On the mechanisms underlying the depolarization block in the spiking dynamics of CA1 pyramidal neurons

Under sustained input current of increasing strength neurons eventually stop firing, entering a depolarization block. This is a robust effect that is not usually explored in experiments or explicitly implemented or tested in models. However, the range of current strength needed for a depolarization block could be easily reached with a random background activity of only a few hundred excitatory synapses. Depolarization block may thus be an important property of neurons that should be better characterized in experiments and explicitly taken into account in models at all implementation scales. Here we analyze the spiking dynamics of CA1 pyramidal neuron models using the same set of ionic currents on both an accurate morphological reconstruction and on its reduction to a single-compartment. The results show the specific ion channel properties and kinetics that are needed to reproduce the experimental findings, and how their interplay can drastically modulate the neuronal dynamics and the input current range leading to a depolarization block. We suggest that this can be one of the rate-limiting mechanisms protecting a CA1 neuron from excessive spiking activity.

[1]  Karl Maramorosch,et al.  Rita Levi-Montalcini , 1989 .

[2]  Giorgio A Ascoli,et al.  Distinct classes of pyramidal cells exhibit mutually exclusive firing patterns in hippocampal area CA3b , 2008, Hippocampus.

[3]  T. Freund,et al.  Total number and distribution of inhibitory and excitatory synapses on hippocampal CA1 pyramidal cells , 2001, Neuroscience.

[4]  Gordon M Shepherd,et al.  Opinion: an integrated approach to classifying neuronal phenotypes. , 2005, Nature reviews. Neuroscience.

[5]  Nicholas T. Carnevale,et al.  The NEURON Simulation Environment , 1997, Neural Computation.

[6]  G. Shepherd,et al.  An integrated approach to classifying neuronal phenotypes , 2005, Nature Reviews Neuroscience.

[7]  Erin M. Schuman,et al.  Frontiers in Cellular Neuroscience Cellular Neuroscience , 2022 .

[8]  D. Johnston,et al.  K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons , 1997, Nature.

[9]  Michele Migliore,et al.  Role of an A-Type K+ Conductance in the Back-Propagation of Action Potentials in the Dendrites of Hippocampal Pyramidal Neurons , 1999, Journal of Computational Neuroscience.

[10]  G. Shepherd,et al.  Emerging rules for the distributions of active dendritic conductances , 2002, Nature Reviews Neuroscience.

[11]  Bartlett W. Mel,et al.  Pyramidal Neuron as Two-Layer Neural Network , 2003, Neuron.

[12]  Vivien A. Casagrande,et al.  Biophysics of Computation: Information Processing in Single Neurons , 1999 .

[13]  Jeffrey C Magee,et al.  Phosphorylation‐dependent differences in the activation properties of distal and proximal dendritic Na+ channels in rat CA1 hippocampal neurons , 2002, The Journal of physiology.

[14]  Qishao Lu,et al.  Control of firing patterns by two transient potassium currents: leading spike, latency, bistability , 2011, Journal of Computational Neuroscience.

[15]  W. Troy The bifurcation of periodic solutions in the Hodgkin-Huxley equations , 1978 .

[16]  M. Dichter,et al.  Cellular mechanisms of epilepsy: a status report. , 1987, Science.

[17]  Wei R. Chen,et al.  Dynamic Gating of Spike Propagation in the Mitral Cell Lateral Dendrites , 2002, Neuron.

[18]  M. Migliore Modeling the attenuation and failure of action potentials in the dendrites of hippocampal neurons. , 1996, Biophysical journal.

[19]  R. Traub,et al.  A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. , 1991, Journal of neurophysiology.

[20]  B. Hassard Bifurcation of periodic solutions of Hodgkin-Huxley model for the squid giant axon. , 1978, Journal of theoretical biology.

[21]  R. Traub,et al.  Cellular mechanism of neuronal synchronization in epilepsy. , 1982, Science.

[22]  Krasimira Tsaneva-Atanasova,et al.  A unified model of CA1/3 pyramidal cells: an investigation into excitability. , 2011, Progress in biophysics and molecular biology.

