On the Initiation and Propagation of Dendritic Spikes in CA1 Pyramidal Neurons

Under certain conditions, regenerative voltage spikes can be initiated locally in the dendrites of CA1 pyramidal neurons. These are interesting events that could potentially provide neurons with additional computational abilities. Using whole-cell dendritic recordings from the distal apical trunk and proximal tuft regions and realistic computer modeling, we have determined that highly synchronized and moderately clustered inputs are required for dendritic spike initiation: ∼50 synaptic inputs spread over 100 μm of the apical trunk/tuft need to be activated within 3 msec. Dendritic spikes are characterized by a more depolarized voltage threshold than at the soma [-48 ± 1 mV (n = 30) vs -56 ± 1 mV (n = 7), respectively] and are mainly generated and shaped by dendritic Na+ and K+ currents. The relative contribution of AMPA and NMDA currents is also important in determining the actual spatiotemporal requirements for dendritic spike initiation. Once initiated, dendritic spikes can easily reach the soma, but their propagation is only moderately strong, so that it can be modulated by physiologically relevant factors such as changes in the Vm and the ionic composition of the extracellular solution. With effective spike propagation, an extremely short-latency neuronal output is produced for greatly reduced input levels. Therefore, dendritic spikes function as efficient detectors of specific input patterns, ensuring that the neuronal response to high levels of input synchrony is a precisely timed action potential output.

[1]  L H HAMLYN,et al.  Action potentials of the pyramidal neurones in the hippocampus of the rabbit , 1955, The Journal of physiology.

[2]  E. Kandel,et al.  ELECTROPHYSIOLOGY OF HIPPOCAMPAL NEURONS: IV. FAST PREPOTENTIALS. , 1961, Journal of neurophysiology.

[3]  E. Kandel,et al.  Electrophysiology of hippocampal neurons. I. Sequential invasion and synaptic organization. , 1961, Journal of neurophysiology.

[4]  B. L. Ginsborg THE PHYSIOLOGY OF SYNAPSES , 1964 .

[5]  J. Eccles The Physiology of Synapses , 1964, Springer Berlin Heidelberg.

[6]  T A Pedley,et al.  The role of extracellular potassium in hippocampal epilepsy. , 1976, Archives of neurology.

[7]  M. Mauk,et al.  Activity-evoked increases in extracellular potassium modulate presynaptic excitability in the CA1 region of the hippocampus. , 1987, Journal of neurophysiology.

[8]  P. Schwartzkroin,et al.  Electrophysiology of Hippocampal Neurons , 1987 .

[9]  R. Keep,et al.  Brain fluid calcium concentration and response to acute hypercalcaemia during development in the rat. , 1988, The Journal of physiology.

[10]  W. N. Ross,et al.  High time resolution fluorescence imaging with a CCD camera , 1991, Journal of Neuroscience Methods.

[11]  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.

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

[13]  B. McNaughton,et al.  Reactivation of hippocampal ensemble memories during sleep. , 1994, Science.

[14]  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.

[15]  K. I. Blum,et al.  Impaired Hippocampal Representation of Space in CA1-Specific NMDAR1 Knockout Mice , 1996, Cell.

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

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

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

[19]  B. McNaughton,et al.  Memory reprocessing in corticocortical and hippocampocortical neuronal ensembles. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

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

[21]  G M Shepherd,et al.  Forward and backward propagation of dendritic impulses and their synaptic control in mitral cells. , 1997, Science.

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

[23]  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.

[24]  G. Buzsáki,et al.  Dendritic Spikes Are Enhanced by Cooperative Network Activity in the Intact Hippocampus , 1998, The Journal of Neuroscience.

[25]  D. Johnston,et al.  Protein kinase C activation decreases activity-dependent attenuation of dendritic Na+ current in hippocampal CA1 pyramidal neurons. , 1998, Journal of neurophysiology.

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

[27]  B. McNaughton,et al.  Reactivation of Hippocampal Cell Assemblies: Effects of Behavioral State, Experience, and EEG Dynamics , 1999, The Journal of Neuroscience.

[28]  J. Magee Dendritic Ih normalizes temporal summation in hippocampal CA1 neurons , 1999, Nature Neuroscience.

