Saturation of postsynaptic glutamate receptors after quantal release of transmitter

Miniature excitatory postsynaptic currents (mEPSCs) were elicited from small numbers of release sites after brief microperfusion of Ba2+ and K+ onto proximal dendritic processes of hippocampal neurons in culture. Temporal summation of closely timed mEPSCs deviated significantly from linearity. The number of instances of closely timed mEPSCs that were also closely matched in terms of peak amplitudes was significantly greater than that expected by chance. Amplitude pairing became statistically more significant after prolongation of mEPSC duration and inhibition of glutamate receptor desensitization with cyclothiazide. These results are best explained by postsynaptic receptors that approach saturation after quantal release of transmitter.

[1]  L. Trussell,et al.  Desensitization of AMPA receptors upon multiquantal neurotransmitter release , 1993, Neuron.

[2]  C. Stevens,et al.  Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B Sakmann,et al.  Quantal analysis of inhibitory synaptic transmission in the dentate gyrus of rat hippocampal slices: a patch‐clamp study. , 1990, The Journal of physiology.

[4]  L. Vyklický,et al.  Hippocampal neurons exhibit cyclothiazide-sensitive rapidly desensitizing responses to kainate , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  Peter Somogyi,et al.  Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites , 1994, Nature.

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

[7]  J. E. Huettner.  Glutamate receptor channels in rat DRG neurons: Activation by kainate and quisqualate and blockade of desensitization by con A , 1990, Neuron.

[8]  M. Blaustein,et al.  Strontium, barium, and manganese metabolism in isolated presynaptic nerve terminals. , 1987, The American journal of physiology.

[9]  KM Harris,et al.  Dendritic spines of CA 1 pyramidal cells in the rat hippocampus: serial electron microscopy with reference to their biophysical characteristics , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[11]  K. Harris,et al.  Localization of synapses in rat cortical cultures , 1993, Neuroscience.

[12]  Kristen M. Harris,et al.  Quantal analysis and synaptic anatomy — integrating two views of hippocampal plasticity , 1993, Trends in Neurosciences.

[13]  Y. Yaari,et al.  Delayed release of transmitter at the frog neuromuscular junction , 1973, The Journal of physiology.

[14]  K. Stratford,et al.  Quantal analysis of excitatory synaptic action and depression in hippocampal slices , 1991, Nature.

[15]  S. Redman.  Quantal analysis of synaptic potentials in neurons of the central nervous system. , 1990, Physiological reviews.

[16]  G. Lynch,et al.  Modulation of the time course of fast EPSCs and glutamate channel kinetics by aniracetam. , 1991, Science.

[17]  P. Usherwood.  Transmitter release from insect excitatory motor nerve terminals , 1972, The Journal of physiology.

[18]  Kahori Yamada,et al.  Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  C F Stevens,et al.  Inferences about membrane properties from electrical noise measurements. , 1972, Biophysical journal.

[20]  B. Sakmann,et al.  Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus. , 1993, The Journal of physiology.

[21]  Shaul Hestrin,et al.  Different glutamate receptor channels mediate fast excitatory synaptic currents in inhibitory and excitatory cortical neurons , 1993, Neuron.

[22]  R. Nicoll,et al.  Long-term potentiation is associated with increases in quantal content and quantal amplitude , 1992, Nature.

[23]  KM Harris,et al.  Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation [published erratum appears in J Neurosci 1992 Aug;12(8):following table of contents] , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  Gang Tong,et al.  Multivesicular release from excitatory synapses of cultured hippocampal neurons , 1994, Neuron.

[25]  H. Kita,et al.  The intervals between miniature end‐plate potentials in the frog are unlikely to be independently or exponentially distributed , 1974, The Journal of physiology.

[26]  E. M. Silinsky.  On the role of barium in supporting the asynchronous release of acetylcholine quanta by motor nerve impulses. , 1978, The Journal of physiology.

[27]  R. Tsien,et al.  Distinctive pharmacology and kinetics of cloned neuronal Ca2+ channels and their possible counterparts in mammalian CNS neurons , 1993, Neuropharmacology.

[28]  J. Clements.  Quantal synaptic transmission? , 1991, Nature.

[29]  P. Andersen,et al.  Putative Single Quantum and Single Fibre Excitatory Postsynaptic Currents Show Similar Amplitude Range and Variability in Rat Hippocampal Slices , 1992, The European journal of neuroscience.

[30]  C. Stevens,et al.  NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus , 1989, Nature.

[31]  F. Edwards.  LTP is a long term problem , 1991, Nature.

[32]  C. Stevens.  Quantal release of neurotransmitter and long-term potentiation , 1993, Cell.

[33]  Steven Mennerick,et al.  Glial contributions to excitatory neurotransmission in cultured hippocampal cells , 1994, Nature.