Ultrastructural Correlates of Quantal Synaptic Function at Single CNS Synapses

We have tested the hypothesis that functional differences between synapses are associated with ultrastructure in cultured cortical neurons. Using Ca(2+) imaging, we measured NMDA receptor-mediated miniature synaptic calcium transients attributed to the spontaneous release of single transmitter quanta. After imaging, the identified neurons were processed for serial transmission electron microscopy. At sites of quantal NMDA receptor-dependent Ca(2+) transients, we confirmed the presence of excitatory synapses and measured spine size and synaptic contact area. Our results demonstrate that synapse size correlates positively with the amplitude of the NMDA receptor-mediated postsynaptic response, suggesting that larger synapses express a greater number of NMDA receptors. Therefore, regulation of quantal amplitude may involve processes that alter synapse size.

[1]  W. Greenough,et al.  Subsynaptic plate perforations: changes with age and experience in the rat. , 1978, Science.

[2]  S. Young,et al.  Effect of anisomycin on stimulation-induced changes in dendritic spines of the dentate granule cells , 1982, Journal of neurocytology.

[3]  K. Harris,et al.  Membrane structure at synaptic junctions in area CA1 of the rat hippocampus , 1986, Neuroscience.

[4]  W. Levy,et al.  Synaptic interface surface area increases with long-term potentiation in the hippocampal dentate gyrus , 1988, Brain Research.

[5]  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.

[6]  R. K. S. Calverley,et al.  Contributions of dendritic spines and perforated synapses to synaptic plasticity , 1990, Brain Research Reviews.

[7]  R. Nicoll,et al.  Postsynaptic contribution to long-term potentiation revealed by the analysis of miniature synaptic currents , 1992, Nature.

[8]  K. 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. , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[10]  N. Tamamaki,et al.  Hippocampal pyramidal cells excite inhibitory neurons through a single release site , 1993, Nature.

[11]  T. Murphy,et al.  Visualization of quantal synaptic transmission by dendritic calcium imaging. , 1994, Science.

[12]  Kristen M. Harris,et al.  CHAPTER 18 – Serial Electron Microscopy as an Alternative or Complement to Confocal Microscopy for the Study of Synapses and Dendritic Spines in the Central Nervous System , 1994 .

[13]  J. Pierce,et al.  An ultrastructural size principle , 1994, Neuroscience.

[14]  P Andersen,et al.  Analysis of dendritic spines in rat CA1 pyramidal cells intracellularly filled with a fluorescent dye , 1995, The Journal of comparative neurology.

[15]  E. Neher,et al.  The use of fura-2 for estimating ca buffers and ca fluxes , 1995, Neuropharmacology.

[16]  D. Rusakov,et al.  Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  J. Connor,et al.  Micromolar Ca2+ transients in dendritic spines of hippocampal pyramidal neurons in brain slice , 1995, Neuron.

[18]  Martin Wilson,et al.  Variation in GABA mini amplitude is the consequence of variation in transmitter concentration , 1995, Neuron.

[19]  F. Edwards,et al.  Anatomy and electrophysiology of fast central synapses lead to a structural model for long-term potentiation. , 1995, Physiological reviews.

[20]  M. Segal,et al.  Morphological analysis of dendritic spine development in primary cultures of hippocampal neurons , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  T. Murphy,et al.  Mapping miniature synaptic currents to single synapses using calcium imaging reveals heterogeneity in postsynaptic output , 1995, Neuron.

[22]  W. Denk,et al.  Dendritic spines as basic functional units of neuronal integration , 1995, Nature.

[23]  K. Harris,et al.  Variation in the number, location and size of synaptic vesicles provides an anatomical basis for the nonuniform probability of release at hippocampal CA1 synapses , 1995, Neuropharmacology.

[24]  M. Segal,et al.  Morphological plasticity in dendritic spines of cultured hippocampal neurons , 1996, Neuroscience.

[25]  Timothy H. Murphy,et al.  Ca2+ Imaging of CNS Axons in Culture Indicates Reliable Coupling between Single Action Potentials and Distal Functional Release Sites , 1996, Neuron.

[26]  P. Somogyi,et al.  Effect, number and location of synapses made by single pyramidal cells onto aspiny interneurones of cat visual cortex. , 1997, The Journal of physiology.

[27]  M. Trommald,et al.  Dimensions and density of dendritic spines from rat dentate granule cells based on reconstructions from serial electron micrographs , 1997, The Journal of comparative neurology.

[28]  Mark Farrant,et al.  Differences in Synaptic GABAA Receptor Number Underlie Variation in GABA Mini Amplitude , 1997, Neuron.

[29]  Peter Somogyi,et al.  Erratum: Diverse sources of hippocampal unitary inhibitory postsynaptic potentials and the number of synaptic release sites (Nature (1994) 368 (823- 828)) , 1997 .

[30]  Mary B. Kennedy,et al.  The postsynaptic density at glutamatergic synapses , 1997, Trends in Neurosciences.

[31]  T. Schikorski,et al.  Quantitative Ultrastructural Analysis of Hippocampal Excitatory Synapses Materials and Methods Terminology Fixation and Embedding , 2022 .

[32]  Alain Marty,et al.  Heterogeneity of Functional Synaptic Parameters among Single Release Sites , 1997, Neuron.

[33]  P. Andersen,et al.  Spatial training in a complex environment and isolation alter the spine distribution differently in rat CA1 pyramidal cells. , 1997, The Journal of comparative neurology.

[34]  T. Bliss,et al.  Ultrastructural synaptic correlates of spatial learning in rat hippocampus , 1997, Neuroscience.

[35]  M. Sheng.  Excitatory synapses. Glutamate receptors put in their place. , 1997, Nature.

[36]  M. Sheng.  Glutamate receptors put in their place , 1997, Nature.

[37]  Ann Marie Craig,et al.  Activity Regulates the Synaptic Localization of the NMDA Receptor in Hippocampal Neurons , 1997, Neuron.

[38]  Peter Somogyi,et al.  Cell Type and Pathway Dependence of Synaptic AMPA Receptor Number and Variability in the Hippocampus , 1998, Neuron.

[39]  D. Clapham,et al.  NMDA receptors amplify calcium influx into dendritic spines during associative pre- and postsynaptic activation , 1998, Nature Neuroscience.

[40]  Alain Marty,et al.  Multivesicular Release at Single Functional Synaptic Sites in Cerebellar Stellate and Basket Cells , 1998, The Journal of Neuroscience.

[41]  T. Schikorski,et al.  Comparison of Hippocampal Dendritic Spines in Culture and in Brain , 1998, The Journal of Neuroscience.

[42]  K M Harris,et al.  Stability in Synapse Number and Size at 2 Hr after Long-Term Potentiation in Hippocampal Area CA1 , 1998, The Journal of Neuroscience.

[43]  O. Prange,et al.  Analysis of multiquantal transmitter release from single cultured cortical neuron terminals. , 1999, Journal of neurophysiology.

[44]  W. Denk,et al.  Mechanisms of Calcium Influx into Hippocampal Spines: Heterogeneity among Spines, Coincidence Detection by NMDA Receptors, and Optical Quantal Analysis , 1999, The Journal of Neuroscience.

[45]  T. Bliss,et al.  Single Synaptic Events Evoke NMDA Receptor–Mediated Release of Calcium from Internal Stores in Hippocampal Dendritic Spines , 1999, Neuron.