Motoneuron membrane potentials follow a time inhomogeneous jump diffusion process

Stochastic leaky integrate-and-fire models are popular due to their simplicity and statistical tractability. They have been widely applied to gain understanding of the underlying mechanisms for spike timing in neurons, and have served as building blocks for more elaborate models. Especially the Ornstein–Uhlenbeck process is popular to describe the stochastic fluctuations in the membrane potential of a neuron, but also other models like the square-root model or models with a non-linear drift are sometimes applied. Data that can be described by such models have to be stationary and thus, the simple models can only be applied over short time windows. However, experimental data show varying time constants, state dependent noise, a graded firing threshold and time-inhomogeneous input. In the present study we build a jump diffusion model that incorporates these features, and introduce a firing mechanism with a state dependent intensity. In addition, we suggest statistical methods to estimate all unknown quantities and apply these to analyze turtle motoneuron membrane potentials. Finally, simulated and real data are compared and discussed. We find that a square-root diffusion describes the data much better than an Ornstein–Uhlenbeck process with constant diffusion coefficient. Further, the membrane time constant decreases with increasing depolarization, as expected from the increase in synaptic conductance. The network activity, which the neuron is exposed to, can be reasonably estimated to be a threshold version of the nerve output from the network. Moreover, the spiking characteristics are well described by a Poisson spike train with an intensity depending exponentially on the membrane potential.

[1]  Jianfeng Feng,et al.  Maximum Likelihood Decoding of Neuronal Inputs from an Interspike Interval Distribution , 2009, Neural Computation.

[2]  A. Destexhe,et al.  The high-conductance state of neocortical neurons in vivo , 2003, Nature Reviews Neuroscience.

[3]  P Lánský,et al.  Input parameters in a one-dimensional neuronal model with reversal potentials. , 1998, Bio Systems.

[4]  W. Senn,et al.  Neocortical pyramidal cells respond as integrate-and-fire neurons to in vivo-like input currents. , 2003, Journal of neurophysiology.

[5]  Wulfram Gerstner,et al.  Spiking Neuron Models: An Introduction , 2002 .

[6]  R. Helmers,et al.  Estimating the intensity of a cyclic Poisson process in the presence of linear trend , 2009 .

[7]  A. Shiryaev,et al.  Limit Theorems for Stochastic Processes , 1987 .

[8]  Anthony N. Burkitt,et al.  A review of the integrate-and-fire neuron model: II. Inhomogeneous synaptic input and network properties , 2006, Biological Cybernetics.

[9]  Susanne Ditlevsen,et al.  Parameters of stochastic diffusion processes estimated from observations of first-hitting times: application to the leaky integrate-and-fire neuronal model. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[10]  Walter Senn,et al.  Minimal Models of Adapted Neuronal Response to In VivoLike Input Currents , 2004, Neural Computation.

[11]  Petr Lánský,et al.  Inference for the diffusion models of neuronal activity , 1983 .

[12]  Rune W. Berg,et al.  Balanced Inhibition and Excitation Drive Spike Activity in Spinal Half-Centers , 2007, Science.

[13]  Laura Sacerdote,et al.  On the comparison of Feller and Ornstein-Uhlenbeck models for neural activity , 1995, Biological Cybernetics.

[14]  Petr Lánský,et al.  The parameters of the stochastic leaky integrate-and-fire neuronal model , 2006, Journal of Computational Neuroscience.

[15]  Anthony N. Burkitt,et al.  A Review of the Integrate-and-fire Neuron Model: I. Homogeneous Synaptic Input , 2006, Biological Cybernetics.

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

[17]  Andrew T. A. Wood,et al.  Counting process intensity estimation by orthogonal wavelet methods , 2004 .

[18]  Romain Brette,et al.  Characterizing synaptic conductance fluctuations in cortical neurons and their influence on spike generation , 2007, Journal of Neuroscience Methods.

[19]  J. Hammersley,et al.  Diffusion Processes and Related Topics in Biology , 1977 .

[20]  P. Lánský,et al.  Diffusion approximation of the neuronal model with synaptic reversal potentials , 1987, Biological Cybernetics.

[21]  Wulfram Gerstner,et al.  Predicting spike timing of neocortical pyramidal neurons by simple threshold models , 2006, Journal of Computational Neuroscience.

[22]  M. J. Richardson,et al.  Firing-rate response of linear and nonlinear integrate-and-fire neurons to modulated current-based and conductance-based synaptic drive. , 2007, Physical review. E, Statistical, nonlinear, and soft matter physics.

[23]  Eero P. Simoncelli,et al.  Comparing integrate-and-fire models estimated using intracellular and extracellular data , 2005, Neurocomputing.

[24]  Wulfram Gerstner,et al.  Extracting non-linear integrate-and-fire models from experimental data using dynamic I–V curves , 2008, Biological Cybernetics.

[25]  Reinhard Höpfner,et al.  A stochastic model and a functional central limit theorem for information processing in large systems of neurons , 2006, Journal of mathematical biology.

[26]  L Sacerdote,et al.  Jump-diffusion processes as models for neuronal activity. , 1997, Bio Systems.

[27]  Reinhard Höpfner,et al.  On a set of data for the membrane potential in a neuron. , 2007, Mathematical biosciences.

[28]  Nicolas Brunel,et al.  Dynamics of the Instantaneous Firing Rate in Response to Changes in Input Statistics , 2005, Journal of Computational Neuroscience.

