Characterization of NMDA induced depression in rat hippocampus: involvement of AMPA and NMDA receptors

The involvement of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) vs. N-methyl-d-aspartate (NMDA) receptor mediated changes in NMDA-induced long-term depression (LTD) was assessed by monitoring isolated AMPA, isolated NMDA and composite field excitatory postsynaptic potentials (EPSP) in the CA1 area of acute rat hippocampal slices. Application of NMDA (20-50 microM) for 3-5 min led to LTD of both AMPA and NMDA receptor mediated EPSPs with near equal changes of the responses. However, AMPA EPSPs displayed a faster initial recovery than NMDA EPSPs. In addition, during the first 15-25 min after NMDA application, there was a superimposed potentiation of the later, but not early, part of AMPA EPSPs, implying a prolongation of waveform. In contrast, the NMDA EPSP waveform remained unaltered throughout the experiments. While it has been maintained that NMDA-induced depression is equivalent to stimulus-induced LTD, our results reveal additional complexity, suggesting a multitude of changes, most likely at the postsynaptic receptor level.

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

[2]  H. Wigström,et al.  Synaptic potentiation in the hippocampal CA1 region induced by application ofN-methyl-d-aspartate , 1991, Brain Research.

[3]  R. Carroll,et al.  NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity , 2002, Trends in Neurosciences.

[4]  Gary Lynch,et al.  Long-term potentiation alters the modulator pharmacology of AMPA-type glutamate receptors. , 2002, Journal of neurophysiology.

[5]  R. Nicoll,et al.  NMDA application potentiates synaptic transmission in the hippocampus , 1988, Nature.

[6]  H. Wigström,et al.  Comparing long‐term depression with pharmacologically induced synaptic attenuations in young rat hippocampi , 1997, Synapse.

[7]  H. Wigström,et al.  The complementary nature of long-term depression and potentiation revealed by dual component excitatory postsynaptic potentials in hippocampal slices from young rats , 1995, Neuroscience.

[8]  G. Lynch,et al.  Evidence that changes in spine neck resistance are not responsible for expression of LTP , 1991, Synapse.

[9]  K. Hsu,et al.  Characterization of the Mechanism Underlying the Reversal of Long Term Potentiation by Low Frequency Stimulation at Hippocampal CA1 Synapses* 210 , 2001, The Journal of Biological Chemistry.

[10]  B. Gustafsson,et al.  TEA elicits two distinct potentiations of synaptic transmission in the CA1 region of the hippocampal slice , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  T. Bliss,et al.  Synaptic plasticity in the hippocampus , 1979, Trends in Neurosciences.

[12]  Mark F Bear,et al.  NMDA Induces Long-Term Synaptic Depression and Dephosphorylation of the GluR1 Subunit of AMPA Receptors in Hippocampus , 1998, Neuron.

[13]  B. Gustafsson,et al.  Changes in field excitatory postsynaptic potential shape induced by tetanization in the ca1 region of the guinea-pig hippocampal slice , 1990, Neuroscience.

[14]  Yu Tian Wang,et al.  Regulation of NMDA receptors by tyrosine kinases and phosphatases , 1994, Nature.

[15]  Robert C. Malenka,et al.  Synaptic plasticity in the hippocampus: LTP and LTD , 1994, Cell.

[16]  Robert C. Malenka,et al.  Independent mechanisms for long-term depression of AMPA and NMDA responses , 1995, Neuron.

[17]  R. Nicoll,et al.  Evidence for all‐or‐none regulation of neurotransmitter release: implications for long‐term potentiation. , 1993, The Journal of physiology.

[18]  F Asztely,et al.  Dissociation between long‐term potentiation and associated changes in field epsp waveform in the hippocampal CA1 region: An in vitro study in guinea pig brain slices , 1994, Hippocampus.

[19]  G. Ramakers,et al.  Chemical LTD in the CA1 field of the hippocampus from young and mature rats , 1999, The European journal of neuroscience.

[20]  G. Ramakers,et al.  N-methyl-d-aspartate-induced long-term depression is associated with a decrease in postsynaptic protein kinase C substrate phosphorylation in rat hippocampal slices , 2002, Neuroscience Letters.

[21]  R. Huganir,et al.  Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long-term depression , 2001, Proceedings of the National Academy of Sciences of the United States of America.