Synaptically Activated Ca2+ Waves in Layer 2/3 and Layer 5 Rat Neocortical Pyramidal Neurons

Calcium waves in layer 2/3 and layer 5 neocortical somatosensory pyramidal neurons were examined in slices from 2‐ to 8‐week‐old rats. Repetitive synaptic stimulation evoked a delayed, all‐or‐none [Ca2+]i increase primarily on the main dendritic shaft. This component was blocked by 1 mm (R,S)‐α‐methyl‐4‐carboxyphenylglycine (MCPG), 10 μm ryanodine, 1 mg ml−1 internal heparin, and was not blocked by 400 μm internal Ruthenium Red, indicating that it was due to Ca2+ release from internal stores by inositol 1,4,5‐trisphosphate (IP3) mobilized via activation of metabotropic glutamate receptors. Calcium waves were initiated on the apical shaft at sites between the soma to around the main branch point, mostly at insertion points of oblique dendrites, and spread in both directions along the shaft. In the proximal dendrites the peak amplitude of the resulting [Ca2+]i change was much larger than that evoked by a train of Na+ spikes. In distal dendrites the peak amplitude was comparable to the [Ca2+]i change due to a Ca2+ spike. IP3‐mediated Ca2+ release also was observed in the presence of the metabotropic agonists t‐ACPD and carbachol when backpropagating spikes were generated. Ca2+ entry through NMDA receptors was observed primarily on the oblique dendrites. The main differences between waves in neocortical neurons and in previously described hippocampal pyramidal neurons were, (a) Ca2+ waves in L5 neurons could be evoked further out along the main shaft, (b) Ca2+ waves extended slightly further out into the oblique dendrites and (c) higher concentrations of bath‐applied t‐ACPD and carbachol were required to generate Ca2+ release events by backpropagating action potentials.

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

[2]  W. N. Ross,et al.  Inositol 1,4,5-Trisphosphate (IP3)-Mediated Ca2+ Release Evoked by Metabotropic Agonists and Backpropagating Action Potentials in Hippocampal CA1 Pyramidal Neurons , 2000, The Journal of Neuroscience.

[3]  B. Sakmann,et al.  Patch-Pipette Recordings from the Soma, Dendrites, and Axon of Neurons in Brain Slices , 1995 .

[4]  Pankaj Sah,et al.  Nuclear Calcium Signaling Evoked by Cholinergic Stimulation in Hippocampal CA1 Pyramidal Neurons , 2002, The Journal of Neuroscience.

[5]  Karel Svoboda,et al.  Subliminal messages in hippocampal pyramidal cells , 2002, The Journal of physiology.

[6]  J. Miller,et al.  Calcium-binding protein distribution in the rat brain , 1982, Brain Research.

[7]  S Shimohama,et al.  A distinct form of calcium release down-regulates membrane excitability in neocortical pyramidal cells , 2002, Neuroscience.

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

[9]  S. M. Goldin,et al.  Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release. , 1991, Science.

[10]  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.

[11]  George J. Augustine,et al.  Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites , 1998, Nature.

[12]  M. Larkum,et al.  Signaling of Layer 1 and Whisker-Evoked Ca2+ and Na+ Action Potentials in Distal and Terminal Dendrites of Rat Neocortical Pyramidal Neurons In Vitro and In Vivo , 2002, The Journal of Neuroscience.

[13]  W. N. Ross,et al.  Synergistic Release of Ca2+ from IP3-Sensitive Stores Evoked by Synaptic Activation of mGluRs Paired with Backpropagating Action Potentials , 1999, Neuron.

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

[15]  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.

[16]  H. Markram.  A network of tufted layer 5 pyramidal neurons. , 1997, Cerebral cortex.

[17]  B. Sakmann,et al.  Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[18]  A. Friedman,et al.  Stepwise repolarization from Ca2+ plateaus in neocortical pyramidal cells: evidence for nonhomogeneous distribution of HVA Ca2+ channels in dendrites , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[19]  J. Zhu,et al.  Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1 and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites , 2000, The Journal of physiology.

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

[21]  B. Connors,et al.  Differential Regulation of Neocortical Synapses by Neuromodulators and Activity , 1997, Neuron.

[22]  D. McCormick,et al.  Control of firing mode of corticotectal and corticopontine layer V burst-generating neurons by norepinephrine, acetylcholine, and 1S,3R- ACPD , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[24]  S. H. Lee,et al.  Differences in Ca2+ buffering properties between excitatory and inhibitory hippocampal neurons from the rat , 2000, The Journal of physiology.

[25]  M. Berridge.  Neuronal Calcium Signaling , 1998, Neuron.

[26]  S. Kobayashi,et al.  Heparin inhibits the inositol 1,4,5-trisphosphate-dependent, but not the independent, calcium release induced by guanine nucleotide in vascular smooth muscle. , 1988, Biochemical and biophysical research communications.