[29]  Jeffrey C. Magee,et al.  Dendritic I h normalizes temporal summation in hippocampal CA 1 neurons , 1999 .

[30]  R. Yuste,et al.  Linear Summation of Excitatory Inputs by CA1 Pyramidal Neurons , 1999, Neuron.

[31]  J. Csicsvari,et al.  Oscillatory Coupling of Hippocampal Pyramidal Cells and Interneurons in the Behaving Rat , 1999, The Journal of Neuroscience.

[32]  J. Magee,et al.  Dendritic voltage-gated ion channels regulate the action potential firing mode of hippocampal CA1 pyramidal neurons. , 1999, Journal of neurophysiology.

[33]  J. Magee Dendritic lh normalizes temporal summation in hippocampal CA1 neurons. , 1999, Nature neuroscience.

[34]  D. Johnston,et al.  Voltage-dependent properties of dendrites that eliminate location-dependent variability of synaptic input. , 1999, Journal of neurophysiology.

[35]  J. Lisman Relating Hippocampal Circuitry to Function Recall of Memory Sequences by Reciprocal Dentate–CA3 Interactions , 1999, Neuron.

[36]  N. Spruston,et al.  Diversity and dynamics of dendritic signaling. , 2000, Science.

[37]  Friedrich Huisken,et al.  Distal Initiation and Active Propagation of Action Potentials in Interneuron Dendrites , 2000 .

[38]  J. Schiller,et al.  NMDA spikes in basal dendrites of cortical pyramidal neurons , 2000, Nature.

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

[40]  C. Gray,et al.  Dynamic spike threshold reveals a mechanism for synaptic coincidence detection in cortical neurons in vivo. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[41]  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.

[42]  H. Robinson,et al.  Postsynaptic Variability of Firing in Rat Cortical Neurons: The Roles of Input Synchronization and Synaptic NMDA Receptor Conductance , 2000, The Journal of Neuroscience.

[43]  J. Kao,et al.  Compartmentalized and Binary Behavior of Terminal Dendrites in Hippocampal Pyramidal Neurons , 2001, Science.

[44]  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.

[45]  B. Hille,et al.  Ionic channels of excitable membranes , 2001 .

[46]  T. Sejnowski,et al.  Fluctuating synaptic conductances recreate in vivo-like activity in neocortical neurons , 2001, Neuroscience.

[47]  Bartlett W. Mel,et al.  Impact of Active Dendrites and Structural Plasticity on the Memory Capacity of Neural Tissue , 2001, Neuron.

[48]  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.

[49]  J. Lisman,et al.  Pathway-Specific Properties of AMPA and NMDA-Mediated Transmission in CA1 Hippocampal Pyramidal Cells , 2002, The Journal of Neuroscience.

[50]  Nace L. Golding,et al.  Dendritic spikes as a mechanism for cooperative long-term potentiation , 2002, Nature.

[51]  G. Stuart,et al.  Dependence of EPSP Efficacy on Synapse Location in Neocortical Pyramidal Neurons , 2002, Science.

[52]  Ion channel properties underlying axonal action potential initiation in pyramidal neurons , 2002, Nature Neuroscience.

[53]  A. Polsky,et al.  Submillisecond Precision of the Input-Output Transformation Function Mediated by Fast Sodium Dendritic Spikes in Basal Dendrites of CA1 Pyramidal Neurons , 2003, The Journal of Neuroscience.

[54]  J. Magee,et al.  Mechanism of the distance‐dependent scaling of Schaffer collateral synapses in rat CA1 pyramidal neurons , 2003, The Journal of physiology.

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

[56]  D. Johnston,et al.  Distance-dependent modifiable threshold for action potential back-propagation in hippocampal dendrites. , 2003, Journal of neurophysiology.

[57]  Michele Migliore,et al.  Dendritic Ih Selectively Blocks Temporal Summation of Unsynchronized Distal Inputs in CA1 Pyramidal Neurons , 2004, Journal of Computational Neuroscience.

[58]  Daniel Johnston,et al.  LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites , 2004, Nature Neuroscience.

[59]  Bartlett W. Mel,et al.  Computational subunits in thin dendrites of pyramidal cells , 2004, Nature Neuroscience.