen, I. S. & Van Der Kloot, W. Effects of low temperature and terminal membrane potential on quantal size at frog neuromuscular junction. J. Physiol. (Lond.) 336, 335– 344 (1983).
Van Der Kloot, W. & Cohen, I. S. Temperature effects on spontaneous and evoked quantal size at the frog neuromuscular junction. J. Neurosci. 9, 2200–2203 (1984).
Liu, G. & Tsien, R. W. Properties of synaptic transmission at single hippocampal synaptic boutons. Nature 375, 404–408 (1995).
von Kitzing, E., Jonas, P. & Sakmann B. in Molecular and Cellular Mechanisms of Neurotransmitter Release (eds Stjarne, L. et al. ) 235– 260 (Raven, New York, 1994).
Palay, S. L. & Chan-Palay, V. in Cerebellar Cortex: Cytology and Organization 142–179 (Springer, Berlin, 1974).
Edwards, F. Anatomy and electrophysiology of fast central synapses lead to a structural model for long term potentiation. Physiol. Rev. 75, 759–787 (1995).
Clements, J. D. Transmitter timecourse in the synaptic cleft: its role in central synaptic function. Trends Neurosci. 19, 163– 171 (1996).
Brickley, S. G., Cull-Candy, S. G. & Farrant, M. Development of a tonic form of synaptic inhibition in rat cerebellar granule cells resulting from persistent activation of GABA A receptors. J. Physiol. (Lond.) 497, 753–759 (1996).
Tia, S., Weng, J. F., Kotchabhakdi, N. & Vicini, S. Developmental changes of inhibitory synaptic currents in cerebellar granule neurons: role of GABAA receptor α6 subunit. J. Neurosci. 16, 3630–3640 (1996).
Wall, M. J. & Usowicz, M. M. Development of action potential-dependent and independent spontaneous GABAA receptor-mediated currents in granule cells of postnatal rat cerebellum. Eur. J. Neurosci. 9, 533–548 (1997).
Acknowledgements
This work was supported by The Wellcome Trust. We are grateful for comments on on an earlier version of the manuscript from Hywel Bufton, Graeme Henderson, John Isaac, Neil Marrion and Elizabeth Tringham. We thank John Isaac for suggesting the paired-pulse experiments and Hywel Bufton for recording some of the EPSCs and mEPSCs in young animals.
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Wall, M., Usowicz, M. Development of the quantal properties of evoked and spontaneous synaptic currents at a brain synapse. Nat Neurosci 1, 675–682 (1998). https://doi.org/10.1038/3677
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DOI: https://doi.org/10.1038/3677
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