[27]  D. McCormick,et al.  Actions of acetylcholine in the cerebral cortex and thalamus and implications for function. , 1993, Progress in brain research.

[28]  James Watras,et al.  Bell-shaped calcium-response curves of lns(l,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum , 1991, Nature.

[29]  K. Campbell,et al.  Purified ryanodine receptor from rabbit skeletal muscle is the calcium- release channel of sarcoplasmic reticulum , 1988, The Journal of general physiology.

[30]  R C Foehring,et al.  Characterization of pharmacologically identified voltage-gated calcium channel currents in acutely isolated rat neocortical neurons. II. Postnatal development. , 1995, Journal of neurophysiology.

[31]  B Sakmann,et al.  Spatial profile of dendritic calcium transients evoked by action potentials in rat neocortical pyramidal neurones. , 1995, The Journal of physiology.

[32]  Christian Lohmann,et al.  Transmitter-evoked local calcium release stabilizes developing dendrites , 2002, Nature.

[33]  K. Khodakhah,et al.  Inositol 1,4,5-Triphosphate-Evoked Responses in Midbrain Dopamine Neurons , 2000, The Journal of Neuroscience.

[34]  J. Lacaille,et al.  Membrane potential and intracellular Ca2+ oscillations activated by mGluRs in hippocampal stratum oriens/alveus interneurons. , 1999, Journal of neurophysiology.

[35]  J. Mullaney,et al.  Competitive, reversible, and potent antagonism of inositol 1,4,5-trisphosphate-activated calcium release by heparin. , 1988, Journal of Biological Chemistry.

[36]  W. N. Ross,et al.  Threshold conditions for synaptically evoking Ca(2+) waves in hippocampal pyramidal neurons. , 2002, Journal of neurophysiology.

[37]  M. Yeckel,et al.  Hippocampal mossy fiber activity evokes Ca2+ release in CA3 pyramidal neurons via a metabotropic glutamate receptor pathway , 2001, Neuroscience.

[38]  J. Pin,et al.  Pharmacology and functions of metabotropic glutamate receptors. , 1997, Annual review of pharmacology and toxicology.

[39]  D. Clapham,et al.  Calcium signaling , 1995, Cell.

[40]  N. Spitzer,et al.  Regulation of Calcineurin by Growth Cone Calcium Waves Controls Neurite Extension , 2000, The Journal of Neuroscience.

[41]  Graham L. Collingridge,et al.  Phosphatidylinositol 3 kinase regulates synapse specificity of hippocampal long-term depression , 2002, Nature Neuroscience.

[42]  É. Rousseau,et al.  Ryanodine modifies conductance and gating behavior of single Ca2+ release channel. , 1987, The American journal of physiology.

[43]  Arthur Konnerth,et al.  A new class of synaptic response involving calcium release in dendritic spines , 1998, Nature.

[44]  B. Ehrlich,et al.  Regulation of Ins(1,4,5)P3 receptor isoforms by endogenous modulators. , 2001, Trends in pharmacological sciences.

[45]  P. Delmas,et al.  Signaling Microdomains Define the Specificity of Receptor-Mediated InsP3 Pathways in Neurons , 2002, Neuron.

[46]  M. Iino,et al.  Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the guinea pig taenia caeci , 1990, The Journal of general physiology.

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

[48]  S. Snyder,et al.  Differential immunohistochemical localization of inositol 1,4,5- trisphosphate- and ryanodine-sensitive Ca2+ release channels in rat brain , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[49]  M. Poo,et al.  Calcium stores regulate the polarity and input specificity of synaptic modification , 2000, Nature.

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

[51]  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.

[52]  Y. Isomura,et al.  An IP3‐assisted form of Ca2+‐induced Ca2+ release in neocortical neurons , 2000, Neuroreport.

[53]  T. H. Brown,et al.  Metabotropic glutamate receptor activation induces calcium waves within hippocampal dendrites. , 1994, Journal of neurophysiology.

[54]  I. Parker,et al.  Potentiation of inositol trisphosphate‐induced Ca2+ mobilization in Xenopus oocytes by cytosolic Ca2+. , 1992, The Journal of physiology.

[55]  P. Stanton,et al.  Induction of Hippocampal Long-Term Depression Requires Release of Ca2+ from Separate Presynaptic and Postsynaptic Intracellular Stores , 1996, The Journal of Neuroscience.

[56]  W. N. Ross,et al.  Inositol 1 , 4 , 5-Trisphosphate ( IP 3 )-Mediated Ca 2 1 Release Evoked by Metabotropic Agonists and Backpropagating Action Potentials in Hippocampal CA 1 Pyramidal Neurons , 2000 .