Modeling the Electrophysiology of Suprachiasmatic Nucleus Neurons

Neurons in the SCN act as the central circadian (~24-h) pacemaker in mammals. Using measurements of the ionic currents in SCN neurons, the authors fit a Hodgkin-Huxley-type model that accurately reproduces slow (~2-8 Hz) neural firing as well as the contributions of ionic currents during an action potential. When inputs of other SCN neurons are considered, the model accurately predicts the fractal nature of firing rates and the appearance of random bursting. In agreement with experimental data, the molecular clock within these neurons modulates the firing rate through small changes in the concentration of internal calcium, calcium channels, or potassium channels. Predictions are made on how signals from other neurons can start, stop, speed up, or slow down firing. Only a slow sodium inactivation variable and voltage do not reach equilibrium during the interval between action potentials, and based on this finding, a reduced model is formulated.

[1]  S. Honma,et al.  Synchronization of circadian firing rhythms in cultured rat suprachiasmatic neurons , 2000 .

[2]  D. Paydarfar,et al.  Sporadic apnea: paradoxical transformation to eupnea by perturbations that inhibit inspiration. , 1997, Medical hypotheses.

[3]  F. Dudek,et al.  Mechanism of irregular firing of suprachiasmatic nucleus neurons in rat hypothalamic slices. , 2004, Journal of neurophysiology.

[4]  W J Schwartz,et al.  Antiphase oscillation of the left and right suprachiasmatic nuclei. , 2000, Science.

[5]  Daniel B. Forger,et al.  Stochastic simulation of the mammalian circadian clock. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[6]  J. Meijer,et al.  Light Responsiveness of the Suprachiasmatic Nucleus: Long-Term Multiunit and Single-Unit Recordings in Freely Moving Rats , 1998, The Journal of Neuroscience.

[7]  Daniel B. Forger,et al.  An opposite role for tau in circadian rhythms revealed by mathematical modeling. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Nicholas C. Foley,et al.  Gates and Oscillators: A Network Model of the Brain Clock , 2003, Journal of biological rhythms.

[9]  A. Goldbeter,et al.  Toward a detailed computational model for the mammalian circadian clock , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[10]  G. Ermentrout,et al.  Analysis of neural excitability and oscillations , 1989 .

[11]  S. Yamaguchi,et al.  Synchronization of Cellular Clocks in the Suprachiasmatic Nucleus , 2003, Science.

[12]  J. Clark,et al.  A model of the action potential and underlying membrane currents in a rabbit atrial cell. , 1996, The American journal of physiology.

[13]  勇一 作村,et al.  Biophysics of Computation , 2001 .

[14]  Jaeseung Jeong,et al.  Fractal Stochastic Modeling of Spiking Activity in Suprachiasmatic Nucleus Neurons , 2005, Journal of Computational Neuroscience.

[15]  C. Pennartz,et al.  Cellular mechanisms underlying spontaneous firing in rat suprachiasmatic nucleus: involvement of a slowly inactivating component of sodium current. , 1997, Journal of neurophysiology.

[16]  W. Rietveld,et al.  Ionic currents in cultured rat suprachiasmatic neurons , 1995, Neuroscience.

[17]  A. Hodgkin,et al.  A quantitative description of membrane current and its application to conduction and excitation in nerve , 1990 .

[18]  A. Miyawaki,et al.  Circadian Dynamics of Cytosolic and Nuclear Ca2+ in Single Suprachiasmatic Nucleus Neurons , 2003, Neuron.

[19]  R E Kronauer,et al.  A Simpler Model of the Human Circadian Pacemaker , 1999, Journal of biological rhythms.

[20]  Mariska J Vansteensel,et al.  Sleep states alter activity of suprachiasmatic nucleus neurons , 2003, Nature Neuroscience.

[21]  Joseph S. Takahashi,et al.  Chimera Analysis of the Clock Mutation in Mice Shows that Complex Cellular Integration Determines Circadian Behavior , 2001, Cell.

[22]  J. Clark,et al.  Mathematical model of an adult human atrial cell: the role of K+ currents in repolarization. , 1998, Circulation research.

