GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels

N-methyl-d-aspartate receptors (NMDARs) play a pivotal role in synaptic plasticity. While the functional role of post-synaptic NMDARs is well established, pre-synaptic NMDAR (pre-NMDAR) function is largely unexplored. Different pre-NMDAR subunit populations are documented at synapses, suggesting tha...

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Main Authors: Schmidt, CC, Tong, R, Emptage, NJ
Format: Journal article
Language:English
Published: The Royal Society 2024
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author Schmidt, CC
Tong, R
Emptage, NJ
author_facet Schmidt, CC
Tong, R
Emptage, NJ
author_sort Schmidt, CC
collection OXFORD
description N-methyl-d-aspartate receptors (NMDARs) play a pivotal role in synaptic plasticity. While the functional role of post-synaptic NMDARs is well established, pre-synaptic NMDAR (pre-NMDAR) function is largely unexplored. Different pre-NMDAR subunit populations are documented at synapses, suggesting that subunit composition influences neuronal transmission. Here, we used electrophysiological recordings at Schaffer collateral-CA1 synapses partnered with Ca2+ imaging and glutamate uncaging at boutons of CA3 pyramidal neurones to reveal two populations of pre-NMDARs that contain either the GluN2A or GluN2B subunit. Activation of the GluN2B population decreases action potential-evoked Ca2+ influx via modulation of small-conductance Ca2+-activated K+ channels, while activation of the GluN2A population does the opposite. Critically, the level of functional expression of the subunits is subject to homeostatic regulation, bidirectionally affecting short-term facilitation, thus providing a capacity for a fine adjustment of information transfer. This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
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spelling oxford-uuid:75254dbb-3e3f-4035-bf06-62d6e93026d92024-06-10T20:04:48ZGluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channelsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:75254dbb-3e3f-4035-bf06-62d6e93026d9EnglishJisc Publications RouterThe Royal Society2024Schmidt, CCTong, REmptage, NJN-methyl-d-aspartate receptors (NMDARs) play a pivotal role in synaptic plasticity. While the functional role of post-synaptic NMDARs is well established, pre-synaptic NMDAR (pre-NMDAR) function is largely unexplored. Different pre-NMDAR subunit populations are documented at synapses, suggesting that subunit composition influences neuronal transmission. Here, we used electrophysiological recordings at Schaffer collateral-CA1 synapses partnered with Ca2+ imaging and glutamate uncaging at boutons of CA3 pyramidal neurones to reveal two populations of pre-NMDARs that contain either the GluN2A or GluN2B subunit. Activation of the GluN2B population decreases action potential-evoked Ca2+ influx via modulation of small-conductance Ca2+-activated K+ channels, while activation of the GluN2A population does the opposite. Critically, the level of functional expression of the subunits is subject to homeostatic regulation, bidirectionally affecting short-term facilitation, thus providing a capacity for a fine adjustment of information transfer. This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
spellingShingle Schmidt, CC
Tong, R
Emptage, NJ
GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels
title GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels
title_full GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels
title_fullStr GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels
title_full_unstemmed GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels
title_short GluN2A- and GluN2B-containing pre-synaptic N -methyl- d -aspartate receptors differentially regulate action potential-evoked Ca 2+ influx via modulation of SK channels
title_sort glun2a and glun2b containing pre synaptic n methyl d aspartate receptors differentially regulate action potential evoked ca 2 influx via modulation of sk channels
work_keys_str_mv AT schmidtcc glun2aandglun2bcontainingpresynapticnmethyldaspartatereceptorsdifferentiallyregulateactionpotentialevokedca2influxviamodulationofskchannels
AT tongr glun2aandglun2bcontainingpresynapticnmethyldaspartatereceptorsdifferentiallyregulateactionpotentialevokedca2influxviamodulationofskchannels
AT emptagenj glun2aandglun2bcontainingpresynapticnmethyldaspartatereceptorsdifferentiallyregulateactionpotentialevokedca2influxviamodulationofskchannels