Role of dendritic spines in action potential backpropagation: a numerical simulation study.

Two remarkable aspects of pyramidal neurons are their complex dendritic morphologies and the abundant presence of spines, small structures that are the sites of excitatory input. Although the channel properties of the dendritic shaft membrane have been experimentally probed, the influence of spine properties in dendritic signaling and action potential propagation remains unclear. To explore this we have performed multi-compartmental numerical simulations investigating the degree of consistency between experimental data on dendritic channel densities and backpropagation behavior, as well as the necessity and degree of influence of excitable spines. Our results indicate that measured densities of Na(+) channels in dendritic shafts cannot support effective backpropagation observed in apical dendrites due to suprathreshold inactivation. We demonstrate as a potential solution that Na(+) channels in spines at higher densities than those measured in the dendritic shaft can support extensive backpropagation. In addition, clustering of Na(+) channels in spines appears to enhance their effect due to their unique morphology. Finally, we show that changes in spine morphology significantly influence backpropagation efficacy. These results suggest that, by clustering sodium channels, spines may serve to control backpropagation.

[1]  D. Johnston,et al.  Slow Recovery from Inactivation of Na+ Channels Underlies the Activity-Dependent Attenuation of Dendritic Action Potentials in Hippocampal CA1 Pyramidal Neurons , 1997, The Journal of Neuroscience.

[2]  R. Yuste,et al.  Regulation of Spine Calcium Dynamics by Rapid Spine Motility Materials and Methods , 2022 .

[3]  D. Linden The Return of the Spike Postsynaptic Action Potentials and the Induction of LTP and LTD , 1999, Neuron.

[4]  William A Catterall,et al.  Muscarinic Modulation of Sodium Current by Activation of Protein Kinase C in Rat Hippocampal Neurons , 1996, Neuron.

[5]  I Segev,et al.  Signal Transfer in Passive Dendrites with Nonuniform Membrane Conductance , 1999, The Journal of Neuroscience.

[6]  B. Sakmann,et al.  Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons , 1997, The Journal of physiology.

[7]  F. Engert,et al.  Dendritic spine changes associated with hippocampal long-term synaptic plasticity , 1999, Nature.

[8]  D. Tank,et al.  In vivo dendritic calcium dynamics in deep-layer cortical pyramidal neurons , 1999, Nature Neuroscience.

[9]  J M Bekkers,et al.  Properties of voltage‐gated potassium currents in nucleated patches from large layer 5 cortical pyramidal neurons of the rat , 2000, The Journal of physiology.

[10]  B W Connors,et al.  Inhibitory control of excitable dendrites in neocortex. , 1995, Journal of neurophysiology.

[11]  Idan Segev,et al.  Excitable dendrites and spines: earlier theoretical insights elucidate recent direct observations , 1998, Trends in Neurosciences.

[12]  D. Johnston,et al.  Axonal Action-Potential Initiation and Na+ Channel Densities in the Soma and Axon Initial Segment of Subicular Pyramidal Neurons , 1996, The Journal of Neuroscience.

[13]  M. Häusser,et al.  Propagation of action potentials in dendrites depends on dendritic morphology. , 2001, Journal of neurophysiology.

[14]  W. Catterall,et al.  Functional modulation of brain sodium channels by protein kinase C phosphorylation. , 1991, Science.

[15]  D. Johnston,et al.  Neuromodulation of dendritic action potentials. , 1999, Journal of neurophysiology.

[16]  B. Sakmann,et al.  Patch-clamp recordings from the soma and dendrites of neurons in brain slices using infrared video microscopy , 1993, Pflügers Archiv.

[17]  N. Dascal,et al.  Activation of protein kinase C alters voltage dependence of a Na+ channel , 1991, Neuron.

[18]  D. Johnston,et al.  A Synaptically Controlled, Associative Signal for Hebbian Plasticity in Hippocampal Neurons , 1997, Science.

[19]  J. Magee,et al.  Somatic EPSP amplitude is independent of synapse location in hippocampal pyramidal neurons , 2000, Nature Neuroscience.

[20]  R. Yuste,et al.  Stereotyped position of local synaptic targets in neocortex. , 2001, Science.

[21]  Rafael Yuste,et al.  Calcium Dynamics of Spines Depend on Their Dendritic Location , 2002, Neuron.

[22]  D. Johnston,et al.  Dendritic calcium channels and hippocampal long‐term depression , 1996, Hippocampus.

[23]  P. Jonas,et al.  Distal initiation and active propagation of action potentials in interneuron dendrites. , 2000, Science.

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

[25]  D. Johnston,et al.  Characterization of single voltage‐gated Na+ and Ca2+ channels in apical dendrites of rat CA1 pyramidal neurons. , 1995, The Journal of physiology.

[26]  J. Caldwell,et al.  Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[27]  K. Svoboda,et al.  Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. , 1999, Science.

[28]  B. Sakmann,et al.  Action potential initiation and propagation in rat neocortical pyramidal neurons , 1997, The Journal of physiology.

[29]  T. Sejnowski,et al.  [Letters to nature] , 1996, Nature.

[30]  N. Spruston,et al.  Determinants of Voltage Attenuation in Neocortical Pyramidal Neuron Dendrites , 1998, The Journal of Neuroscience.

