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NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups

N-Methyl-d-aspartate receptors (NMDARs) play diverse roles in synaptic transmission, synaptic plasticity, neuronal development and neurological diseases. In addition to their postsynaptic expression, NMDARs are also expressed in presynaptic terminals at some central synapses, and their activation mo...

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Detalles Bibliográficos
Autores principales: Oshima-Takago, Tomoko, Takago, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541344/
https://www.ncbi.nlm.nih.gov/pubmed/28747405
http://dx.doi.org/10.1098/rsob.170032
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author Oshima-Takago, Tomoko
Takago, Hideki
author_facet Oshima-Takago, Tomoko
Takago, Hideki
author_sort Oshima-Takago, Tomoko
collection PubMed
description N-Methyl-d-aspartate receptors (NMDARs) play diverse roles in synaptic transmission, synaptic plasticity, neuronal development and neurological diseases. In addition to their postsynaptic expression, NMDARs are also expressed in presynaptic terminals at some central synapses, and their activation modulates transmitter release. However, the regulatory mechanisms of NMDAR-dependent synaptic transmission remain largely unknown. In the present study, we demonstrated that activation of NMDARs in a nerve terminal at a central glutamatergic synapse inhibits presynaptic Ca(2+) currents (I(Ca)) in a GluN2C/2D subunit-dependent manner, thereby decreasing nerve-evoked excitatory postsynaptic currents. Neither presynaptically loaded fast Ca(2+) chelator BAPTA nor non-hydrolysable GTP analogue GTPγS affected NMDAR-mediated I(Ca) inhibition. In the presence of a glutamate uptake blocker, the decline in I(Ca) amplitude evoked by repetitive depolarizing pulses at 20 Hz was attenuated by an NMDAR competitive antagonist, suggesting that endogenous glutamate has a potential to activate presynaptic NMDARs. Moreover, NMDA-induced inward currents at a negative holding potential (−80 mV) were abolished by intra-terminal loading of the NMDAR open channel blocker MK-801, indicating functional expression of presynaptic NMDARs. We conclude that presynaptic NMDARs can attenuate glutamate release by inhibiting voltage-gated Ca(2+) channels at a relay synapse in the immature rat auditory brainstem.
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spelling pubmed-55413442017-08-08 NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups Oshima-Takago, Tomoko Takago, Hideki Open Biol Research N-Methyl-d-aspartate receptors (NMDARs) play diverse roles in synaptic transmission, synaptic plasticity, neuronal development and neurological diseases. In addition to their postsynaptic expression, NMDARs are also expressed in presynaptic terminals at some central synapses, and their activation modulates transmitter release. However, the regulatory mechanisms of NMDAR-dependent synaptic transmission remain largely unknown. In the present study, we demonstrated that activation of NMDARs in a nerve terminal at a central glutamatergic synapse inhibits presynaptic Ca(2+) currents (I(Ca)) in a GluN2C/2D subunit-dependent manner, thereby decreasing nerve-evoked excitatory postsynaptic currents. Neither presynaptically loaded fast Ca(2+) chelator BAPTA nor non-hydrolysable GTP analogue GTPγS affected NMDAR-mediated I(Ca) inhibition. In the presence of a glutamate uptake blocker, the decline in I(Ca) amplitude evoked by repetitive depolarizing pulses at 20 Hz was attenuated by an NMDAR competitive antagonist, suggesting that endogenous glutamate has a potential to activate presynaptic NMDARs. Moreover, NMDA-induced inward currents at a negative holding potential (−80 mV) were abolished by intra-terminal loading of the NMDAR open channel blocker MK-801, indicating functional expression of presynaptic NMDARs. We conclude that presynaptic NMDARs can attenuate glutamate release by inhibiting voltage-gated Ca(2+) channels at a relay synapse in the immature rat auditory brainstem. The Royal Society 2017-07-26 /pmc/articles/PMC5541344/ /pubmed/28747405 http://dx.doi.org/10.1098/rsob.170032 Text en © 2017 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Oshima-Takago, Tomoko
Takago, Hideki
NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups
title NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups
title_full NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups
title_fullStr NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups
title_full_unstemmed NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups
title_short NMDA receptor-dependent presynaptic inhibition at the calyx of Held synapse of rat pups
title_sort nmda receptor-dependent presynaptic inhibition at the calyx of held synapse of rat pups
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541344/
https://www.ncbi.nlm.nih.gov/pubmed/28747405
http://dx.doi.org/10.1098/rsob.170032
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