Long-term potentiation of hippocampal mossy fiber synapses is blocked by postsynaptic injection of calcium chelators

The role of intracellular calcium in an APV-insensitive form of long-term potentiation (LTP) has been studied at the hippocampal mossy fiber synapse. Intracellular calcium was buffered by iontophoretic injection of either BAPTA or QUIN-2, into CA3 pyramidal neurons. The slow calcium-dependent after hyperpolarization was used as an indicator of buffering. LTP was elicited in control and in APV-treated cells (6/6 and 4/5 cell, respectively). In contrast, LTP was observed in only 2/9 BAPTA-loaded cells and in 1/4 QUIN-2-loaded cells. The magnitude of LTP for control and APV-treated cells were not significantly different, but both groups showed significantly greater LTP than BAPTA-loaded cells. These results suggest that an increase in postsynaptic calcium is required for the induction of mossy fiber LTP.

[1]  S. Provencher A Fourier method for the analysis of exponential decay curves. , 1976, Biophysical journal.

[2]  Stephen J. Smith Progress on LTP at hippocampal synapses: a post-synaptic Ca2+ trigger for memory storage? , 1987, Trends in Neurosciences.

[3]  S. Provencher,et al.  An eigenfunction expansion method for the analysis of exponential decay curves , 1976 .

[4]  Gary Lynch,et al.  The relationship between extracellular calcium concentrations and the induction of hippocampal long-term potentiation , 1979, Brain Research.

[5]  G. F. Ayala,et al.  A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus , 1982, Neuroscience Letters.

[6]  G. Lynch,et al.  Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5 , 1986, Nature.

[7]  R Y Tsien,et al.  Intracellular measurements of ion activities. , 1983, Annual review of biophysics and bioengineering.

[8]  D. Johnston,et al.  Cholinergic and Noradrenergic Modulation of Long-term Potentiation in Hippocampal CA3 Neurons , 1989 .

[9]  J. Eccles Calcium in long-term potentiation as a model for memory , 1983, Neuroscience.

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

[11]  M. Berridge,et al.  Excitation and adaptation of Limulus ventral photoreceptors by inositol 1,4,5 triphosphate result from a rise in intracellular calcium , 1986, The Journal of general physiology.

[12]  D. Johnston,et al.  Noradrenergic enhancement of long-term potentiation at mossy fiber synapses in the hippocampus. , 1988, Journal of neurophysiology.

[13]  H. Haas,et al.  A simple perfusion chamber for the study of nervous tissue slices in vitro , 1979, Journal of Neuroscience Methods.

[14]  D. A. Brown,et al.  Muscarine affects calcium-currents in rat hippocampal pyramidal cells in vitro , 1987, Neuroscience Letters.

[15]  Stephen J. Smith,et al.  NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones , 1986, Nature.

[16]  R. D. Purves,et al.  Microelectrode methods for intracellular recording and ionophoresis , 1981 .

[17]  R Y Tsien,et al.  New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. , 1980, Biochemistry.

[18]  T. H. Brown,et al.  Interpretation of voltage-clamp measurements in hippocampal neurons. , 1983, Journal of neurophysiology.

[19]  C. Cotman,et al.  Long-term potentiation of guinea pig mossy fiber responses is not blocked by N-methyl d-aspartate antagonists , 1986, Neuroscience Letters.

[20]  J. Barker,et al.  Whole-cell patch-clamp analysis of voltage-dependent calcium conductances in cultured embryonic rat hippocampal neurons. , 1989, Journal of neurophysiology.

[21]  G. Collingridge,et al.  Excitatory amino acids in synaptic transmission in the Schaffer collateral‐commissural pathway of the rat hippocampus. , 1983, The Journal of physiology.

[22]  R. Tsien Fluorescent probes of cell signaling. , 1989, Annual review of neuroscience.

[23]  T. H. Brown,et al.  Voltage-clamp analysis of mossy fiber synaptic input to hippocampal neurons. , 1983, Journal of neurophysiology.

[24]  D. Johnston,et al.  Muscarinic depression of long-term potentiation in CA3 hippocampal neurons. , 1988, Science.

[25]  D. Johnston,et al.  Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus. , 1984, Science.

[26]  R. Nicoll,et al.  The current excitement in long term potentiation , 1988, Neuron.

[27]  M. Mayer,et al.  Permeation and block of N‐methyl‐D‐aspartic acid receptor channels by divalent cations in mouse cultured central neurones. , 1987, The Journal of physiology.

[28]  G. Lynch,et al.  Intracellular injections of EGTA block induction of hippocampal long-term potentiation , 1983, Nature.