Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development
Abstract NMDA receptors are heteromeric complexes that contribute to excitatory synaptic transmission and plasticity. The presence of specific variants of GluN2 subunits in these complexes enables diversity in NMDA receptor function and regulation. At brain synapses, there is a switch from slow GluN...
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | Molecular Brain |
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| Online Access: | http://link.springer.com/article/10.1186/s13041-020-00566-9 |
| _version_ | 1818109047481565184 |
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| author | Hadir Mahmoud Newton Martin Michael E. Hildebrand |
| author_facet | Hadir Mahmoud Newton Martin Michael E. Hildebrand |
| author_sort | Hadir Mahmoud |
| collection | DOAJ |
| description | Abstract NMDA receptors are heteromeric complexes that contribute to excitatory synaptic transmission and plasticity. The presence of specific variants of GluN2 subunits in these complexes enables diversity in NMDA receptor function and regulation. At brain synapses, there is a switch from slow GluN2B-mediated NMDA receptors to faster GluN2A-dominated NMDA receptors as well as an increase in the ratio of AMPA to NMDA receptors during early postnatal development. This glutamate receptor switch is observed across brain regions and is critical for synaptic maturation, circuit development, and associative learning. However, whether a similar receptor subunit switch occurs within pain processing neurons in the developing spinal cord remains untested. To investigate this, we performed whole-cell patch clamp recordings of excitatory synaptic responses from lamina II dorsal horn neurons of one to three week-old rats. We found that GluN2B and GluN2A both prominently contribute to NMDA receptor responses at neonatal lamina II synapses, with a small contribution from GluN2D as well. Surprisingly, we found that this molecular identity of NMDA receptor responses as well as the relative contribution of AMPA receptors versus NMDA receptors did not change at lamina II synapses across early postnatal development (P7 to P21). The lack of a developmental switch and persistence of slow-decaying GluN2B- and GluN2D-mediated synaptic responses throughout neuronal maturation in the dorsal horn has implications for understanding both the regulation of synaptic glutamatergic receptors as well as spinal mechanisms of pain processing. |
| first_indexed | 2024-12-11T02:25:02Z |
| format | Article |
| id | doaj.art-09df03cb10f6464a8178def90c51bb41 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-11T02:25:02Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-09df03cb10f6464a8178def90c51bb412022-12-22T01:23:56ZengBMCMolecular Brain1756-66062020-03-011311710.1186/s13041-020-00566-9Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal developmentHadir Mahmoud0Newton Martin1Michael E. Hildebrand2Department of Neuroscience, Carleton UniversityDepartment of Neuroscience, Carleton UniversityDepartment of Neuroscience, Carleton UniversityAbstract NMDA receptors are heteromeric complexes that contribute to excitatory synaptic transmission and plasticity. The presence of specific variants of GluN2 subunits in these complexes enables diversity in NMDA receptor function and regulation. At brain synapses, there is a switch from slow GluN2B-mediated NMDA receptors to faster GluN2A-dominated NMDA receptors as well as an increase in the ratio of AMPA to NMDA receptors during early postnatal development. This glutamate receptor switch is observed across brain regions and is critical for synaptic maturation, circuit development, and associative learning. However, whether a similar receptor subunit switch occurs within pain processing neurons in the developing spinal cord remains untested. To investigate this, we performed whole-cell patch clamp recordings of excitatory synaptic responses from lamina II dorsal horn neurons of one to three week-old rats. We found that GluN2B and GluN2A both prominently contribute to NMDA receptor responses at neonatal lamina II synapses, with a small contribution from GluN2D as well. Surprisingly, we found that this molecular identity of NMDA receptor responses as well as the relative contribution of AMPA receptors versus NMDA receptors did not change at lamina II synapses across early postnatal development (P7 to P21). The lack of a developmental switch and persistence of slow-decaying GluN2B- and GluN2D-mediated synaptic responses throughout neuronal maturation in the dorsal horn has implications for understanding both the regulation of synaptic glutamatergic receptors as well as spinal mechanisms of pain processing.http://link.springer.com/article/10.1186/s13041-020-00566-9Spinal cordDorsal hornLamina IISynapseNMDA receptorGluN2A |
| spellingShingle | Hadir Mahmoud Newton Martin Michael E. Hildebrand Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development Molecular Brain Spinal cord Dorsal horn Lamina II Synapse NMDA receptor GluN2A |
| title | Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development |
| title_full | Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development |
| title_fullStr | Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development |
| title_full_unstemmed | Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development |
| title_short | Conserved contributions of NMDA receptor subtypes to synaptic responses in lamina II spinal neurons across early postnatal development |
| title_sort | conserved contributions of nmda receptor subtypes to synaptic responses in lamina ii spinal neurons across early postnatal development |
| topic | Spinal cord Dorsal horn Lamina II Synapse NMDA receptor GluN2A |
| url | http://link.springer.com/article/10.1186/s13041-020-00566-9 |
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