Separate ionotropic and metabotropic glutamate receptor functions in depotentiation vs. LTP: A distinct role for group1 mGluR subtypes and NMDARs

Amira Latif-Hernandez, Enrico Faldini, Tariq Ahmed, Detlef Balschun

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7 Citations (Scopus)

Abstract

Depotentiation (DP) is a mechanism by which synapses that have recently undergone long-term potentiation (LTP) can reverse their synaptic strengthening within a short time-window after LTP induction. Group 1 metabotropic glutamate receptors (mGluRs) were shown to be involved in different forms of LTP and long-term depression (LTD), but little is known about their roles in DP. Here, we generated DP by applying low-frequency stimulation (LFS) at 5 Hz after LTP had been induced by a single train of theta-burst-stimulation (TBS). While application of LFS for 2 min (DP2′) generated only a short-lasting DP that was independent of the activation of N-methyl-D-aspartate receptors (NMDARs) and group 1 mGluRs, LFS given for 8 min (DP8′) induced a robust DP that was maintained for at least 2 h. This strong form of DP was contingent on NMDAR activation. Interestingly, DP8′ appears to include a metabotropic NMDAR function because it was blocked by the competitive NMDAR antagonist D-AP5 but not by the use-dependent inhibitor MK-801 or high Mg2+. Furthermore, DP80 was enhanced by application of the mGluR1 antagonist (YM 298198, 1 μM). The mGluR5 antagonist 2-Methyl- 6(phenylethynyl) pyridine (MPEP, 40 μM), in contrast, failed to affect it. The induction of LTP, in turn, was NMDAR dependent (as tested with D-AP5), and blocked by MPEP but not by YM 298198. These results indicate a functional dissociation of mGluR1 and mGluR5 in two related and consecutively induced types of NMDAR-dependent synaptic plasticity (LTP → DP) with far-reaching consequences for their role in plasticity and learning under normal and pathological conditions.

Original languageEnglish
Article number252
JournalFrontiers in Cellular Neuroscience
Volume10
Issue numberNOV2016
DOIs
Publication statusPublished - 7 Nov 2016
Externally publishedYes

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Keywords

  • Depotentiation
  • Long-term potentiation
  • Metabotropic glutamate receptors
  • Metabotropic NMDA receptor function
  • Mouse hippocampus

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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