Chemical LTD in the CA1 field of the hippocampus from young and mature rats

Within the hippocampal formation, two forms of long‐lasting synaptic plasticity, long‐term potentiation (LTP) and long‐term depression (LTD), can be induced which require the activation of NMDA receptors. Interestingly, it has been shown that both LTP and LTD are reduced in adult animals. Recently, a new chemical protocol has been described which elicits LTD in the CA1 field of the hippocampus. Application of 20 μm NMDA for 3 min results in a stable and long‐lasting decrease in the evoked synaptic responses. We used this protocol to induce LTD in hippocampal slices from young and adult rats and show that this form of LTD is AP5‐sensitive and can be blocked by the protein phosphatase inhibitor cyclosporin A in slices from adult animals. In contrast to electrical LTD (induced by prolonged low frequency stimulation), the extent of chemical LTD was not different between the young and adult rats. These findings indicate that the intracellular signal transduction cascades involved in long‐lasting synaptic depression are still intact in adult animals.

[1]  R. Malenka,et al.  Involvement of a calcineurin/ inhibitor-1 phosphatase cascade in hippocampal long-term depression , 1994, Nature.

[2]  B. Sakmann,et al.  Developmental and regional expression in the rat brain and functional properties of four NMDA receptors , 1994, Neuron.

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

[4]  S. Vicini,et al.  Regional and Ontogenic Expression of the NMDA Receptor Subunit NR2D Protein in Rat Brain Using a Subunit‐Specific Antibody , 1996, Journal of neurochemistry.

[5]  R. Nicoll,et al.  Ca2+ Signaling Requirements for Long-Term Depression in the Hippocampus , 1996, Neuron.

[6]  O. Krishtal,et al.  NMDA receptor agonists selectively block N-type calcium channels in hippocampal neurons , 1991, Nature.

[7]  S Laroche,et al.  Stimulation at 1-5 Hz does not produce long-term depression or depotentiation in the hippocampus of the adult rat in vivo. , 1995, Journal of neurophysiology.

[8]  D. Johnston,et al.  N-methyl-D-aspartate receptor activation increases cAMP levels and voltage-gated Ca2+ channel activity in area CA1 of hippocampus. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[9]  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.

[10]  W Singer,et al.  Different threshold levels of postsynaptic [Ca2+]i have to be reached to induce LTP and LTD in neocortical pyramidal cells , 1996, Journal of Physiology-Paris.

[11]  P. Stanton,et al.  Priming of homosynaptic long-term depression in hippocampus by previous synaptic activity. , 1993, Neuroreport.

[12]  M. Paupard,et al.  Developmental regulation and cell-specific expression of N-methyl-d-aspartate receptor splice variants in rat hippocampus , 1997, Neuroscience.

[13]  B. Alger,et al.  GABAergic and developmental influences on homosynaptic LTD and depotentiation in rat hippocampus , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[15]  M. Bear,et al.  Synaptic plasticity: LTP and LTD , 1994, Current Opinion in Neurobiology.

[16]  Susumu Tonegawa,et al.  Synaptic plasticity, place cells and spatial memory: study with second generation knockouts , 1997, Trends in Neurosciences.

[17]  W. Singer,et al.  Relation Between Dendritic Ca2+ Levels and the Polarity of Synaptic Long‐term Modifications in Rat Visual Cortex Neurons , 1997, The European journal of neuroscience.

[18]  L. Jarrard What does the hippocampus really do? , 1995, Behavioural Brain Research.

[19]  G. Biessels,et al.  Increasing age reduces expression of long-term depression and dynamic range of transmission plasticity in CA1 field of the rat hippocampus , 1998, Neuroscience.

[20]  J. Kunz,et al.  Cyclosporin A, FK506 and rapamycin: more than just immunosuppression. , 1993, Trends in biochemical sciences.

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

[22]  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.

[23]  E. Costa,et al.  Learning impairment in rats by N-methyl-D-aspartate receptor antagonists , 1988, Neuropharmacology.

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

[25]  S. Tonegawa,et al.  The Essential Role of Hippocampal CA1 NMDA Receptor–Dependent Synaptic Plasticity in Spatial Memory , 1996, Cell.

[26]  R K Wong,et al.  Sustained dendritic gradients of Ca2+ induced by excitatory amino acids in CA1 hippocampal neurons. , 1988, Science.

[27]  R. Malenka,et al.  An essential role for protein phosphatases in hippocampal long-term depression. , 1993, Science.

[28]  Mark F Bear,et al.  Involvement of a Postsynaptic Protein Kinase A Substrate in the Expression of Homosynaptic Long-Term Depression , 1998, Neuron.

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

[30]  G. Biessels,et al.  Place Learning and Hippocampal Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats , 1996, Diabetes.