Dendritic signals from rat hippocampal CA1 pyramidal neurons during coincident pre‐ and post‐synaptic activity: a combined voltage‐ and calcium‐imaging study

The non‐linear and spatially inhomogeneous interactions of dendritic membrane potential signals that represent the first step in the induction of activity‐dependent long‐term synaptic plasticity are not fully understood, particularly in dendritic regions which are beyond the reach of electrode measurements. We combined voltage‐sensitive‐dye recordings and Ca2+ imaging of hippocampal CA1 pyramidal neurons to study large regions of the dendritic arbor, including branches of small diameter (distal apical and oblique dendrites). Dendritic membrane potential transients were monitored at high spatial resolution and correlated with supra‐linear [Ca2+]i changes during one cycle of a repetitive patterned stimulation protocol that typically results in the induction of long‐term potentiation (LTP). While the increase in the peak membrane depolarization during coincident pre‐ and post‐synaptic activity was required for the induction of supra‐linear [Ca2+]i signals shown to be necessary for LTP, the change in the baseline‐to‐peak amplitude of the backpropagating dendritic action potential (bAP) was not critical in this process. At different dendritic locations, the baseline‐to‐peak amplitude of the bAP could be either increased, decreased or unaltered at sites where EPSP–AP pairing evoked supra‐linear summation of [Ca2+]i transients. We suggest that modulations in the bAP baseline‐to‐peak amplitude by local EPSPs act as a mechanism that brings the membrane potential into the optimal range for Ca2+ influx through NMDA receptors (0 to −15 mV); this may require either boosting or the reduction of the bAP, depending on the initial size of both signals.

[1]  Jian-Young Wu,et al.  Multisite Optical Measurement of Membrane Potential , 1990 .

[2]  H. Markram,et al.  Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[4]  O. Garaschuk,et al.  Fractional Ca2+ currents through somatic and dendritic glutamate receptor channels of rat hippocampal CA1 pyramidal neurones. , 1996, The Journal of physiology.

[5]  T. Bliss,et al.  Single Synaptic Events Evoke NMDA Receptor–Mediated Release of Calcium from Internal Stores in Hippocampal Dendritic Spines , 1999, Neuron.

[6]  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.

[7]  J. Connor,et al.  Micromolar Ca2+ transients in dendritic spines of hippocampal pyramidal neurons in brain slice , 1995, Neuron.

[8]  S. Antic,et al.  Fast optical recordings of membrane potential changes from dendrites of pyramidal neurons. , 1999, Journal of neurophysiology.

[9]  S. Redman,et al.  Different calcium sources are narrowly tuned to the induction of different forms of LTP. , 2002, Journal of neurophysiology.

[10]  S. Antic,et al.  Optical signals from neurons with internally applied voltage-sensitive dyes , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  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.

[12]  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.

[13]  Leonardo Sacconi,et al.  Optical recording of fast neuronal membrane potential transients in acute mammalian brain slices by second-harmonic generation microscopy. , 2005, Journal of neurophysiology.

[14]  Matt Wachowiak,et al.  Fast multisite optical measurement of membrane potential: three examples , 1999 .

[15]  G. Stuart,et al.  Site of Action Potential Initiation in Layer 5 Pyramidal Neurons , 2006, The Journal of Neuroscience.

[16]  Nace L. Golding,et al.  Dendritic Calcium Spike Initiation and Repolarization Are Controlled by Distinct Potassium Channel Subtypes in CA1 Pyramidal Neurons , 1999, The Journal of Neuroscience.

[17]  W. N. Ross,et al.  Spatial Segregation and Interaction of Calcium Signalling Mechanisms in Rat Hippocampal CA1 Pyramidal Neurons , 2002, The Journal of physiology.

[18]  W. N. Ross,et al.  Synaptically activated increases in Ca2+ concentration in hippocampal CA1 pyramidal cells are primarily due to voltage-gated Ca2+ channels , 1992, Neuron.

[19]  Takeshi Aihara,et al.  Spatial Localization of Synapses Required for Supralinear Summation of Action Potentials and EPSPs , 2004, Journal of Computational Neuroscience.

[20]  G. Stuart,et al.  Backpropagation of Physiological Spike Trains in Neocortical Pyramidal Neurons: Implications for Temporal Coding in Dendrites , 2000, The Journal of Neuroscience.

[21]  W. N. Ross,et al.  Changes in absorption, fluorescence, dichroism, and birefringence in stained giant axons: Optical measurement of membrane potential , 1977, The Journal of Membrane Biology.

[22]  A. Konnerth,et al.  NMDA Receptor-Mediated Subthreshold Ca2+ Signals in Spines of Hippocampal Neurons , 2000, The Journal of Neuroscience.

[23]  G. Salama,et al.  A naphthyl analog of the aminostyryl pyridinium class of potentiometric membrane dyes shows consistent sensitivity in a variety of tissue, cell, and model membrane preparations , 1992, The Journal of Membrane Biology.

