Accurate and Fast Simulation of Channel Noise in Conductance-Based Model Neurons by Diffusion Approximation

Stochastic channel gating is the major source of intrinsic neuronal noise whose functional consequences at the microcircuit- and network-levels have been only partly explored. A systematic study of this channel noise in large ensembles of biophysically detailed model neurons calls for the availability of fast numerical methods. In fact, exact techniques employ the microscopic simulation of the random opening and closing of individual ion channels, usually based on Markov models, whose computational loads are prohibitive for next generation massive computer models of the brain. In this work, we operatively define a procedure for translating any Markov model describing voltage- or ligand-gated membrane ion-conductances into an effective stochastic version, whose computer simulation is efficient, without compromising accuracy. Our approximation is based on an improved Langevin-like approach, which employs stochastic differential equations and no Montecarlo methods. As opposed to an earlier proposal recently debated in the literature, our approximation reproduces accurately the statistical properties of the exact microscopic simulations, under a variety of conditions, from spontaneous to evoked response features. In addition, our method is not restricted to the Hodgkin-Huxley sodium and potassium currents and is general for a variety of voltage- and ligand-gated ion currents. As a by-product, the analysis of the properties emerging in exact Markov schemes by standard probability calculus enables us for the first time to analytically identify the sources of inaccuracy of the previous proposal, while providing solid ground for its modification and improvement we present here.

[1]  J W Moore,et al.  On numerical integration of the Hodgkin and Huxley equations for a membrane action potential. , 1974, Journal of theoretical biology.

[2]  Marifi Güler Erratum: Dissipative stochastic mechanics for capturing neuronal dynamics under the influence of ion channel noise: Formalism using a special membrane [Phys. Rev. E76, 041918 (2007)] , 2010 .

[3]  Cian O'Donnell,et al.  Stochastic Ion Channel Gating in Dendritic Neurons: Morphology Dependence and Probabilistic Synaptic Activation of Dendritic Spikes , 2010, PLoS Comput. Biol..

[4]  H. Markram,et al.  Disynaptic Inhibition between Neocortical Pyramidal Cells Mediated by Martinotti Cells , 2007, Neuron.

[5]  Athanasios Papoulis,et al.  Probability, Random Variables and Stochastic Processes , 1965 .

[6]  Zdzislaw Bubnicki,et al.  Modern Control Theory , 2005 .

[7]  Ian C. Bruce,et al.  Evaluation of Stochastic Differential Equation Approximation of Ion Channel Gating Models , 2009, Annals of Biomedical Engineering.

[8]  Nicholas T. Carnevale,et al.  ModelDB: A Database to Support Computational Neuroscience , 2004, Journal of Computational Neuroscience.

[9]  Peter Lancaster,et al.  The theory of matrices , 1969 .

[10]  J. E. Glynn,et al.  Numerical Recipes: The Art of Scientific Computing , 1989 .

[11]  Carson C. Chow,et al.  Spontaneous action potentials due to channel fluctuations. , 1996, Biophysical journal.

[12]  Olli Yli-Harja,et al.  Stochastic Differential Equation Model for Cerebellar Granule Cell Excitability , 2008, PLoS Comput. Biol..

[13]  F. R. Gantmakher The Theory of Matrices , 1984 .

[14]  I. Miller Probability, Random Variables, and Stochastic Processes , 1966 .

[15]  C. Koch,et al.  Multiple channels and calcium dynamics , 1989 .

[16]  J. R. Clay,et al.  Relationship between membrane excitability and single channel open-close kinetics. , 1983, Biophysical journal.

[17]  J. Ruppersberg Ion Channels in Excitable Membranes , 1996 .

[18]  Terrence J. Sejnowski,et al.  Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism , 1994, Journal of Computational Neuroscience.

[19]  Ian C. Bruce,et al.  Implementation Issues in Approximate Methods for Stochastic Hodgkin–Huxley Models , 2007, Annals of Biomedical Engineering.

[20]  J. White,et al.  Channel noise in neurons , 2000, Trends in Neurosciences.

[21]  Paul J. Abbas,et al.  Effects of electrode-to-fiber distance on temporal neural response with electrical stimulation , 2004, IEEE Transactions on Biomedical Engineering.

[22]  M. White,et al.  A stochastic model of the electrically stimulated auditory nerve: pulse-train response , 1999, IEEE Transactions on Biomedical Engineering.

[23]  A. Bacci,et al.  Enhancement of Spike-Timing Precision by Autaptic Transmission in Neocortical Inhibitory Interneurons , 2006, Neuron.

[24]  H. Mino,et al.  Effects of Neural Refractoriness on Spatio–Temporal Variability in Spike Initiations With Electrical Stimulation , 2006, IEEE Transactions on Neural Systems and Rehabilitation Engineering.

[25]  Lawrence Sirovich,et al.  The Approach of a Neuron Population Firing Rate to a New Equilibrium: An Exact Theoretical Result , 2000, Neural Computation.

[26]  Peter Dayan,et al.  Theoretical Neuroscience: Computational and Mathematical Modeling of Neural Systems , 2001 .

[27]  F Bezanilla,et al.  A sodium channel gating model based on single channel, macroscopic ionic, and gating currents in the squid giant axon. , 1991, Biophysical journal.

[28]  David R. Cox,et al.  The Theory of Stochastic Processes , 1967, The Mathematical Gazette.

[29]  Michele Giugliano,et al.  The response of cortical neurons to in vivo-like input current: theory and experiment , 2008, Biological Cybernetics.

[30]  T. Sejnowski,et al.  Reliability of spike timing in neocortical neurons. , 1995, Science.

[31]  Erik De Schutter,et al.  Computational Modeling Methods for Neuroscientists , 2009 .

