Direct Current Stimulation Alters Neuronal Input/Output Function

BACKGROUND Direct current stimulation (DCS) affects both neuronal firing rate and synaptic efficacy. The neuronal input/output (I/O) function determines the likelihood that a neuron elicits an action potential in response to synaptic input of a given strength. Changes of the neuronal I/O function by DCS may underlie previous observations in animal models and human testing, yet have not been directly assessed. OBJECTIVE Test if the neuronal input/output function is affected by DCS METHODS: Using rat hippocampal brain slices and computational modeling, we provide evidence for how DCS modulates the neuronal I/O function. RESULTS We show for the first time that DCS modulates the likelihood of neuronal firing for a given and fixed synaptic input. Opposing polarization of soma and dendrite may have a synergistic effect for anodal stimulation, increasing the driving force of synaptic activity while simultaneously increasing spiking probability at the soma. For cathodal stimulation, however, the opposing effects tend to cancel. This results in an asymmetry in the strength of the effects of stimulation for opposite polarities. CONCLUSIONS Our results may explain the asymmetries observed in acute and long term effects of transcranial direct current stimulation.

[1]  Clay Armstrong,et al.  Synaptically triggered action potentials in dendrites , 1993, Neuron.

[2]  M. Nitsche,et al.  Facilitation of Implicit Motor Learning by Weak Transcranial Direct Current Stimulation of the Primary Motor Cortex in the Human , 2003, Journal of Cognitive Neuroscience.

[3]  L. Bindman,et al.  Long-lasting Changes in the Level of the Electrical Activity of the Cerebral Cortex produced by Polarizing Currents , 1962, Nature.

[4]  Terrence J. Sejnowski,et al.  An Efficient Method for Computing Synaptic Conductances Based on a Kinetic Model of Receptor Binding , 1994, Neural Computation.

[5]  Andrea Hasenstaub,et al.  Barrages of Synaptic Activity Control the Gain and Sensitivity of Cortical Neurons , 2003, The Journal of Neuroscience.

[6]  C. Nicholson,et al.  Effects of electric fields on transmembrane potential and excitability of turtle cerebellar Purkinje cells in vitro. , 1988, The Journal of physiology.

[7]  B. Nolan Boosting slow oscillations during sleep potentiates memory , 2008 .

[8]  W. Gerstner,et al.  Connectivity reflects coding: a model of voltage-based STDP with homeostasis , 2010, Nature Neuroscience.

[9]  M. Nitsche,et al.  Pharmacological Modulation of Cortical Excitability Shifts Induced by Transcranial Direct Current Stimulation in Humans , 2003, The Journal of physiology.

[10]  H. Adesnik,et al.  Input normalization by global feedforward inhibition expands cortical dynamic range , 2009, Nature Neuroscience.

[11]  J. Deans,et al.  Sensitivity of coherent oscillations in rat hippocampus to AC electric fields , 2007, The Journal of physiology.

[12]  T J Sejnowski,et al.  Cellular and network models for intrathalamic augmenting responses during 10-Hz stimulation. , 1998, Journal of neurophysiology.

[13]  H. Spitzer,et al.  Increased attention enhances both behavioral and neuronal performance. , 1988, Science.

[14]  M. Nitsche,et al.  Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence. , 2004, Investigative ophthalmology & visual science.

[15]  L. Cohen,et al.  Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. , 2005, Brain : a journal of neurology.

[16]  P. Schwindt,et al.  Modal gating of Na+ channels as a mechanism of persistent Na+ current in pyramidal neurons from rat and cat sensorimotor cortex , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  D. Prince,et al.  Electrophysiology of isolated hippocampal pyramidal dendrites , 1982, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  Tomaso Poggio,et al.  Fast Readout of Object Identity from Macaque Inferior Temporal Cortex , 2005, Science.

[19]  R. Desimone,et al.  Attention Increases Sensitivity of V4 Neurons , 2000, Neuron.

[20]  Sergio P. Rigonatti,et al.  Transient tinnitus suppression induced by repetitive transcranial magnetic stimulation and transcranial direct current stimulation , 2006, European journal of neurology.

[21]  Dean V. Buonomano,et al.  Timing and Balance of Inhibition Enhance the Effect of Long-Term Potentiation on Cell Firing , 2004, The Journal of Neuroscience.

[22]  D. McCormick,et al.  Endogenous Electric Fields May Guide Neocortical Network Activity , 2010, Neuron.