[24]  B. Sakmann,et al.  Spine Ca2+ Signaling in Spike-Timing-Dependent Plasticity , 2006, The Journal of Neuroscience.

[25]  Shigeo Watanabe,et al.  Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[26]  G. M. Rose,et al.  Induction of hippocampal long-term potentiation using physiologically patterned stimulation , 1986, Neuroscience Letters.

[27]  E. Neher,et al.  Calcium gradients and buffers in bovine chromaffin cells. , 1992, The Journal of physiology.

[28]  K. Svoboda,et al.  Estimating intracellular calcium concentrations and buffering without wavelength ratioing. , 2000, Biophysical journal.

[29]  R. H. Evans,et al.  Excitatory amino acid transmitters. , 1981, Annual review of pharmacology and toxicology.

[30]  N. Spruston,et al.  Postsynaptic depolarization requirements for LTP and LTD: a critique of spike timing-dependent plasticity , 2005, Nature Neuroscience.

[31]  R. Nicoll,et al.  Long-term potentiation--a decade of progress? , 1999, Science.

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

[33]  P. J. Sjöström,et al.  Rate, Timing, and Cooperativity Jointly Determine Cortical Synaptic Plasticity , 2001, Neuron.

[34]  S. Antic,et al.  Functional profile of the giant metacerebral neuron of Helix aspersa: temporal and spatial dynamics of electrical activity in situ , 2000, The Journal of physiology.

[35]  Bert Sakmann,et al.  Backpropagating action potentials in neurones: measurement, mechanisms and potential functions. , 2005, Progress in biophysics and molecular biology.

[36]  Michele Migliore,et al.  Normalization of Ca2+ Signals by Small Oblique Dendrites of CA1 Pyramidal Neurons , 2003, The Journal of Neuroscience.

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

[38]  Bert Sakmann,et al.  Supralinear Ca2+ Influx into Dendritic Tufts of Layer 2/3 Neocortical Pyramidal Neurons In Vitro and In Vivo , 2003, The Journal of Neuroscience.

[39]  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.

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

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

[42]  M. Jackson,et al.  Heterogeneous spatial patterns of long‐term potentiation in rat hippocampal slices , 2006, The Journal of physiology.

[43]  T. Bliss,et al.  Optical Quantal Analysis Reveals a Presynaptic Component of LTP at Hippocampal Schaffer-Associational Synapses , 2003, Neuron.

[44]  B. Sakmann,et al.  Single Spine Ca2+ Signals Evoked by Coincident EPSPs and Backpropagating Action Potentials in Spiny Stellate Cells of Layer 4 in the Juvenile Rat Somatosensory Barrel Cortex , 2004, The Journal of Neuroscience.

[45]  Stephen J Redman,et al.  Spatial segregation of neuronal calcium signals encodes different forms of LTP in rat hippocampus , 2006, The Journal of physiology.

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

[47]  A. Konnerth,et al.  Fractional contribution of calcium to the cation current through glutamate receptor channels , 1993, Neuron.

[48]  D. Tank,et al.  Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation , 1989, Nature.

[49]  B. Sakmann,et al.  Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[50]  K. Svoboda,et al.  The Life Cycle of Ca2+ Ions in Dendritic Spines , 2002, Neuron.

[51]  E. Kandel,et al.  Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization. , 1994, Learning & memory.

[52]  P. J. Sjöström,et al.  A Cooperative Switch Determines the Sign of Synaptic Plasticity in Distal Dendrites of Neocortical Pyramidal Neurons , 2006, Neuron.

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

[54]  R S Zucker,et al.  Postsynaptic calcium is sufficient for potentiation of hippocampal synaptic transmission. , 1988, Science.

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

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

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

[58]  Srdjan D Antic,et al.  Action Potentials in Basal and Oblique Dendrites of Rat Neocortical Pyramidal Neurons , 2003, The Journal of physiology.

[59]  B. Sakmann,et al.  Ca2+ buffering and action potential-evoked Ca2+ signaling in dendrites of pyramidal neurons. , 1996, Biophysical journal.

[60]  W. N. Ross,et al.  The spread of Na+ spikes determines the pattern of dendritic Ca2+ entry into hippocampal neurons , 1992, Nature.

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

[62]  Rafael Yuste,et al.  Imaging membrane potential in dendritic spines. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[63]  C. Stevens,et al.  Presynaptic mechanism for long-term potentiation in the hippocampus , 1990, Nature.

[64]  M. Häusser,et al.  Dendritic coincidence detection of EPSPs and action potentials , 2001, Nature Neuroscience.

[65]  Wei R Chen,et al.  Voltage Imaging from Dendrites of Mitral Cells: EPSP Attenuation and Spike Trigger Zones , 2004, The Journal of Neuroscience.

[66]  B. Kampa,et al.  Calcium Spikes in Basal Dendrites of Layer 5 Pyramidal Neurons during Action Potential Bursts , 2006, The Journal of Neuroscience.

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

[68]  K. Holthoff,et al.  Single‐shock LTD by local dendritic spikes in pyramidal neurons of mouse visual cortex , 2004, The Journal of physiology.