Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors
Synaptic NMDA receptors (NMDARs) are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs) recruit shaft NMDARs...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-05-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124712000927 |
| _version_ | 1811297669821235200 |
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| author | Yu-Wei Wu Sergei Grebenyuk Thomas J. McHugh Dmitri A. Rusakov Alexey Semyanov |
| author_facet | Yu-Wei Wu Sergei Grebenyuk Thomas J. McHugh Dmitri A. Rusakov Alexey Semyanov |
| author_sort | Yu-Wei Wu |
| collection | DOAJ |
| description | Synaptic NMDA receptors (NMDARs) are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs) recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh) of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation. |
| first_indexed | 2024-04-13T06:07:57Z |
| format | Article |
| id | doaj.art-801c39740c35445dad6c7c705778997e |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-13T06:07:57Z |
| publishDate | 2012-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-801c39740c35445dad6c7c705778997e2022-12-22T02:59:11ZengElsevierCell Reports2211-12472012-05-011549550510.1016/j.celrep.2012.03.007Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA ReceptorsYu-Wei Wu0Sergei Grebenyuk1Thomas J. McHugh2Dmitri A. Rusakov3Alexey Semyanov4RIKEN Brain Science Institute, Wako, Saitama 351-0198, JapanRIKEN Brain Science Institute, Wako, Saitama 351-0198, JapanRIKEN Brain Science Institute, Wako, Saitama 351-0198, JapanUCL Institute of Neurology, University College London, London WC1N 3BG, UKRIKEN Brain Science Institute, Wako, Saitama 351-0198, JapanSynaptic NMDA receptors (NMDARs) are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs) recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh) of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.http://www.sciencedirect.com/science/article/pii/S2211124712000927 |
| spellingShingle | Yu-Wei Wu Sergei Grebenyuk Thomas J. McHugh Dmitri A. Rusakov Alexey Semyanov Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors Cell Reports |
| title | Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors |
| title_full | Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors |
| title_fullStr | Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors |
| title_full_unstemmed | Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors |
| title_short | Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors |
| title_sort | backpropagating action potentials enable detection of extrasynaptic glutamate by nmda receptors |
| url | http://www.sciencedirect.com/science/article/pii/S2211124712000927 |
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