[23]  F. Dudek,et al.  Noise of the slowly inactivating Na current in suprachiasmatic nucleus neurons , 2005, Neuroreport.

[24]  C. Allen,et al.  Potential pathways for intercellular communication within the calbindin subnucleus of the hamster suprachiasmatic nucleus , 2004, Neuroscience.

[25]  Giulio Tononi,et al.  Modeling sleep and wakefulness in the thalamocortical system. , 2005, Journal of neurophysiology.

[26]  Daniel B. Forger,et al.  A detailed predictive model of the mammalian circadian clock , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  William J Schwartz,et al.  Forced Desynchronization of Dual Circadian Oscillators within the Rat Suprachiasmatic Nucleus , 2004, Current Biology.

[28]  Richard E. Kronauer,et al.  Quantifying Human Circadian Pacemaker Response to Brief, Extended, and Repeated Light Stimuli over the Phototopic Range , 1999, Journal of biological rhythms.

[29]  D. A. Baxter,et al.  Computational model of the serotonergic modulation of sensory neurons in Aplysia. , 1999, Journal of neurophysiology.

[30]  F. Dudek,et al.  Persistent calcium current in rat suprachiasmatic nucleus neurons , 2006, Neuroscience.

[31]  Paul E. Brown,et al.  Extension of a genetic network model by iterative experimentation and mathematical analysis , 2005, Molecular systems biology.

[32]  J. D. Miller,et al.  Isoperiodic neuronal activity in suprachiasmatic nucleus of the rat. , 1992, The American journal of physiology.

[33]  Johanna H. Meijer,et al.  Heterogeneity of rhythmic suprachiasmatic nucleus neurons: Implications for circadian waveform and photoperiodic encoding , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  A. Winfree The geometry of biological time , 1991 .

[35]  E. Marani,et al.  Spontaneous and stimulated firing in cultured rat suprachiasmatic neurons , 1992, Brain Research.

[36]  F. Dudek,et al.  A rapidly activating type of outward rectifier K+ current and A‐current in rat suprachiasmatic nucleus neurones. , 1995, The Journal of physiology.

[37]  F. Dudek,et al.  Riluzole-sensitive slowly inactivating sodium current in rat suprachiasmatic nucleus neurons. , 2004, Journal of neurophysiology.

[38]  B. Bean,et al.  Mechanism of Spontaneous Firing in Dorsomedial Suprachiasmatic Nucleus Neurons , 2004, The Journal of Neuroscience.

[39]  James P. Keener,et al.  Mathematical physiology , 1998 .

[40]  P Achermann,et al.  Modeling Circadian Rhythm Generation in the Suprachiasmatic Nucleus with Locally Coupled Self-Sustained Oscillators: Phase Shifts and Phase Response Curves , 1999, Journal of biological rhythms.

[41]  Diane Lipscombe,et al.  L-type calcium channels: the low down. , 2004, Journal of neurophysiology.

[42]  David Paydarfar,et al.  Noisy inputs and the induction of on-off switching behavior in a neuronal pacemaker. , 2006, Journal of neurophysiology.

[43]  C. Colwell,et al.  Fast delayed rectifier potassium current is required for circadian neural activity , 2005, Nature Neuroscience.

[44]  Douglas G. McMahon,et al.  Daily rhythmicity of large-conductance Ca2+-activated K+ currents in suprachiasmatic nucleus neurons , 2006, Brain Research.

[45]  R. Cloues,et al.  Afterhyperpolarization Regulates Firing Rate in Neurons of the Suprachiasmatic Nucleus , 2003, The Journal of Neuroscience.

[46]  C. Allen,et al.  GABAergic synapses of the suprachiasmatic nucleus exhibit a diurnal rhythm of short‐term synaptic plasticity , 2004, The European journal of neuroscience.

[47]  H. Oster The genetic basis of circadian behavior , 2006, Genes, brain, and behavior.

[48]  C. Allen,et al.  Characterization of an apamin-sensitive potassium current in suprachiasmatic nucleus neurons , 2003, Neuroscience.

[49]  C. Pennartz,et al.  Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock , 2002, Nature.