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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2017
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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. |
format | Online Article Text |
id | pubmed-5541344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
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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