[31]  N. Spruston,et al.  Properties of slow, cumulative sodium channel inactivation in rat hippocampal CA1 pyramidal neurons. , 1999, Biophysical journal.

[32]  Idan Segev,et al.  Modeling back propagating action potential in weakly excitable dendrites of neocortical pyramidal cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[33]  S. B. Kater,et al.  Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function. , 1994, Annual review of neuroscience.

[34]  H. Markram,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997, Science.

[35]  C. Colbert,et al.  Arachidonic Acid Reciprocally Alters the Availability of Transient and Sustained Dendritic K+ Channels in Hippocampal CA1 Pyramidal Neurons , 1999, The Journal of Neuroscience.

[36]  W Rall,et al.  Computational study of an excitable dendritic spine. , 1988, Journal of neurophysiology.

[37]  Bernardo L. Sabatini,et al.  Analysis of calcium channels in single spines using optical fluctuation analysis , 2000, Nature.

[38]  Rafael Yuste,et al.  Ca2+ accumulations in dendrites of neocortical pyramidal neurons: An apical band and evidence for two functional compartments , 1994, Neuron.

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

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

[41]  N. Spruston,et al.  Action potential initiation and backpropagation in neurons of the mammalian CNS , 1997, Trends in Neurosciences.

[42]  B. Sakmann,et al.  Dendritic mechanisms underlying the coupling of the dendritic with the axonal action potential initiation zone of adult rat layer 5 pyramidal neurons , 2001, The Journal of physiology.

[43]  K. Harris,et al.  Three-dimensional structure of dendritic spines and synapses in rat hippocampus (CA1) at postnatal day 15 and adult ages: implications for the maturation of synaptic physiology and long-term potentiation. , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  G. Buzsáki,et al.  Somadendritic backpropagation of action potentials in cortical pyramidal cells of the awake rat. , 1998, Journal of neurophysiology.

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

[46]  B. Sakmann,et al.  Voltage‐gated K+ channels in layer 5 neocortical pyramidal neurones from young rats: subtypes and gradients , 2000, The Journal of physiology.

[47]  W. Denk,et al.  Mechanisms of Calcium Influx into Hippocampal Spines: Heterogeneity among Spines, Coincidence Detection by NMDA Receptors, and Optical Quantal Analysis , 1999, The Journal of Neuroscience.

[48]  S. Baer,et al.  Analysis of an excitable dendritic spine with an activity-dependent stem conductance , 1998, Journal of mathematical biology.

[49]  C. Colbert,et al.  Subthreshold inactivation of Na+ and K+ channels supports activity-dependent enhancement of back-propagating action potentials in hippocampal CA1. , 2001, Journal of neurophysiology.

[50]  M Migliore,et al.  Dendritic potassium channels in hippocampal pyramidal neurons , 2000, The Journal of physiology.

[51]  J Rinzel,et al.  Propagation of dendritic spikes mediated by excitable spines: a continuum theory. , 1991, Journal of neurophysiology.

[52]  D A Turner,et al.  Dendritic properties of hippocampal CA1 pyramidal neurons in the rat: Intracellular staining in vivo and in vitro , 1998, The Journal of comparative neurology.

[53]  M. Fischer,et al.  Rapid Actin-Based Plasticity in Dendritic Spines , 1998, Neuron.

[54]  C. Woolley,et al.  Gonadal steroids regulate dendritic spine density in hippocampal pyramidal cells in adulthood , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  W. Denk,et al.  Dendritic spines as basic functional units of neuronal integration , 1995, Nature.

[56]  G. Buzsáki,et al.  Hippocampal CA1 interneurons: an in vivo intracellular labeling study , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[57]  Daniel Johnston,et al.  Regulation of back-propagating action potentials in hippocampal neurons , 1999, Current Opinion in Neurobiology.

[58]  M Kawato,et al.  Electrical properties of dendritic spines with bulbous end terminals. , 1984, Biophysical journal.

[59]  W. N. Ross,et al.  Frequency-dependent propagation of sodium action potentials in dendrites of hippocampal CA1 pyramidal neurons. , 1995, Journal of neurophysiology.

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

[61]  D W Tank,et al.  Direct Measurement of Coupling Between Dendritic Spines and Shafts , 1996, Science.

[62]  J M Bekkers,et al.  Distribution and activation of voltage‐gated potassium channels in cell‐attached and outside‐out patches from large layer 5 cortical pyramidal neurons of the rat , 2000, The Journal of physiology.

[63]  D. Prince,et al.  Developmental changes in Na+ conductances in rat neocortical neurons: appearance of a slowly inactivating component. , 1988, Journal of neurophysiology.

[64]  D. Johnston,et al.  Active properties of neuronal dendrites. , 1996, Annual review of neuroscience.

[65]  Idan Segev,et al.  Signal enhancement in distal cortical dendrites by means of interactions between active dendritic spines. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[66]  S. R. Cajal Textura del Sistema Nervioso del Hombre y de los Vertebrados, 1899–1904 , 2019 .

[67]  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.

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

[69]  A. Matus,et al.  Actin-based plasticity in dendritic spines. , 2000, Science.

[70]  T. Poggio,et al.  A theoretical analysis of electrical properties of spines , 1983, Proceedings of the Royal Society of London. Series B. Biological Sciences.