[29]  G. A. Robertson,et al.  Synaptic control of hindlimb motoneurones during three forms of the fictive scratch reflex in the turtle. , 1988, The Journal of physiology.

[30]  Jufang He,et al.  Effect of stimulation on the input parameters of stochastic leaky integrate-and-fire neuronal model , 2010, Journal of Physiology-Paris.

[31]  D. Florens-zmirou On estimating the diffusion coefficient from discrete observations , 1993, Journal of Applied Probability.

[32]  Petr Lánský,et al.  A review of the methods for signal estimation in stochastic diffusion leaky integrate-and-fire neuronal models , 2008, Biological Cybernetics.

[33]  J. Hounsgaard,et al.  Metabotropic Modulation of Motoneurons by Scratch-Like Spinal Network Activity , 2003, The Journal of Neuroscience.

[34]  Luigi M. Ricciardi,et al.  On the parameter estimation for diffusion models of single neuron's activities , 1995, Biological Cybernetics.

[35]  M. Carandini,et al.  Summation and division by neurons in primate visual cortex. , 1994, Science.

[36]  C. Koch,et al.  Multiplicative computation in a visual neuron sensitive to looming , 2002, Nature.

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

[38]  Andrea De Gaetano,et al.  Parameters of the Diffusion Leaky Integrate-and-Fire Neuronal Model for a Slowly Fluctuating Signal , 2008, Neural Computation.

[39]  Susanne Ditlevsen,et al.  Comparison of Statistical Methods for Estimation of the Input Parameters in the Ornstein‐Uhlenbeck Neuronal Model from First‐Passage Times Data , 2008 .

[40]  J. Hounsgaard,et al.  Periodic High-Conductance States in Spinal Neurons during Scratch-Like Network Activity in Adult Turtles , 2005, The Journal of Neuroscience.

[41]  Jean-Pascal Pfister,et al.  Optimal Spike-Timing-Dependent Plasticity for Precise Action Potential Firing in Supervised Learning , 2005, Neural Computation.

[42]  Ove Ditlevsen,et al.  Parameter estimation from observations of first-passage times of the Ornstein–Uhlenbeck process and the Feller process , 2008 .

[43]  Henry C. Tuckwell,et al.  Introduction to theoretical neurobiology , 1988 .

[44]  Ari Berkowitz,et al.  Spinal Interneurons That Are Selectively Activated during Fictive Flexion Reflex , 2007, The Journal of Neuroscience.

[45]  Susanne Ditlevsen,et al.  Synaptic inhibition and excitation estimated via the time constant of membrane potential fluctuations. , 2013, Journal of neurophysiology.

[46]  Eero P. Simoncelli,et al.  Maximum Likelihood Estimation of a Stochastic Integrate-and-Fire Neural Encoding Model , 2004, Neural Computation.

[47]  J. Barrett,et al.  Motoneuron dendrites: role in synaptic integration. , 1975, Federation proceedings.

[48]  A. Destexhe,et al.  Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. , 1999, Journal of neurophysiology.

[49]  Susanne Ditlevsen,et al.  Estimation of the input parameters in the Ornstein-Uhlenbeck neuronal model. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[50]  M. Carandini,et al.  Stimulus dependence of two-state fluctuations of membrane potential in cat visual cortex , 2000, Nature Neuroscience.

[51]  Wulfram Gerstner,et al.  Predicting neuronal activity with simple models of the threshold type: Adaptive Exponential Integrate-and-Fire model with two compartments , 2007, Neurocomputing.

[52]  D. Hansel,et al.  How Noise Contributes to Contrast Invariance of Orientation Tuning in Cat Visual Cortex , 2002, The Journal of Neuroscience.

[53]  Liam Paninski,et al.  Efficient estimation of detailed single-neuron models. , 2006, Journal of neurophysiology.

[54]  C. Koch,et al.  Synaptic Background Activity Influences Spatiotemporal Integration in Single Pyramidal Cells. , 1991, The Biological bulletin.

[55]  Finbarr O'Sullivan,et al.  Nonparametric Estimation in the Cox Model , 1993 .

[56]  P. Lánský,et al.  Estimating input parameters from intracellular recordings in the Feller neuronal model. , 2010, Physical review. E, Statistical, nonlinear, and soft matter physics.

[57]  Yutaka Sakai,et al.  The Ornstein-Uhlenbeck Process Does Not Reproduce Spiking Statistics of Neurons in Prefrontal Cortex , 1999, Neural Computation.

[58]  J. Hounsgaard,et al.  Intense Synaptic Activity Enhances Temporal Resolution in Spinal Motoneurons , 2008, PloS one.

[59]  D. Hansel,et al.  How Spike Generation Mechanisms Determine the Neuronal Response to Fluctuating Inputs , 2003, The Journal of Neuroscience.

[60]  Susanne Ditlevsen,et al.  Estimation of the input parameters in the Feller neuronal model. , 2006, Physical review. E, Statistical, nonlinear, and soft matter physics.

[61]  Satish Iyengar,et al.  Parameter estimation for a leaky integrate-and-fire neuronal model from ISI data , 2008, Journal of Computational Neuroscience.

[62]  Wulfram Gerstner,et al.  Generalized integrate-and-fire models of neuronal activity approximate spike trains of a detailed model to a high degree of accuracy. , 2004, Journal of neurophysiology.

[63]  Niels Keiding,et al.  Statistical Models Based on Counting Processes , 1993 .

[64]  Wulfram Gerstner,et al.  Spiking Neuron Models , 2002 .