Estimating the Time Course of the Excitatory Synaptic Conductance in Neocortical Pyramidal Cells Using a Novel Voltage Jump Method

We introduce a method that permits faithful extraction of the decay time course of the synaptic conductance independent of dendritic geometry and the electrotonic location of the synapse. The method is based on the experimental procedure of Pearce (1993), consisting of a series of identical somatic voltage jumps repeated at various times relative to the onset of the synaptic conductance. The progression of synaptic charge recovered by successive jumps has a characteristic shape, which can be described by an analytical function consisting of sums of exponentials. The voltage jump method was tested with simulations using simple equivalent cylinder cable models as well as detailed compartmental models of pyramidal cells. The decay time course of the synaptic conductance could be estimated with high accuracy, even with high series resistances, low membrane resistances, and electrotonically remote, distributed synapses. The method also provides the time course of the voltage change at the synapse in response to a somatic voltage-clamp step and thus may be useful for constraining compartmental models and estimating the relative electrotonic distance of synapses. In conjunction with an estimate of the attenuation of synaptic charge, the method also permits recovery of the amplitude of the synaptic conductance. We use the method experimentally to determine the decay time course of excitatory synaptic conductances in neocortical pyramidal cells. The relatively rapid decay time constant we have estimated (τ ∼1.7 msec at 35°C) has important consequences for dendritic integration of synaptic input by these neurons.

[1]  W. Rall Distinguishing theoretical synaptic potentials computed for different soma-dendritic distributions of synaptic input. , 1967, Journal of neurophysiology.

[2]  R. B. Wuerker,et al.  Membrane impedance changes during synaptic transmission in cat spinal motoneurons. , 1967, Journal of neurophysiology.

[3]  W. Rall Time constants and electrotonic length of membrane cylinders and neurons. , 1969, Biophysical journal.

[4]  A. Peters,et al.  The small pyramidal neuron of the rat cerebral cortex. The perikaryon, dendrites and spines. , 1970, The American journal of anatomy.

[5]  S. Redman The attenuation of passively propagating dendritic potentials in a motoneurone cable model , 1973, The Journal of physiology.

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

[7]  J Rinzel,et al.  Transient response in a dendritic neuron model for current injected at one branch. , 1974, Biophysical journal.

[8]  C. Nicholson Electric current flow in excitable cells J. J. B. Jack, D. Noble &R. W. Tsien Clarendon Press, Oxford (1975). 502 pp., £18.00 , 1976, Neuroscience.

[9]  S. Provencher A Fourier method for the analysis of exponential decay curves. , 1976, Biophysical journal.

[10]  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.

[11]  N T Carnevale,et al.  Electrophysiological characterization of remote chemical synapses. , 1982, Journal of neurophysiology.

[12]  T. H. Brown,et al.  Interpretation of voltage-clamp measurements in hippocampal neurons. , 1983, Journal of neurophysiology.

[13]  S J Redman,et al.  The synaptic current evoked in cat spinal motoneurones by impulses in single group 1a axons. , 1983, The Journal of physiology.

[14]  Idan Segev,et al.  Space-Clamp Problems When Voltage Clamping Branched Neurons With Intracellular Microelectrodes , 1985 .

[15]  William H. Press,et al.  Numerical recipes in C. The art of scientific computing , 1987 .

[16]  G. Westbrook,et al.  Synaptic excitation in cultures of mouse spinal cord neurones: receptor pharmacology and behaviour of synaptic currents. , 1986, The Journal of physiology.

[17]  F. A. Seiler,et al.  Numerical Recipes in C: The Art of Scientific Computing , 1989 .

[18]  R. Nicoll,et al.  Analysis of excitatory synaptic action in pyramidal cells using whole‐cell recording from rat hippocampal slices. , 1990, The Journal of physiology.

[19]  Moshe Abeles,et al.  Corticonics: Neural Circuits of Cerebral Cortex , 1991 .

[20]  A. Konnerth,et al.  Synaptic‐ and agonist‐induced excitatory currents of Purkinje cells in rat cerebellar slices. , 1991, The Journal of physiology.

[21]  R. Silver,et al.  Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses in situ , 1992, Nature.

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

[23]  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.

