Quantal Analysis Reveals a Functional Correlation between Presynaptic and Postsynaptic Efficacy in Excitatory Connections from Rat Neocortex

At many central synapses, the presynaptic bouton and postsynaptic density are structurally correlated. However, it is unknown whether this correlation extends to the functional properties of the synapses. To investigate this, we made recordings from synaptically coupled pairs of pyramidal neurons in rat visual cortex. The mean peak amplitude of EPSPs recorded from pairs of L2/3 neurons ranged between 40 μV and 2.9 mV. EPSP rise times were consistent with the majority of the synapses being located on basal dendrites; this was confirmed by full anatomical reconstructions of a subset of connected pairs. Over a third of the connections could be described using a quantal model that assumed simple binomial statistics. Release probability (Pr) and quantal size (Q), as measured at the somatic recording site, showed considerable heterogeneity between connections. However, across the population of connections, values of Pr and Q for individual connections were positively correlated with one another. This correlation also held for inputs to layer 5 pyramidal neurons from both layer 2/3 and neighboring layer 5 pyramidal neurons, suggesting that during development of cortical connections presynaptic and postsynaptic strengths are dependently scaled. For 2/3 to 2/3 connections, mean EPSP amplitude was correlated with both Q and Pr values but uncorrelated with N, the number of functional release sites mediating the connection. The efficacy of a cortical connection is thus set by coordinated presynaptic and postsynaptic strength.

[1]  W. Rall Membrane potential transients and membrane time constant of motoneurons. , 1960, Experimental neurology.

[2]  H Korn,et al.  Fluctuating responses at a central synapse: n of binomial fit predicts number of stained presynaptic boutons. , 1981, Science.

[3]  J. Jack,et al.  The components of synaptic potentials evoked in cat spinal motoneurones by impulses in single group Ia afferents. , 1981, The Journal of physiology.

[4]  G. Major,et al.  The modelling of pyramidal neurones in the visual cortex , 1989 .

[5]  A. Peters,et al.  Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. I. Morphometric analysis , 1990, Journal of neurocytology.

[6]  H. Korn,et al.  Size and shape of glycine receptor clusters in a central neuron exhibit a somato-dendritic gradient. , 1990, The New biologist.

[7]  A. Peters,et al.  Different kinds of axon terminals forming symmetric synapses with the cell bodies and initial axon segments of layer II/III pyramidal cells. II. Synaptic junctions , 1990, Journal of neurocytology.

[8]  A. Larkman Dendritic morphology of pyramidal neurones of the visual cortex of the rat: I. Branching patterns , 1991, The Journal of comparative neurology.

[9]  A. Larkman,et al.  Dendritic morphology of pyramidal neurones of the visual cortex of the rat: III. Spine distributions , 1991, The Journal of comparative neurology.

[10]  H Korn,et al.  Intrinsic quantal variability due to stochastic properties of receptor-transmitter interactions. , 1992, Science.

[11]  J J Jack,et al.  Dendritic morphology of pyramidal neurones of the visual cortex of the rat. IV: Electrical geometry , 1992, The Journal of comparative neurology.

[12]  J J Jack,et al.  Solutions for transients in arbitrarily branching cables: II. Voltage clamp theory. , 1993, Biophysical journal.

[13]  G. Major,et al.  Solutions for transients in arbitrarily branching cables: III. Voltage clamp problems. , 1993, Biophysical journal.

[14]  K M Harris,et al.  Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1 , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[16]  G. Major,et al.  Quantal analysis of the synaptic excitation of CA1 hippocampal pyramidal cells. , 1994, Advances in second messenger and phosphoprotein research.

[17]  B Sakmann,et al.  Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  D. Daley,et al.  Statistical analysis of synaptic transmission: model discrimination and confidence limits. , 1994, Biophysical journal.

[19]  J J Jack,et al.  The variance of successive peaks in synaptic amplitude histograms: effects of inter-site differences in quantal size , 1995, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[20]  C. Stevens,et al.  Quantal analysis of EPSCs recorded from small numbers of synapses in hippocampal cultures. , 1995, Journal of neurophysiology.

[21]  S. Redman,et al.  Statistical analysis of amplitude fluctuations in EPSCs evoked in rat CA1 pyramidal neurones in vitro. , 1996, The Journal of physiology.

[22]  T. Tsumoto,et al.  Quantal analysis suggests presynaptic involvement in expression of neocortical short- and long-term depression. , 1997, Neuroscience.

[23]  J J Jack,et al.  Quantal analysis of excitatory synapses in rat hippocampal CA1 In Vitro during low‐frequency depression , 1997, The Journal of physiology.

[24]  N. Seidah,et al.  Regulation by gastric acid of the processing of progastrin‐derived peptides in rat antral mucosa , 1997, The Journal of physiology.

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

[26]  F. J. Alvarez,et al.  Cell‐type specific organization of glycine receptor clusters in the mammalian spinal cord , 1997, The Journal of comparative neurology.

[27]  H. Markram,et al.  Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex. , 1997, The Journal of physiology.

[28]  K. Stratford,et al.  Calibration of an autocorrelation‐based method for determining amplitude histogram reliability and quantal size , 1997, The Journal of physiology.

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

[30]  Mark J. Wall,et al.  Development of the quantal properties of evoked and spontaneous synaptic currents at a brain synapse , 1998, Nature Neuroscience.

[31]  B. Walmsley,et al.  Diversity of structure and function at mammalian central synapses , 1998, Trends in Neurosciences.

[32]  A. Larkman,et al.  The reliability of excitatory synaptic transmission in slices of rat visual cortex in vitro is temperature dependent , 1998, The Journal of physiology.

[33]  N. Spruston,et al.  Determinants of Voltage Attenuation in Neocortical Pyramidal Neuron Dendrites , 1998, The Journal of Neuroscience.

