Resurgent Na+ Current Offers Noise Modulation in Bursting Neurons

Neurons utilize bursts of action potentials as an efficient and reliable way to encode information. It is likely that the intrinsic membrane properties of neurons involved in burst generation may also participate in preserving its temporal features. Here we examined the contribution of the persistent and resurgent components of voltage-gated Na+ currents in modulating the burst discharge in sensory neurons. Using mathematical modeling, theory and dynamic-clamp electrophysiology, we show that, distinct from the persistent Na+ component which is important for membrane resonance and burst generation, the resurgent Na+ can help stabilize burst timing features including the duration and intervals. Moreover, such a physiological role for the resurgent Na+ offered noise tolerance and preserved the regularity of burst patterns. Model analysis further predicted a negative feedback loop between the persistent and resurgent gating variables which mediate such gain in burst stability. These results highlight a novel role for the voltage-gated resurgent Na+ component in moderating the entropy of burst-encoded neural information.

[1]  W. Catterall,et al.  From Ionic Currents to Molecular Mechanisms The Structure and Function of Voltage-Gated Sodium Channels , 2000, Neuron.

[2]  I. Raman,et al.  Properties of Sodium Currents and Action Potential Firing in Isolated Cerebellar Purkinje Neurons , 1999, Annals of the New York Academy of Sciences.

[3]  Thierry Bal,et al.  Corticothalamic Synaptic Noise as a Mechanism for Selective Attention in Thalamic Neurons , 2015, Front. Neural Circuits.

[4]  E. Izhikevich,et al.  Persistent sodium currents in mesencephalic v neurons participate in burst generation and control of membrane excitability. , 2005, Journal of neurophysiology.

[5]  S. I. Levin,et al.  Impaired motor function in mice with cell-specific knockout of sodium channel Scn8a (NaV1.6) in cerebellar purkinje neurons and granule cells. , 2006, Journal of neurophysiology.

[6]  F. Mechler,et al.  Interspike Intervals, Receptive Fields, and Information Encoding in Primary Visual Cortex , 2000, The Journal of Neuroscience.

[7]  Nathan W. Gouwens,et al.  The Contribution of Resurgent Sodium Current to High-Frequency Firing in Purkinje Neurons: An Experimental and Modeling Study , 2003, The Journal of Neuroscience.

[8]  I. Raman,et al.  Resurgent Sodium Current and Action Potential Formation in Dissociated Cerebellar Purkinje Neurons , 1997, The Journal of Neuroscience.

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

[10]  Y Zheng,et al.  Proportional spike-timing precision and firing reliability underlie efficient temporal processing of periodicity and envelope shape cues. , 2013, Journal of neurophysiology.

[11]  Frank C. Hoppensteadt,et al.  Bursts as a unit of neural information: selective communication via resonance , 2003, Trends in Neurosciences.

[12]  I. Raman,et al.  Open-Channel Block by the Cytoplasmic Tail of Sodium Channel β4 as a Mechanism for Resurgent Sodium Current , 2005, Neuron.

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

[14]  N. Slater,et al.  Resurgent Na currents in four classes of neurons of the cerebellum. , 2004, Journal of neurophysiology.

[15]  Egidio D'Angelo,et al.  Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study , 2006, The Journal of physiology.

[16]  Paolo Massobrio,et al.  A single Markov-type kinetic model accounting for the macroscopic currents of all human voltage-gated sodium channel isoforms , 2017, PLoS Comput. Biol..

[17]  M. Meisler,et al.  Aberrant Sodium Channel Currents and Hyperexcitability of Medial Entorhinal Cortex Neurons in a Mouse Model of SCN8A Encephalopathy , 2017, The Journal of Neuroscience.

[18]  Claude E. Shannon,et al.  A mathematical theory of communication , 1948, MOCO.

[19]  S. H. Chandler,et al.  Sodium currents in mesencephalic trigeminal neurons from Nav1.6 null mice. , 2007, Journal of neurophysiology.

[20]  P. Ruben,et al.  Slow inactivation in voltage-gated sodium channels , 2007, Cell Biochemistry and Biophysics.

[21]  A. Faisal,et al.  Noise in the nervous system , 2008, Nature Reviews Neuroscience.

[22]  Y. Yarom,et al.  Resonance, oscillation and the intrinsic frequency preferences of neurons , 2000, Trends in Neurosciences.

[23]  B. Bean,et al.  Subthreshold Sodium Current from Rapidly Inactivating Sodium Channels Drives Spontaneous Firing of Tuberomammillary Neurons , 2002, Neuron.

[24]  Lorin S Milescu,et al.  Kinetic Properties and Functional Dynamics of Sodium Channels during Repetitive Spiking in a Slow Pacemaker Neuron , 2010, The Journal of Neuroscience.

