Separate Ionotropic and Metabotropic Glutamate Receptor Functions in Depotentiation vs. LTP: A Distinct Role for Group1 mGluR Subtypes and NMDARs

• Published in: Frontiers in cellular neuroscience Vol. 10; p. 252
• Main Authors: Latif-Hernandez, Amira, Faldini, Enrico, Ahmed, Tariq, Balschun, Detlef
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 07.11.2016; Frontiers Media S.A
• Subjects: Dizocilpine; Glutamic acid receptors (ionotropic); Glutamic acid receptors (metabotropic); Investigations; Kinases; Laboratories; Long-term depression; Long-term potentiation; Magnesium; Memory; N-Methyl-D-aspartic acid receptors; Neuroscience; Proteins; Signal transduction; Synaptic plasticity; depotentiation; metabotropic NMDA receptor function; metabotropic glutamate receptors; mouse hippocampus; long-term potentiation
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2016.00252

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 -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 Mg . Furthermore, DP8' 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.