Slowly developing depression of N-methyl-D-aspartate receptor mediated responses in young rat hippocampiReport as inadecuate




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BMC Neuroscience

, 5:26

First Online: 03 August 2004Received: 10 May 2004Accepted: 03 August 2004

Abstract

BackgroundActivation of N-methyl-D-aspartate NMDA type glutamate receptors is essential in triggering various forms of synaptic plasticity. A critical issue is to what extent such plasticity involves persistent changes of glutamate receptor subtypes and many prior studies have suggested a main role for alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid AMPA receptors in mediating the effect. Our previous work in hippocampal slices revealed that, under pharmacological unblocking of NMDA receptors, both AMPA and NMDA receptor mediated responses undergo a slowly developing depression. In the present study we have further adressed this phenomenon, focusing on the contribution via NMDA receptors. Pharmacologically isolated NMDA receptor mediated excitatory postsynaptic potentials EPSPs were recorded for two independent synaptic pathways in CA1 area using perfusion with low Mg 0.1 mM to unblock NMDA receptors.

ResultsFollowing unblocking of NMDA receptors, there was a gradual decline of NMDA receptor mediated EPSPs for 2–3 hours towards a stable level of ca. 60–70 % of the maximal size. If such an experimental session was repeated twice in the same pathway with a period of NMDA receptor blockade in between, the depression attained in the first session was still evident in the second one and no further decay occurred. The persistency of the depression was also validated by comparison between pathways. It was found that the responses of a control pathway, unstimulated in the first session of receptor unblocking, behaved as novel responses when tested in association with the depressed pathway under the second session. In similar experiments, but with AP5 present during the first session, there was no subsequent difference between NMDA EPSPs.

ConclusionsOur findings show that merely evoking NMDA receptor mediated responses results in a depression which is input specific, induced via NMDA receptor activation, and is maintained for several hours through periods of receptor blockade. The similarity to key features of long-term depression and long-term potentiation suggests a possible relation to these phenomena. Additionally, a short term potentiation and decay <5 min were observed during sudden start of NMDA receptor activation supporting the idea that NMDA receptor mediated responses are highly plastic.

AbbreviationsAMPAalpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

AP5D-2-amino-5-phosphonopentanoic acid

CAcornu ammonis

CNQX6-cyano-7-nitroquinoxaline-2,3-dione

EPSPexcitatory postsynaptic potential

LTDlong-term depression

LTPlong-term potentiation

NMDAN-methyl-D-aspartate

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2202-5-26 contains supplementary material, which is available to authorized users.

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Author: Mikhail Dozmorov - Rui Li - Hui-Ping Xu - Barbro Jilderos - Holger Wigström

Source: https://link.springer.com/







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