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

[26]  D. Jagger,et al.  Identification of Persistent and Resurgent Sodium Currents in Spiral Ganglion Neurons Cultured from the Mouse Cochlea , 2017, eNeuro.

[27]  Lorin S Milescu,et al.  Real-time kinetic modeling of voltage-gated ion channels using dynamic clamp. , 2008, Biophysical journal.

[28]  Nicholas W. Plummer,et al.  Functional Analysis of the Mouse Scn8a Sodium Channel , 1998, The Journal of Neuroscience.

[29]  E Marder,et al.  Encoding of muscle movement on two time scales by a sensory neuron that switches between spiking and bursting modes. , 1999, Journal of neurophysiology.

[30]  M. Devor,et al.  Burst discharge in primary sensory neurons: triggered by subthreshold oscillations, maintained by depolarizing afterpotentials. , 2002, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  S. H. Chandler,et al.  Membrane Resonance and Subthreshold Membrane Oscillations in Mesencephalic V Neurons: Participants in Burst Generation , 2001, The Journal of Neuroscience.

[32]  A Garfinkel,et al.  Evidence for a novel bursting mechanism in rodent trigeminal neurons. , 1998, Biophysical journal.

[33]  T. Sejnowski,et al.  Regulation of spike timing in visual cortical circuits , 2008, Nature Reviews Neuroscience.

[34]  I. Raman,et al.  Inactivation and recovery of sodium currents in cerebellar Purkinje neurons: evidence for two mechanisms. , 2001, Biophysical journal.

[35]  James O. Jackson,et al.  Human voltage-gated sodium channel mutations that cause inherited neuronal and muscle channelopathies increase resurgent sodium currents. , 2010, The Journal of clinical investigation.

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

[37]  William Bialek,et al.  Reading a Neural Code , 1991, NIPS.

[38]  I. Raman,et al.  Altered Subthreshold Sodium Currents and Disrupted Firing Patterns in Purkinje Neurons of Scn8a Mutant Mice , 1997, Neuron.

[39]  Robert J Butera,et al.  Persistent sodium current, membrane properties and bursting behavior of pre-bötzinger complex inspiratory neurons in vitro. , 2002, Journal of neurophysiology.

[40]  Zayd M. Khaliq,et al.  Relative Contributions of Axonal and Somatic Na Channels to Action Potential Initiation in Cerebellar Purkinje Neurons , 2006, The Journal of Neuroscience.

[41]  R. Llinás,et al.  Subthreshold Na+-dependent theta-like rhythmicity in stellate cells of entorhinal cortex layer II , 1989, Nature.

[42]  Marco A Navarro,et al.  Kinetic properties of persistent Na+ current orchestrate oscillatory bursting in respiratory neurons , 2018, The Journal of general physiology.

[43]  J. Lisman.  Bursts as a unit of neural information: making unreliable synapses reliable , 1997, Trends in Neurosciences.

[44]  M. Kogo,et al.  Development of resurgent and persistent sodium currents in mesencephalic trigeminal neurons , 2018, Journal of neuroscience research.

[45]  J. P. Lund,et al.  Synaptic inputs to trigeminal primary afferent neurons cause firing and modulate intrinsic oscillatory activity. , 2004, Journal of neurophysiology.

[46]  H. von Gersdorff,et al.  Presynaptic Resurgent Na+ Currents Sculpt the Action Potential Waveform and Increase Firing Reliability at a CNS Nerve Terminal , 2010, The Journal of Neuroscience.

[47]  S. H. Chandler,et al.  Participation of Sodium Currents in Burst Generation and Control of Membrane Excitability in Mesencephalic Trigeminal Neurons , 2006, The Journal of Neuroscience.

[48]  V. Han,et al.  Membrane current-based mechanisms for excitability transitions in neurons of the rat mesencephalic trigeminal nuclei , 2009, Neuroscience.

[49]  David J. Christini,et al.  Real-time Experiment Interface for biological control applications , 2010, 2010 Annual International Conference of the IEEE Engineering in Medicine and Biology.

[50]  Joseph L. Ransdell,et al.  Loss of Navβ4-Mediated Regulation of Sodium Currents in Adult Purkinje Neurons Disrupts Firing and Impairs Motor Coordination and Balance. , 2017, Cell reports.

[51]  P. Schwindt,et al.  Amplification of synaptic current by persistent sodium conductance in apical dendrite of neocortical neurons. , 1995, Journal of neurophysiology.

[52]  S. H. Chandler,et al.  Physiological and theoretical analysis of K+ currents controlling discharge in neonatal rat mesencephalic trigeminal neurons. , 1997, Journal of neurophysiology.

[53]  Eve Marder,et al.  The dynamic clamp comes of age , 2004, Trends in Neurosciences.

[54]  L. Pinneo.  On noise in the nervous system. , 1966, Psychological review.