Modeling the Modulation of Neuronal Bursting: A Singularity Theory Approach

Exploiting the specific structure of neuron conductance-based models, the paper investigates the mathematical modeling of neuronal bursting modulation. The proposed approach combines singularity theory and geometric singular perturbations to capture the geometry of multiple time-scale attractors in the neighborhood of high-codimension singularities. We detect a three--time-scale bursting attractor in the universal unfolding of the winged cusp singularity and discuss the physiological relevance of the bifurcation and unfolding parameters in determining a physiological modulation of bursting. The results suggest generality and simplicity in the organizing role of the winged cusp singularity for the global dynamics of conductance-based models.

[1]  David Terman,et al.  Chaotic spikes arising from a model of bursting in excitable membranes , 1991 .

[2]  Rodolphe Sepulchre,et al.  A Novel Phase Portrait for Neuronal Excitability , 2012, PLoS ONE.

[3]  Martin Golubitsky,et al.  An unfolding theory approach to bursting in fast–slow systems , 2001 .

[4]  J. Rinzel Excitation dynamics: insights from simplified membrane models. , 1985, Federation proceedings.

[5]  J. Rinzel,et al.  Dissection of a model for neuronal parabolic bursting , 1987, Journal of mathematical biology.

[6]  Eugene M. Izhikevich,et al.  Dynamical Systems in Neuroscience: The Geometry of Excitability and Bursting , 2006 .

[7]  S. Sherman Tonic and burst firing: dual modes of thalamocortical relay , 2001, Trends in Neurosciences.

[8]  J. Grasman Asymptotic Methods for Relaxation Oscillations and Applications , 1987 .

[9]  R. Bertram,et al.  Topological and phenomenological classification of bursting oscillations. , 1995, Bulletin of mathematical biology.

[10]  Fabrizio Gabbiani,et al.  Burst firing in sensory systems , 2004, Nature Reviews Neuroscience.

[11]  S. Chow,et al.  Normal Forms and Bifurcation of Planar Vector Fields , 1994 .

[12]  M. Golubitsky,et al.  Singularities and Groups in Bifurcation Theory: Volume I , 1984 .

[13]  S. Chow,et al.  Homoclinic bifurcation at resonant eigenvalues , 1990 .

[14]  Eugene M. Izhikevich,et al.  Neural excitability, Spiking and bursting , 2000, Int. J. Bifurc. Chaos.

[15]  Andrey Shilnikov,et al.  Methods of the Qualitative Theory for the Hindmarsh-rose Model: a Case Study - a Tutorial , 2008, Int. J. Bifurc. Chaos.

[16]  Eve Marder,et al.  Alternative to hand-tuning conductance-based models: construction and analysis of databases of model neurons. , 2003, Journal of neurophysiology.

[17]  Rodolphe Sepulchre,et al.  An Organizing Center in a Planar Model of Neuronal Excitability , 2012, SIAM J. Appl. Dyn. Syst..

[18]  John Rinzel,et al.  A Formal Classification of Bursting Mechanisms in Excitable Systems , 1987 .

[19]  B Bioulac,et al.  Subthalamic Nucleus Neurons Switch from Single-Spike Activity to Burst-Firing Mode , 1999, The Journal of Neuroscience.

[20]  John P. Horn,et al.  Cav1.3 Channel Voltage Dependence, Not Ca2+ Selectivity, Drives Pacemaker Activity and Amplifies Bursts in Nigral Dopamine Neurons , 2009, The Journal of Neuroscience.

[21]  Jan-Marino Ramirez,et al.  Norepinephrine differentially modulates different types of respiratory pacemaker and nonpacemaker neurons. , 2006, Journal of neurophysiology.

[22]  Ralf D Wimmer,et al.  The CaV3.3 calcium channel is the major sleep spindle pacemaker in thalamus , 2011, Proceedings of the National Academy of Sciences.

[23]  J Rinzel,et al.  Current clamp and modeling studies of low-threshold calcium spikes in cells of the cat's lateral geniculate nucleus. , 1999, Journal of neurophysiology.

[24]  Christopher Jones,et al.  Geometric singular perturbation theory , 1995 .

[25]  Rodolphe Sepulchre,et al.  A Balance Equation Determines a Switch in Neuronal Excitability , 2012, PLoS Comput. Biol..

[26]  N. K. Rozov,et al.  Differential Equations with Small Parameters and Relaxation Oscillations , 1980 .

[27]  Peter Szmolyan,et al.  Extending Geometric Singular Perturbation Theory to Nonhyperbolic Points - Fold and Canard Points in Two Dimensions , 2001, SIAM J. Math. Anal..

[28]  M. Krupa,et al.  Relaxation Oscillation and Canard Explosion , 2001 .

[29]  Neil Fenichel Geometric singular perturbation theory for ordinary differential equations , 1979 .

[30]  R. FitzHugh Impulses and Physiological States in Theoretical Models of Nerve Membrane. , 1961, Biophysical journal.

[31]  E. Marder,et al.  A Model Neuron with Activity-Dependent Conductances Regulated by Multiple Calcium Sensors , 1998, The Journal of Neuroscience.

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

[33]  Peter Szmolyan,et al.  Extending slow manifolds near transcritical and pitchfork singularities , 2001 .

[34]  M. Golubitsky,et al.  Singularities and groups in bifurcation theory , 1985 .

[35]  J. Rubin,et al.  Effects of noise on elliptic bursters , 2004 .

[36]  D. James Surmeier,et al.  Robust Pacemaking in Substantia Nigra Dopaminergic Neurons , 2009, The Journal of Neuroscience.

[37]  J. Hindmarsh,et al.  A model of neuronal bursting using three coupled first order differential equations , 1984, Proceedings of the Royal Society of London. Series B. Biological Sciences.