NMDA receptor activation induces long-term potentiation of glycine synapses.
Of the fast ionotropic synapses, glycinergic synapses are the least well understood, but are vital for the maintenance of inhibitory signaling in the brain and spinal cord. Glycinergic signaling comprises half of the inhibitory signaling in the spinal cord, and glycinergic synapses are likely to reg...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0222066 |
| _version_ | 1818966418078564352 |
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| author | Michelle L Kloc Bruno Pradier Anda M Chirila Julie A Kauer |
| author_facet | Michelle L Kloc Bruno Pradier Anda M Chirila Julie A Kauer |
| author_sort | Michelle L Kloc |
| collection | DOAJ |
| description | Of the fast ionotropic synapses, glycinergic synapses are the least well understood, but are vital for the maintenance of inhibitory signaling in the brain and spinal cord. Glycinergic signaling comprises half of the inhibitory signaling in the spinal cord, and glycinergic synapses are likely to regulate local nociceptive processing as well as the transmission to the brain of peripheral nociceptive information. Here we have investigated the rapid and prolonged potentiation of glycinergic synapses in the superficial dorsal horn of young male and female mice after brief activation of NMDA receptors (NMDARs). Glycinergic inhibitory postsynaptic currents (IPSCs) evoked with lamina II-III stimulation in identified GABAergic neurons in lamina II were potentiated by bath-applied Zn2+ and were depressed by the prostaglandin PGE2, consistent with the presence of both GlyRα1- and GlyRα3-containing receptors. NMDA application rapidly potentiated synaptic glycinergic currents. Whole-cell currents evoked by exogenous glycine were also readily potentiated by NMDA, indicating that the potentiation results from altered numbers or conductance of postsynaptic glycine receptors. Repetitive depolarization alone of the postsynaptic GABAergic neuron also potentiated glycinergic synapses, and intracellular EGTA prevented both NMDA-induced and depolarization-induced potentiation of glycinergic IPSCs. Optogenetic activation of trpv1 lineage afferents also triggered NMDAR-dependent potentiation of glycinergic synapses. Our results suggest that during peripheral injury or inflammation, nociceptor firing during injury is likely to potentiate glycinergic synapses on GABAergic neurons. This disinhibition mechanism may be engaged rapidly, altering dorsal horn circuitry to promote the transmission of nociceptive information to the brain. |
| first_indexed | 2024-12-20T13:32:35Z |
| format | Article |
| id | doaj.art-7d5fb1c21bed4a2995567e3c71ab1e2a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T13:32:35Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-7d5fb1c21bed4a2995567e3c71ab1e2a2022-12-21T19:39:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01149e022206610.1371/journal.pone.0222066NMDA receptor activation induces long-term potentiation of glycine synapses.Michelle L KlocBruno PradierAnda M ChirilaJulie A KauerOf the fast ionotropic synapses, glycinergic synapses are the least well understood, but are vital for the maintenance of inhibitory signaling in the brain and spinal cord. Glycinergic signaling comprises half of the inhibitory signaling in the spinal cord, and glycinergic synapses are likely to regulate local nociceptive processing as well as the transmission to the brain of peripheral nociceptive information. Here we have investigated the rapid and prolonged potentiation of glycinergic synapses in the superficial dorsal horn of young male and female mice after brief activation of NMDA receptors (NMDARs). Glycinergic inhibitory postsynaptic currents (IPSCs) evoked with lamina II-III stimulation in identified GABAergic neurons in lamina II were potentiated by bath-applied Zn2+ and were depressed by the prostaglandin PGE2, consistent with the presence of both GlyRα1- and GlyRα3-containing receptors. NMDA application rapidly potentiated synaptic glycinergic currents. Whole-cell currents evoked by exogenous glycine were also readily potentiated by NMDA, indicating that the potentiation results from altered numbers or conductance of postsynaptic glycine receptors. Repetitive depolarization alone of the postsynaptic GABAergic neuron also potentiated glycinergic synapses, and intracellular EGTA prevented both NMDA-induced and depolarization-induced potentiation of glycinergic IPSCs. Optogenetic activation of trpv1 lineage afferents also triggered NMDAR-dependent potentiation of glycinergic synapses. Our results suggest that during peripheral injury or inflammation, nociceptor firing during injury is likely to potentiate glycinergic synapses on GABAergic neurons. This disinhibition mechanism may be engaged rapidly, altering dorsal horn circuitry to promote the transmission of nociceptive information to the brain.https://doi.org/10.1371/journal.pone.0222066 |
| spellingShingle | Michelle L Kloc Bruno Pradier Anda M Chirila Julie A Kauer NMDA receptor activation induces long-term potentiation of glycine synapses. PLoS ONE |
| title | NMDA receptor activation induces long-term potentiation of glycine synapses. |
| title_full | NMDA receptor activation induces long-term potentiation of glycine synapses. |
| title_fullStr | NMDA receptor activation induces long-term potentiation of glycine synapses. |
| title_full_unstemmed | NMDA receptor activation induces long-term potentiation of glycine synapses. |
| title_short | NMDA receptor activation induces long-term potentiation of glycine synapses. |
| title_sort | nmda receptor activation induces long term potentiation of glycine synapses |
| url | https://doi.org/10.1371/journal.pone.0222066 |
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