[34]  B. Walmsley,et al.  Quantal size is correlated with receptor cluster area at glycinergic synapses in the rat brainstem , 1999, The Journal of physiology.

[35]  Petter Laake,et al.  Different modes of expression of AMPA and NMDA receptors in hippocampal synapses , 1999, Nature Neuroscience.

[36]  B. Sakmann,et al.  Developmental Switch in the Short-Term Modification of Unitary EPSPs Evoked in Layer 2/3 and Layer 5 Pyramidal Neurons of Rat Neocortex , 1999, The Journal of Neuroscience.

[37]  C F Stevens,et al.  Quantitative fine-structural analysis of olfactory cortical synapses. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  R. Tsien,et al.  Variability of Neurotransmitter Concentration and Nonsaturation of Postsynaptic AMPA Receptors at Synapses in Hippocampal Cultures and Slices , 1999, Neuron.

[39]  C F Stevens,et al.  Nonsaturation of AMPA and NMDA receptors at hippocampal synapses. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[40]  J. Magee,et al.  Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons , 2000, Nature Neuroscience.

[41]  B. Sakmann,et al.  Calcium dynamics associated with action potentials in single nerve terminals of pyramidal cells in layer 2/3 of the young rat neocortex , 2000, The Journal of physiology.

[42]  T. Schikorski,et al.  Inactivity Produces Increases in Neurotransmitter Release and Synapse Size , 2001, Neuron.

[43]  C. Jahr,et al.  Multivesicular Release at Climbing Fiber-Purkinje Cell Synapses , 2001, Neuron.

[44]  B. Gustafsson,et al.  Quantal variability at glutamatergic synapses in area CA1 of the rat neonatal hippocampus , 2001, The Journal of physiology.

[45]  J. Magee,et al.  Distance-Dependent Increase in AMPA Receptor Number in the Dendrites of Adult Hippocampal CA1 Pyramidal Neurons , 2001, The Journal of Neuroscience.

[46]  J. Jack,et al.  Detailed passive cable models of layer 2/3 pyramidal cells in rat visual cortex at different temperatures , 2002, The Journal of physiology.

[47]  G. Stuart,et al.  Dependence of EPSP Efficacy on Synapse Location in Neocortical Pyramidal Neurons , 2002, Science.

[48]  K. Svoboda,et al.  Facilitation at single synapses probed with optical quantal analysis , 2002, Nature Neuroscience.

[49]  J. C. Nelson,et al.  Excitatory inputs to spiny cells in layers 4 and 6 of cat striate cortex. , 2002, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[50]  R. Silver,et al.  High-Probability Uniquantal Transmission at Excitatory Synapses in Barrel Cortex , 2003, Science.

[51]  S. Rumpel,et al.  Silent synapses in the immature visual cortex: layer-specific developmental regulation. , 2004, Journal of neurophysiology.

[52]  L. Marin,et al.  Ultrastructure of synapses with different transmitter-releasing characteristics on motor axon terminals of a crab, Hyas areneas , 2004, Cell and Tissue Research.

[53]  D. Johnston,et al.  Target Cell-Dependent Normalization of Transmitter Release at Neocortical Synapses , 2005, Science.

[54]  Z. Nusser,et al.  Quantal Size Is Independent of the Release Probability at Hippocampal Excitatory Synapses , 2005, The Journal of Neuroscience.

[55]  R. Tsien,et al.  Adaptation to Synaptic Inactivity in Hippocampal Neurons , 2005, Neuron.

[56]  H. Kasai,et al.  Number and Density of AMPA Receptors in Single Synapses in Immature Cerebellum , 2005, The Journal of Neuroscience.

[57]  J. Lübke,et al.  Efficacy and connectivity of intracolumnar pairs of layer 2/3 pyramidal cells in the barrel cortex of juvenile rats , 2006, The Journal of physiology.

[58]  Nelson Spruston,et al.  Distance-Dependent Differences in Synapse Number and AMPA Receptor Expression in Hippocampal CA1 Pyramidal Neurons , 2006, Neuron.

[59]  Jenny C A Read,et al.  Extracellular Calcium Regulates Postsynaptic Efficacy through Group 1 Metabotropic Glutamate Receptors , 2006, The Journal of Neuroscience.

[60]  C. Jahr,et al.  Multivesicular Release at Schaffer Collateral–CA1 Hippocampal Synapses , 2006, The Journal of Neuroscience.

[61]  Kevin Fox,et al.  The Role of Nitric Oxide and GluR1 in Presynaptic and Postsynaptic Components of Neocortical Potentiation , 2006, The Journal of Neuroscience.

[62]  J. Lübke,et al.  The morphology of excitatory central synapses: from structure to function , 2006, Cell and Tissue Research.

[63]  K. Fox,et al.  Presynaptic efficacy directs normalization of synaptic strength in layer 2/3 rat neocortex after paired activity. , 2007, Journal of neurophysiology.

[64]  Alex M Thomson,et al.  Binomial parameters differ across neocortical layers and with different classes of connections in adult rat and cat neocortex , 2007, Proceedings of the National Academy of Sciences.

[65]  A. Polsky,et al.  Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study , 2007, Nature Neuroscience.

[66]  David Hinkley,et al.  Bootstrap Methods: Another Look at the Jackknife , 2008 .

[67]  Y. Goda,et al.  Activity-dependent coordination of presynaptic release probability and postsynaptic GluR2 abundance at single synapses , 2008, Proceedings of the National Academy of Sciences.

[68]  M. J. Friedlander,et al.  Synaptic Output of Individual Layer 4 Neurons in Guinea Pig Visual Cortex , 2009, The Journal of Neuroscience.