[32]  R. Fox Stochastic versions of the Hodgkin-Huxley equations. , 1997, Biophysical Journal.

[33]  Fox,et al.  Emergent collective behavior in large numbers of globally coupled independently stochastic ion channels. , 1994, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[34]  Michael L. Hines,et al.  Parallel network simulations with NEURON , 2006, Journal of Computational Neuroscience.

[35]  Duane Q. Nykamp,et al.  A Population Density Approach That Facilitates Large-Scale Modeling of Neural Networks: Extension to Slow Inhibitory Synapses , 2001, Neural Computation.

[36]  M. Gutnick,et al.  Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea‐pig neocortical neurones in slices. , 1996, The Journal of physiology.

[37]  Larry S. Liebovitch,et al.  Using fractals to understand the opening and closing of ion channels , 2006, Annals of Biomedical Engineering.

[38]  L. Walløe,et al.  Firing behaviour in a stochastic nerve membrane model based upon the Hodgkin-Huxley equations. , 1979, Acta physiologica Scandinavica.

[39]  A G Hawkes,et al.  The quality of maximum likelihood estimates of ion channel rate constants , 2003, The Journal of physiology.

[40]  Marifi Güler,et al.  Dissipative stochastic mechanics for capturing neuronal dynamics under the influence of ion channel noise: formalism using a special membrane. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[41]  Gillespie,et al.  Exact numerical simulation of the Ornstein-Uhlenbeck process and its integral. , 1996, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[42]  M B Jackson,et al.  Single‐Channel Recording , 1998, Current protocols in neuroscience.

[43]  J E Niven,et al.  Comparison of Langevin and Markov channel noise models for neuronal signal generation. , 2009, Physical review. E, Statistical, nonlinear, and soft matter physics.

[44]  Nicolas Brunel,et al.  Dynamics of the Firing Probability of Noisy Integrate-and-Fire Neurons , 2002, Neural Computation.

[45]  U. Karmarkar,et al.  Timing in the Absence of Clocks: Encoding Time in Neural Network States , 2007, Neuron.

[46]  A. Treves Mean-field analysis of neuronal spike dynamics , 1993 .

[47]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1952, The Journal of physiology.

[48]  Idan Segev,et al.  Ion Channel Stochasticity May Be Critical in Determining the Reliability and Precision of Spike Timing , 1998, Neural Computation.

[49]  Oren Shriki,et al.  Rate Models for Conductance-Based Cortical Neuronal Networks , 2003, Neural Computation.

[50]  Henry C. Tuckwell,et al.  Stochastic processes in the neurosciences , 1989 .

[51]  E Wanke,et al.  Channel noise in nerve membranes and lipid bilayers , 1975, Quarterly Reviews of Biophysics.

[52]  Jay T. Rubinstein,et al.  Response: Implementation Issues in Approximate Methods for Stochastic Hodgkin-Huxley models , 2006, Annals of Biomedical Engineering.

[53]  Huxley Af,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve. 1952. , 1990 .

[54]  Michael L. Hines,et al.  Fully implicit parallel simulation of single neurons , 2008, Journal of Computational Neuroscience.

[55]  T. L. Hill,et al.  Fluctuations and noise in kinetic systems. Application to K+ channels in the squid axon. , 1973, Biophysical journal.

[56]  L S Liebovitch,et al.  A model of ion channel kinetics using deterministic chaotic rather than stochastic processes. , 1991, Journal of theoretical biology.

[57]  A. Destexhe Kinetic Models of Synaptic Transmission , 1997 .

[58]  Lyle J. Graham,et al.  Efficient evaluation of neuron populations receiving colored-noise current based on a refractory density method. , 2008, Physical review. E, Statistical, nonlinear, and soft matter physics.

[59]  Thomas K. Berger,et al.  Evaluating automated parameter constraining procedures of neuron models by experimental and surrogate data , 2008, Biological Cybernetics.

[60]  H. Markram The Blue Brain Project , 2006, Nature Reviews Neuroscience.

[61]  Duane Q. Nykamp,et al.  A Population Density Approach That Facilitates Large-Scale Modeling of Neural Networks: Analysis and an Application to Orientation Tuning , 2004, Journal of Computational Neuroscience.

[62]  Micheal V. Mascagni Numerical methods for neuronal modeling , 1989 .

[63]  C. F. Stevens,et al.  A reinterpretation of mammalian sodium channel gating based on single channel recording , 1983, Nature.

[64]  Idan Segev,et al.  Methods in Neuronal Modeling , 1988 .

[65]  Jay T. Rubinstein,et al.  Comparison of Algorithms for the Simulation of Action Potentials with Stochastic Sodium Channels , 2002, Annals of Biomedical Engineering.

[66]  Christof Koch,et al.  Subthreshold voltage noise of rat neocortical pyramidal neurones , 2005, The Journal of physiology.

[67]  Hiroyuki Mino,et al.  Encoding of Information Into Neural Spike Trains in an Auditory Nerve Fiber Model With Electric Stimuli in the Presence of a Pseudospontaneous Activity , 2007, IEEE Transactions on Biomedical Engineering.

[68]  Lawrence Sirovich,et al.  On the Simulation of Large Populations of Neurons , 2004, Journal of Computational Neuroscience.

[69]  Michael L. Hines,et al.  The NEURON Book , 2006 .

[70]  D. Johnston,et al.  Foundations of Cellular Neurophysiology , 1994 .

[71]  Christof Koch,et al.  Subthreshold Voltage Noise Due to Channel Fluctuations in Active Neuronal Membranes , 2000, Journal of Computational Neuroscience.

[72]  Christof Koch,et al.  Detecting and Estimating Signals in Noisy Cable Structures, I: Neuronal Noise Sources , 1999, Neural Computation.