[23]  L. Merabet,et al.  Clinical research with transcranial direct current stimulation (tDCS): Challenges and future directions , 2012, Brain Stimulation.

[24]  I. Gartside,et al.  Mechanisms of Sustained Increases of Firing Rate of Neurones in the Rat Cerebral Cortex after Polarization: Role of Protein Synthesis , 1968, Nature.

[25]  R. W. Turner,et al.  Apical dendritic depolarizations and field interactions evoked by stimulation of afferent inputs to rat hippocampal ca1 pyramidal cells , 1991, Neuroscience.

[26]  Ethan R. Buch,et al.  Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation , 2009, Proceedings of the National Academy of Sciences.

[27]  A. Gardner-Medwin,et al.  Analysis of potassium dynamics in mammalian brain tissue. , 1983, The Journal of physiology.

[28]  Jacek Dmochowski,et al.  The “Quasi-Uniform” Assumption in Animal and Computational Models of Non-Invasive Electrical Stimulation , 2013, Brain Stimulation.

[29]  M. Nitsche,et al.  Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans , 2001, Neurology.

[30]  B. Sakmann,et al.  Active propagation of somatic action potentials into neocortical pyramidal cell dendrites , 1994, Nature.

[31]  M. Scanziani,et al.  Enforcement of Temporal Fidelity in Pyramidal Cells by Somatic Feed-Forward Inhibition , 2001, Science.

[32]  T. Bliss,et al.  Unit analysis of hippocampal population spikes , 2004, Experimental Brain Research.

[33]  Carrie J. McAdams,et al.  Effects of Attention on Orientation-Tuning Functions of Single Neurons in Macaque Cortical Area V4 , 1999, The Journal of Neuroscience.

[34]  Lucas C. Parra,et al.  Transcranial Slow Oscillation Stimulation During Sleep Enhances Memory Consolidation in Rats , 2014, Brain Stimulation.

[35]  Lucas C Parra,et al.  Lasting modulation of in vitro oscillatory activity with weak direct current stimulation. , 2015, Journal of neurophysiology.

[36]  M. Nitsche,et al.  Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation , 2000, The Journal of physiology.

[37]  J. Jefferys,et al.  Influence of electric fields on the excitability of granule cells in guinea‐pig hippocampal slices. , 1981, The Journal of physiology.

[38]  R Andy McKinley,et al.  Acceleration of image analyst training with transcranial direct current stimulation. , 2013, Behavioral neuroscience.

[39]  D. Reato,et al.  Gyri-precise head model of transcranial direct current stimulation: Improved spatial focality using a ring electrode versus conventional rectangular pad , 2009, Brain Stimulation.

[40]  Nace L. Golding,et al.  Dendritic Sodium Spikes Are Variable Triggers of Axonal Action Potentials in Hippocampal CA1 Pyramidal Neurons , 1998, Neuron.

[41]  R Llinás,et al.  Kinetic and stochastic properties of a persistent sodium current in mature guinea pig cerebellar Purkinje cells. , 1998, Journal of neurophysiology.

[42]  T. Sejnowski,et al.  A model of spike initiation in neocortical pyramidal neurons , 1995, Neuron.

[43]  B. Rockstroh,et al.  The influence of low-level transcortical DC-currents on response speed in humans. , 1981, The International journal of neuroscience.

[44]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[45]  L. Parra,et al.  Low-Intensity Electrical Stimulation Affects Network Dynamics by Modulating Population Rate and Spike Timing , 2010, The Journal of Neuroscience.

[46]  B. Sakmann,et al.  Cortex Is Driven by Weak but Synchronously Active Thalamocortical Synapses , 2006, Science.

[47]  J. Barker,et al.  The site for initiation of action potential discharge over the somatodendritic axis of rat hippocampal CA1 pyramidal neurons , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  V. Di Lazzaro,et al.  Modulation of LTP at rat hippocampal CA3-CA1 synapses by direct current stimulation. , 2012, Journal of neurophysiology.

[49]  Yuzhuo Su,et al.  Spike Timing Amplifies the Effect of Electric Fields on Neurons: Implications for Endogenous Field Effects , 2007, The Journal of Neuroscience.

[50]  D. Prince,et al.  Sodium channels in dendrites of rat cortical pyramidal neurons. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

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

[52]  J. Delgado-García,et al.  Transcranial direct-current stimulation modulates synaptic mechanisms involved in associative learning in behaving rabbits , 2012, Proceedings of the National Academy of Sciences.

