Metabotropic glutamate receptor mediated long-term depression in developing hippocampus

Academic Article

Abstract

  • The effects of bath application of the metabotropic glutamate receptor (mGluR) agonist IS,3R- l-aminocyclopentane- 1,3-dicarboxylic acid (ACPD, 10 μM) were studied at the Schaffer collateral-CA 1 synapse in hippocampal slices from rats of 8-33 days postnatal age. In immature animals (8-12 days) ACPD induced a biphasic response characterized by an acute decrease in field EPSP slope (κ50-60% of baseline) in the presence of the agonist, followed by long-term depression (LTD, κ 75-80% of baseline) after washout. In animals older than 20 days, ACPD induced a slow onset potentiation or minimal change. Both the acute depression and LTD were blocked by the mGluR antagonist α- methyl-4-carboxyphenyl glycine (MCPG). ACPD-induced LTD was blocked by the N- methyI-D-aspartate receptor (NMDAR) antagonists D(-)-2-amino-5 phosphopentanoic acid (AP5) and dizocilpine maleate (MK-801), and by ethanol. Glutamic pyruvic transaminase, an enzyme that selectively metabolizes endogenous extracellular glutamate, also blocked LTD suggesting that the requisite NMDA currents were tonically activated by extracellular rather than synaptically released glutamate. ACPD-induced LTD was blocked by staurosporine, indicating a requirement for serine threonine kinase activation, and was unaffected by the L-type voltage sensitive calcium channel blocker nitrendipine and the A1 adenosine receptor antagonist 8- cyclopentyl-l,3-dimethylxanthine (CPT). Because mGluR-mediated LTD was observed only in immature CAI, mGluRs may play a role in hippocampal development, perhaps by contributing to synapse pruning in a temporally restricted fashion.
  • Authors

    Published In

  • Neuropharmacology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Overstreet LS; Pasternak JF; Colley PA; Slater NT; Trommer BL
  • Start Page

  • 831
  • End Page

  • 844
  • Volume

  • 36
  • Issue

  • 6