Dendritic amplification of inhibitory postsynaptic potentials in a model Purkinje cell

In neurons with large dendritic arbors, the postsynaptic potentials interact in a complex manner with active and passive membrane properties, causing not easily predictable transformations during the propagation from synapse to soma. Previous theoretical and experimental studies in both cerebellar Purkinje cells and neocortical pyramidal neurons have shown that voltage‐dependent ion channels change the amplitude and time‐course of postsynaptic potentials. We investigated the mechanisms involved in the propagation of inhibitory postsynaptic potentials (IPSPs) along active dendrites in a model of the Purkinje cell. The amplitude and time‐course of IPSPs recorded at the soma were dependent on the synaptic distance from the soma, as predicted by passive cable theory. We show that the effect of distance on the amplitude and width of the IPSP was significantly reduced by the dendritic ion channels, whereas the rise time was not affected. Somatic IPSPs evoked by the activation of the most distal synapses were up to six times amplified owing to the presence of voltage‐gated channels and the IPSP width became independent of the covered distance. A transient deactivation of the Ca2+ channels and the Ca2+‐dependent K+ channels, triggered by the hyperpolarization following activation of the inhibitory synapse, was found to be responsible for these dynamics. Nevertheless, the position of activated synapses had a marked effect on the Purkinje cell firing pattern, making stellate cells and basket cells most suitable for controlling the firing rate and spike timing, respectively, of their target Purkinje cells.

[1]  J. Bower,et al.  An active membrane model of the cerebellar Purkinje cell. I. Simulation of current clamps in slice. , 1994, Journal of neurophysiology.

[2]  J. Bower,et al.  An active membrane model of the cerebellar Purkinje cell II. Simulation of synaptic responses. , 1994, Journal of neurophysiology.

[3]  James M. Bower,et al.  The Book of GENESIS , 1994, Springer New York.

[4]  M. Häusser,et al.  Compartmental models of rat cerebellar Purkinje cells based on simultaneous somatic and dendritic patch‐clamp recordings , 2001, The Journal of physiology.

[5]  G. Stuart,et al.  Role of dendritic synapse location in the control of action potential output , 2003, Trends in Neurosciences.

[6]  B. Barbour Synaptic currents evoked in purkinje cells by stimulating individual granule cells , 1993, Neuron.

[7]  E. De Schutter,et al.  Dendritic voltage and calcium-gated channels amplify the variability of postsynaptic responses in a Purkinje cell model. , 1998, Journal of neurophysiology.

[8]  M. Kano,et al.  GABAergic activation of an inwardly rectifying K+ current in mouse cerebellar Purkinje cells , 2005, The Journal of physiology.

[9]  B. Barbour,et al.  Properties of Unitary Granule Cell→Purkinje Cell Synapses in Adult Rat Cerebellar Slices , 2002, The Journal of Neuroscience.

[10]  Erik De Schutter,et al.  Computational neuroscience : realistic modeling for experimentalists , 2000 .

[11]  Peter Somogyi,et al.  Cell surface domain specific postsynaptic currents evoked by identified GABAergic neurones in rat hippocampus in vitro , 2000, The Journal of physiology.

[12]  Erik De Schutter,et al.  Synchronization of Purkinje Cell Pairs Along the Parallel Fiber Axis: A Modeling Study , 2002, Neurocomputing.

[13]  M. Larkum,et al.  High I(h) channel density in the distal apical dendrite of layer V pyramidal cells increases bidirectional attenuation of EPSPs. , 2001, Journal of neurophysiology.

[14]  Y Yarom,et al.  Physiology, morphology and detailed passive models of guinea‐pig cerebellar Purkinje cells. , 1994, The Journal of physiology.

[15]  H. Sompolinsky,et al.  Bistability of cerebellar Purkinje cells modulated by sensory stimulation , 2005, Nature Neuroscience.

[16]  D. Armstrong,et al.  Activity patterns of cerebellar cortical neurones and climbing fibre afferents in the awake cat. , 1979, The Journal of physiology.

[17]  Prof. Dr. Sanford L. Palay,et al.  Cerebellar Cortex , 1974, Springer Berlin Heidelberg.

[18]  J M Bower,et al.  Quantitative Golgi study of the rat cerebellar molecular layer interneurons using principal component analysis , 1998, The Journal of comparative neurology.

[19]  C. Pouzat,et al.  Developmental Regulation of Basket/Stellate Cell→Purkinje Cell Synapses in the Cerebellum , 1997, The Journal of Neuroscience.

[20]  A. Aertsen,et al.  Neuronal Integration of Synaptic Input in the Fluctuation-Driven Regime , 2004, The Journal of Neuroscience.

[21]  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.

[22]  J. Eccles The cerebellum as a computer: patterns in space and time. , 1973, The Journal of physiology.

[23]  A Konnerth,et al.  Localized calcium signalling and neuronal integration in cerebellar Purkinje neurones. , 1996, Cell calcium.

[24]  J. Bower,et al.  Simulated responses of cerebellar Purkinje cells are independent of the dendritic location of granule cell synaptic inputs. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  W. Rall Cable theory for dendritic neurons , 1989 .

[26]  F. Edwards,et al.  Serotonin Drives a Novel GABAergic Synaptic Current Recorded in Rat Cerebellar Purkinje Cells: A Lugaro Cell to Purkinje Cell Synapse , 2003, The Journal of Neuroscience.

[27]  Andreas Zimmer,et al.  The Cannabinoid CB1 Receptor Mediates Retrograde Signals for Depolarization-Induced Suppression of Inhibition in Cerebellar Purkinje Cells , 2002, The Journal of Neuroscience.

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

[29]  C. Koch,et al.  Amplification and linearization of distal synaptic input to cortical pyramidal cells. , 1994, Journal of neurophysiology.

[30]  Christof Koch,et al.  The role of single neurons in information processing , 2000, Nature Neuroscience.

[31]  D. Johnston,et al.  Active dendrites reduce location-dependent variability of synaptic input trains. , 1997, Journal of neurophysiology.

[32]  Erik De Schutter,et al.  Modeling Simple and Complex Active Neurons , 2000 .

[33]  J M Bower,et al.  The Role of Synaptic and Voltage-Gated Currents in the Control of Purkinje Cell Spiking: A Modeling Study , 1997, The Journal of Neuroscience.

[34]  M. Häusser,et al.  Integration of quanta in cerebellar granule cells during sensory processing , 2004, Nature.

[35]  R. Harvey,et al.  Quantitatives studies on the mammalian cerebellum , 1991, Progress in Neurobiology.

[36]  G. Stuart,et al.  Voltage- and Site-Dependent Control of the Somatic Impact of Dendritic IPSPs , 2003, The Journal of Neuroscience.

[37]  F. Crépel,et al.  Inward rectification and low threshold calcium conductance in rat cerebellar Purkinje cells. An in vitro study. , 1986, The Journal of physiology.

[38]  R. G. Willison,et al.  Excitatory synaptic mechanisms , 1971 .

[39]  M. Häusser,et al.  Tonic Synaptic Inhibition Modulates Neuronal Output Pattern and Spatiotemporal Synaptic Integration , 1997, Neuron.

[40]  Erik De Schutter,et al.  Effects of variability in anatomical reconstruction techniques on models of synaptic integration by dendrites: a comparison of three internet archives , 2004, The European journal of neuroscience.

[41]  J M Bower,et al.  Synaptic Control of Spiking in Cerebellar Purkinje Cells: Dynamic Current Clamp Based on Model Conductances , 1999, The Journal of Neuroscience.