[53]  S. Brandt,et al.  Transcranial direct current stimulation affects visual perception measured by threshold perimetry , 2010, Experimental Brain Research.

[54]  Heidi Johansen-Berg,et al.  Polarity-specific effects of motor transcranial direct current stimulation on fMRI resting state networks☆ , 2014, NeuroImage.

[55]  E. Jankowska,et al.  Presynaptic actions of transcranial and local direct current stimulation in the red nucleus , 2014, The Journal of physiology.

[56]  Á. Pascual-Leone,et al.  Contribution of axonal orientation to pathway-dependent modulation of excitatory transmission by direct current stimulation in isolated rat hippocampus. , 2012, Journal of neurophysiology.

[57]  D. Purpura,et al.  INTRACELLULAR ACTIVITIES AND EVOKED POTENTIAL CHANGES DURING POLARIZATION OF MOTOR CORTEX. , 1965, Journal of neurophysiology.

[58]  C. Stinear,et al.  Transcranial Direct Current Stimulation Intensity and Duration Effects on Tinnitus Suppression , 2013, Neurorehabilitation and neural repair.

[59]  D. Tank,et al.  Dendritic Integration in Mammalian Neurons, a Century after Cajal , 1996, Neuron.

[60]  Bin Deng,et al.  Exploring how extracellular electric field modulates neuron activity through dynamical analysis of a two-compartment neuron model , 2013, Journal of Computational Neuroscience.

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

[62]  C. Morris,et al.  Voltage oscillations in the barnacle giant muscle fiber. , 1981, Biophysical journal.

[63]  I. Timofeev,et al.  Interneuron‐mediated inhibition synchronizes neuronal activity during slow oscillation , 2012, The Journal of physiology.

[64]  Bruce J. Gluckman,et al.  A Model of the Effects of Applied Electric Fields on Neuronal Synchronization , 2005, Journal of Computational Neuroscience.

[65]  J. Jefferys,et al.  Effects of uniform extracellular DC electric fields on excitability in rat hippocampal slices in vitro , 2004, The Journal of physiology.

[66]  M. Gutnick,et al.  Persistent Sodium Current in Layer 5 Neocortical Neurons Is Primarily Generated in the Proximal Axon , 2006, The Journal of Neuroscience.

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

[68]  Christopher M. Lee,et al.  Heterosynaptic Plasticity Prevents Runaway Synaptic Dynamics , 2013, The Journal of Neuroscience.

[69]  Sadatoshi Tsuji,et al.  Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans , 2004, Clinical Neurophysiology.

[70]  J. Movshon,et al.  Linearity and Normalization in Simple Cells of the Macaque Primary Visual Cortex , 1997, The Journal of Neuroscience.

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

[72]  H. Hirase,et al.  Calcium imaging reveals glial involvement in transcranial direct current stimulation-induced plasticity in mouse brain , 2016, Nature Communications.

[73]  S. Laughlin A Simple Coding Procedure Enhances a Neuron's Information Capacity , 1981, Zeitschrift fur Naturforschung. Section C, Biosciences.

[74]  C A Terzuolo,et al.  MEASUREMENT OF IMPOSED VOLTAGE GRADIENT ADEQUATE TO MODULATE NEURONAL FIRING. , 1956, Proceedings of the National Academy of Sciences of the United States of America.

[75]  E. Jankowska,et al.  Subcortical effects of transcranial direct current stimulation in the rat , 2013, The Journal of physiology.

[76]  M. Bikson,et al.  Role of cortical cell type and morphology in subthreshold and suprathreshold uniform electric field stimulation in vitro , 2009, Brain Stimulation.

[77]  B. Krekelberg,et al.  Transcranial electrical stimulation over visual cortex evokes phosphenes with a retinal origin. , 2012, Journal of neurophysiology.

[78]  O. Creutzfeldt,et al.  Influence of transcortical d-c currents on cortical neuronal activity. , 1962, Experimental neurology.

[79]  C. Koch,et al.  Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats , 2010, The Journal of Neuroscience.

[80]  Terrence J. Sejnowski,et al.  Biophysical Basis for Three Distinct Dynamical Mechanisms of Action Potential Initiation , 2008, PLoS Comput. Biol..

[81]  Felipe Fregni,et al.  Understanding tDCS effects in schizophrenia: a systematic review of clinical data and an integrated computation modeling analysis , 2014, Expert review of medical devices.

[82]  J. Jamart,et al.  Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation , 2011, Journal of Neurology.

[83]  L. Parra,et al.  Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects , 2013, The Journal of physiology.