Ion channel properties underlying axonal action potential initiation in pyramidal neurons

A high density of Na+ channels in the axon hillock, or initial segment, is believed to determine the threshold for action potential initiation in neurons. Here we report evidence for an alternative mechanism that lowers the threshold in the axon. We investigated properties and distributions of ion channels in outside-out patches from axons and somata of layer 5 pyramidal neurons in rat neocortical slices. Na+ channels in axonal patches (〈30 μm from the soma) were activated by 7 mV less depolarization than were somatic Na+ channels. A-type K+ channels, which were prominent in somatic and dendritic patches, were rarely seen in axonal patches. We incorporated these findings into numerical simulations which indicate that biophysical properties of axonal channels, rather than a high density of channels in the initial segment, are most likely to determine the lowest threshold for action potential initiation.

[1]  D. Ottoson,et al.  The site of impulse initiation in a nerve cell of a crustacean stretch receptor , 1958, The Journal of physiology.

[2]  Sanford L. Palay,et al.  THE AXON HILLOCK AND THE INITIAL SEGMENT , 1968, The Journal of cell biology.

[3]  J. Cooley,et al.  Action potential of the motorneuron , 1973 .

[4]  W. Catterall,et al.  Localization of sodium channels in cultured neural cells , 1981, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  J W Moore,et al.  On the site of impulse initiation in a neurone. , 1983, The Journal of physiology.

[6]  P. Gogan,et al.  Comparison of antidromic and orthodromic action potentials of identified motor axons in the cat's brain stem. , 1983, The Journal of physiology.

[7]  J W Moore,et al.  Action potential propagation and threshold parameters in inhomogeneous regions of squid axons. , 1983, The Journal of physiology.

[8]  J. Rosenbluth,et al.  Plasma membrane structure at the axon hillock, initial segment and cell body of frog dorsal root ganglion cells , 1985, Journal of neurocytology.

[9]  E. Elson,et al.  Distribution and lateral mobility of voltage-dependent sodium channels in neurons [published erratum appears in J Cell Biol 1989 May;108(5):preceding 2001] , 1988, The Journal of cell biology.

[10]  I Fariñas,et al.  Patterns of synaptic input on corticocortical and corticothalamic cells in the cat visual cortex. II. The axon initial segment , 1991, The Journal of comparative neurology.

[11]  I Fariñas,et al.  Patterns of synaptic input on corticocortical and corticothalamic cells in the cat visual cortex. I. The cell body , 1991, The Journal of comparative neurology.

[12]  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.

[13]  P. Adams The platonic neuron gets the hots , 1992, Current Biology.

[14]  P. L. Carras,et al.  Site of action potential initiation in amphibian retinal ganglion cells. , 1992, Journal of neurophysiology.

[15]  Michael L. Hines,et al.  NEURON — A Program for Simulation of Nerve Equations , 1993 .

[16]  P. Somogyi,et al.  Physiological properties of anatomically identified axo-axonic cells in the rat hippocampus. , 1994, Journal of neurophysiology.

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

[18]  Bartlett W. Mel,et al.  Information Processing in Dendritic Trees , 1994, Neural Computation.

[19]  Clay M. Armstrong,et al.  Dendritic Function: Where does it all begin? , 1994, Current Biology.

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

[21]  J. Lambert,et al.  Regenerative properties of pyramidal cell dendrites in area CA1 of the rat hippocampus. , 1995, The Journal of physiology.

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

[23]  P. Somogyi,et al.  Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons , 1995, Nature.

[24]  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.

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

[26]  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.

[27]  D. Zecevic,et al.  Multiple spike-initiation zones in single neurons revealed by voltage-sensitive dyes , 1996, Nature.

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

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

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

[31]  D. Kleinfeld,et al.  In vivo dendritic calcium dynamics in neocortical pyramidal neurons , 1997, Nature.

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

[33]  M. Gutnick,et al.  Activation of protein kinase C increases neuronal excitability by regulating persistent Na+ current in mouse neocortical slices. , 1998, Journal of neurophysiology.

[34]  W. Newsome,et al.  The Variable Discharge of Cortical Neurons: Implications for Connectivity, Computation, and Information Coding , 1998, The Journal of Neuroscience.

[35]  M. Larkum,et al.  Modeling action potential initiation and back-propagation in dendrites of cultured rat motoneurons. , 1998, Journal of neurophysiology.

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

[37]  C. Paillart,et al.  Specific distribution of sodium channels in axons of rat embryo spinal motoneurones , 1999, The Journal of physiology.

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

[39]  J. Trimmer,et al.  K+ channel distribution and clustering in developing and hypomyelinated axons of the optic nerve , 1999, Journal of neurocytology.

[40]  F. Kloosterman,et al.  Apical and basal orthodromic population spikes in hippocampal CA1 in vivo show different origins and patterns of propagation. , 2001, Journal of neurophysiology.

[41]  T. Bliss,et al.  A decrease in firing threshold observed after induction of the EPSP-spike (E-S) component of long-term potentiation in rat hippocampal slices , 2004, Experimental Brain Research.