[24]  I. Forsythe,et al.  The binaural auditory pathway: excitatory amino acid receptors mediate dual timecourse excitatory postsynaptic currents in the rat medial nucleus of the trapezoid body , 1993, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[25]  Michael L. Hines,et al.  NEURON — A Program for Simulation of Nerve Equations , 1993 .

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

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

[28]  N. Spruston,et al.  Voltage- and space-clamp errors associated with the measurement of electrotonically remote synaptic events. , 1993, Journal of neurophysiology.

[29]  Robert A. Pearce,et al.  Physiological evidence for two distinct GABAA responses in rat hippocampus , 1993, Neuron.

[30]  P. Jonas,et al.  Na(+)‐activated K+ channels localized in the nodal region of myelinated axons of Xenopus. , 1994, The Journal of physiology.

[31]  William R. Softky,et al.  Sub-millisecond coincidence detection in active dendritic trees , 1994, Neuroscience.

[32]  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.

[33]  Boris Barbour,et al.  Prolonged presence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cells , 1994, Neuron.

[34]  Daniel Johnston,et al.  Dendritic attenuation of synaptic potentials and currents: the role of passive membrane properties , 1994, Trends in Neurosciences.

[35]  L. Trussell,et al.  Voltage clamp analysis of excitatory synaptic transmission in the avian nucleus magnocellularis. , 1994, The Journal of physiology.

[36]  J. C. Lodder,et al.  Large amplitude variability of GABAergic IPSCs in melanotropes from Xenopus laevis: evidence that quantal size differs between synapses. , 1994, Journal of neurophysiology.

[37]  B. Sakmann,et al.  Differences in Ca2+ permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential GluR-B subunit expression , 1994, Neuron.

[38]  Ra Silver,et al.  Filtering of the synaptic current estimated from the timecourse from NMDA channel opening. , 1995 .

[39]  B. Sakmann,et al.  Amplification of EPSPs by axosomatic sodium channels in neocortical pyramidal neurons , 1995, Neuron.

[40]  I. Módy,et al.  Tonic inhibition originates from synapses close to the soma , 1995, Neuron.

[41]  D. Rossi,et al.  Properties of transmission at a giant glutamatergic synapse in cerebellum: the mossy fiber-unipolar brush cell synapse. , 1995, Journal of neurophysiology.

[42]  S. Mennerick,et al.  Presynaptic influence on the time course of fast excitatory synaptic currents in cultured hippocampal cells , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[43]  M. Morales,et al.  Selective antagonism of AMPA receptors unmasks kainate receptor-mediated responses in hippocampal neurons , 1995, Neuron.

[44]  B. Walmsley,et al.  Receptors underlying excitatory synaptic transmission in slices of the rat anteroventral cochlear nucleus. , 1995, Journal of neurophysiology.

[45]  A. Constanti,et al.  Mechanism of block by ZD 7288 of the hyperpolarization-activated inward rectifying current in guinea pig substantia nigra neurons in vitro. , 1995, Journal of neurophysiology.

[46]  Y. Yaari,et al.  Synaptic NMDA receptors in developing mouse hippocampal neurones: functional properties and sensitivity to ifenprodil. , 1996, The Journal of physiology.

[47]  J M Bekkers,et al.  Apical Dendritic Location of Slow Afterhyperpolarization Current in Hippocampal Pyramidal Neurons: Implications for the Integration of Long-Term Potentiation , 1996, The Journal of Neuroscience.

[48]  N T Carnevale,et al.  Electrotonic architecture of hippocampal CA1 pyramidal neurons based on three-dimensional reconstructions. , 1996, Journal of neurophysiology.

[49]  W. Singer,et al.  Integrator or coincidence detector? The role of the cortical neuron revisited , 1996, Trends in Neurosciences.

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

[51]  D Colquhoun,et al.  Deactivation and desensitization of non‐NMDA receptors in patches and the time course of EPSCs in rat cerebellar granule cells. , 1996, The Journal of physiology.

[52]  T. Freund,et al.  Differences between Somatic and Dendritic Inhibition in the Hippocampus , 1996, Neuron.

[53]  T. Sejnowski,et al.  [Letters to nature] , 1996, Nature.

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

[55]  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.