[23]  M. Nedergaard,et al.  Paired‐pulse modulation at individual GABAergic synapses in rat hippocampus , 2000, The Journal of physiology.

[24]  S. Hoffman,et al.  Funding for malaria genome sequencing , 1997, Nature.

[25]  N. Spruston,et al.  Activity-dependent action potential invasion and calcium influx into hippocampal CA1 dendrites. , 1995, Science.

[26]  Addolorata Marasco Scientific Computing with Mathematica: Mathematical Problems for Ordinary Differential Equations with Cdrom , 2001 .

[27]  E. Cavalheiro,et al.  Morphological and electrophysiological properties of pyramidal-like neurons in the stratum oriens of Cornu ammonis 1 and Cornu ammonis 2 area of Proechimys , 2011, Neuroscience.

[28]  D. Johnston,et al.  Downregulation of Transient K+ Channels in Dendrites of Hippocampal CA1 Pyramidal Neurons by Activation of PKA and PKC , 1998, The Journal of Neuroscience.

[29]  Enrico Cherubini,et al.  At Immature Mossy Fibers-CA3 Connections, Activation of Presynaptic GABAB Receptors by Endogenously Released GABA Contributes to Synapses Silencing , 2008, Front. Cell. Neurosci..

[30]  R Latorre,et al.  Gating kinetics of Ca2+-activated K+ channels from rat muscle incorporated into planar lipid bilayers. Evidence for two voltage- dependent Ca2+ binding reactions , 1983, The Journal of general physiology.

[31]  Wade Morishita,et al.  Generation of Silent Synapses by Acute In Vivo Expression of CaMKIV and CREB , 2005, Neuron.

[32]  John Rinzel,et al.  Intrinsic and network rhythmogenesis in a reduced traub model for CA3 neurons , 2004, Journal of Computational Neuroscience.

[33]  J. Magee,et al.  Distance-Dependent Increase in AMPA Receptor Number in the Dendrites of Adult Hippocampal CA1 Pyramidal Neurons , 2001, The Journal of Neuroscience.

[34]  Michael A. Arbib,et al.  The handbook of brain theory and neural networks , 1995, A Bradford book.

[35]  Henry Markram,et al.  Minimal Hodgkin–Huxley type models for different classes of cortical and thalamic neurons , 2008, Biological Cybernetics.

[36]  C. Colbert,et al.  Ion channel properties underlying axonal action potential initiation in pyramidal neurons , 2002, Nature Neuroscience.

[37]  J. Magee Dendritic Hyperpolarization-Activated Currents Modify the Integrative Properties of Hippocampal CA1 Pyramidal Neurons , 1998, The Journal of Neuroscience.

[38]  Bartlett W. Mel,et al.  Arithmetic of Subthreshold Synaptic Summation in a Model CA1 Pyramidal Cell , 2003, Neuron.

[39]  S. Remy,et al.  Plasticity of voltage-gated ion channels in pyramidal cell dendrites , 2010, Current Opinion in Neurobiology.

[40]  D. McCormick,et al.  On the cellular and network bases of epileptic seizures. , 2001, Annual review of physiology.

[41]  Christof Koch,et al.  Biophysics of Computation: Information Processing in Single Neurons (Computational Neuroscience Series) , 1998 .

[42]  M. Migliore,et al.  Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons , 2008, Proceedings of the National Academy of Sciences.

[43]  David Golomb,et al.  Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study. , 2006, Journal of neurophysiology.

[44]  Antonio Romano Scientific Computing with Mathematica®: Mathematical Problems for Ordinary Differential Equations , 2013 .

[45]  Szabolcs Káli,et al.  Differences in subthreshold resonance of hippocampal pyramidal cells and interneurons: the role of h-current and passive membrane characteristics , 2010, The Journal of physiology.

[46]  Giorgio A Ascoli,et al.  Statistical determinants of dendritic morphology in hippocampal pyramidal neurons: A hidden Markov model , 2005, Hippocampus.

[47]  G F Ayala,et al.  Genesis of epileptic interictal spikes. New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysms. , 1973, Brain research.