The probability of transmitter release at a mammalian central synapse

WHEN an action potential reaches a synaptic terminal, fusion of a transmitter-containing vesicle with the presynaptic membrane occurs with a probability (pr) of less than one1. Despite the fundamental importance of this parameter, pr has not been directly measured in the central nervous system. Here we describe a novel approach to determine pr monitoring the decrement of NMDA (N-methyl-D-aspartate)-receptor mediated synaptic currents in the presence of the use-dependent channel blocker MK-801 (ref. 2). On a single postsynaptic CA1 hippocampal slice neuron, two classes of synapses with a sixfold difference in pr are resolved. Synapses with low pr contribute to over half of transmission and are more sensitive to drugs enhancing transmitter release. Switching between these two classes of synapses provides the potential for large changes in synaptic efficacy and could underlie forms of activity-dependent plasticity.

[1]  H. Atwood.  Variation in Physiological Properties of Crustacean Motor Synapses , 1967, Nature.

[2]  R Rahamimoff,et al.  A dual effect of calcium ions on neuromuscular facilitation , 1968, The Journal of physiology.

[3]  B. Katz.  The release of neural transmitter substances , 1969 .

[4]  G. Strichartz,et al.  The Inhibition of Sodium Currents in Myelinated Nerve by Quaternary Derivatives of Lidocaine , 1973, The Journal of general physiology.

[5]  J. Jack,et al.  Modifications to synaptic transmission at group Ia synapses on cat spinal motoneurones by 4‐aminopyridine. , 1981, The Journal of physiology.

[6]  B. Walmsley,et al.  Amplitude fluctuations in synaptic potentials evoked in cat spinal motoneurones at identified group Ia synapses. , 1983, The Journal of physiology.

[7]  D. Faber,et al.  Synaptic transmission mediated by single club endings on the goldfish Mauthner cell. II. Plasticity of excitatory postsynaptic potentials , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  B. Bean,et al.  Block of N-methyl-D-aspartate-activated current by the anticonvulsant MK-801: selective binding to open channels. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[9]  B. Walmsley,et al.  Nonuniform release probabilities underlie quantal synaptic transmission at a mammalian excitatory central synapse. , 1988, Journal of neurophysiology.

[10]  H. Clamann,et al.  Variance analysis of excitatory postsynaptic potentials in cat spinal motoneurons during posttetanic potentiation. , 1989, Journal of neurophysiology.

[11]  R. Nicoll,et al.  Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices , 1990, Neuron.

[12]  G. Westbrook,et al.  Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents , 1990, Nature.

[13]  J. D. Clements,et al.  Activation kinetics reveal the number of glutamate and glycine binding sites on the N-methyl-d-aspartate receptor , 1991, Neuron.

[14]  D. Colquhoun,et al.  Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration , 1992, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[15]  R. Malinow,et al.  Direct measurement of quantal changes underlying long-term potentiation in CA1 hippocampus , 1992, Neuron.

[16]  CE Jahr,et al.  NMDA channel behavior depends on agonist affinity , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  G. Westbrook,et al.  The time course of glutamate in the synaptic cleft. , 1992, Science.

[18]  C. Jahr,et al.  High probability opening of NMDA receptor channels by L-glutamate. , 1992, Science.

[19]  Christian Rosenmund,et al.  Nonuniform probability of glutamate release at a hippocampal synapse. , 1993, Science.