Afferent convergence to a shared population of interneuron AMPA receptors
Abstract Precise alignment of pre- and postsynaptic elements optimizes the activation of glutamate receptors at excitatory synapses. Nonetheless, glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. To uncover the extrasyna...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-38854-2 |
| _version_ | 1827933261802766336 |
|---|---|
| author | Reagan L. Pennock Luke T. Coddington Xiaohui Yan Linda Overstreet-Wadiche Jacques I. Wadiche |
| author_facet | Reagan L. Pennock Luke T. Coddington Xiaohui Yan Linda Overstreet-Wadiche Jacques I. Wadiche |
| author_sort | Reagan L. Pennock |
| collection | DOAJ |
| description | Abstract Precise alignment of pre- and postsynaptic elements optimizes the activation of glutamate receptors at excitatory synapses. Nonetheless, glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. To uncover the extrasynaptic actions of glutamate, we localized AMPA receptors (AMPARs) mediating spillover transmission between climbing fibers and molecular layer interneurons in the cerebellar cortex. We found that climbing fiber spillover generates calcium transients mediated by Ca2+-permeable AMPARs at parallel fiber synapses. Spillover occludes parallel fiber synaptic currents, indicating that separate, independently regulated afferent pathways converge onto a common pool of AMPARs. Together these findings demonstrate a circuit motif wherein glutamate ‘spill-in’ from an unconnected afferent pathway co-opts synaptic receptors, allowing activation of postsynaptic AMPARs even when canonical glutamate release is suppressed. |
| first_indexed | 2024-03-13T07:22:20Z |
| format | Article |
| id | doaj.art-7ae40411316e4b6b8cb2ac22171ce8fa |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T07:22:20Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-7ae40411316e4b6b8cb2ac22171ce8fa2023-06-04T11:33:41ZengNature PortfolioNature Communications2041-17232023-05-0114111210.1038/s41467-023-38854-2Afferent convergence to a shared population of interneuron AMPA receptorsReagan L. Pennock0Luke T. Coddington1Xiaohui Yan2Linda Overstreet-Wadiche3Jacques I. Wadiche4Department of Neurobiology, University of Alabama at BirminghamDepartment of Neurobiology, University of Alabama at BirminghamDepartment of Neurobiology, University of Alabama at BirminghamDepartment of Neurobiology, University of Alabama at BirminghamDepartment of Neurobiology, University of Alabama at BirminghamAbstract Precise alignment of pre- and postsynaptic elements optimizes the activation of glutamate receptors at excitatory synapses. Nonetheless, glutamate that diffuses out of the synaptic cleft can have actions at distant receptors, a mode of transmission called spillover. To uncover the extrasynaptic actions of glutamate, we localized AMPA receptors (AMPARs) mediating spillover transmission between climbing fibers and molecular layer interneurons in the cerebellar cortex. We found that climbing fiber spillover generates calcium transients mediated by Ca2+-permeable AMPARs at parallel fiber synapses. Spillover occludes parallel fiber synaptic currents, indicating that separate, independently regulated afferent pathways converge onto a common pool of AMPARs. Together these findings demonstrate a circuit motif wherein glutamate ‘spill-in’ from an unconnected afferent pathway co-opts synaptic receptors, allowing activation of postsynaptic AMPARs even when canonical glutamate release is suppressed.https://doi.org/10.1038/s41467-023-38854-2 |
| spellingShingle | Reagan L. Pennock Luke T. Coddington Xiaohui Yan Linda Overstreet-Wadiche Jacques I. Wadiche Afferent convergence to a shared population of interneuron AMPA receptors Nature Communications |
| title | Afferent convergence to a shared population of interneuron AMPA receptors |
| title_full | Afferent convergence to a shared population of interneuron AMPA receptors |
| title_fullStr | Afferent convergence to a shared population of interneuron AMPA receptors |
| title_full_unstemmed | Afferent convergence to a shared population of interneuron AMPA receptors |
| title_short | Afferent convergence to a shared population of interneuron AMPA receptors |
| title_sort | afferent convergence to a shared population of interneuron ampa receptors |
| url | https://doi.org/10.1038/s41467-023-38854-2 |
| work_keys_str_mv | AT reaganlpennock afferentconvergencetoasharedpopulationofinterneuronampareceptors AT luketcoddington afferentconvergencetoasharedpopulationofinterneuronampareceptors AT xiaohuiyan afferentconvergencetoasharedpopulationofinterneuronampareceptors AT lindaoverstreetwadiche afferentconvergencetoasharedpopulationofinterneuronampareceptors AT jacquesiwadiche afferentconvergencetoasharedpopulationofinterneuronampareceptors |