Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses
The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic and sensory information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecti...
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eLife Sciences Publications Ltd
2024-11-01
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| author | Irene Martínez-Gallego Heriberto Coatl-Cuaya Antonio Rodriguez-Moreno |
| author_facet | Irene Martínez-Gallego Heriberto Coatl-Cuaya Antonio Rodriguez-Moreno |
| author_sort | Irene Martínez-Gallego |
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| description | The entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic and sensory information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells of the DG play a role in memory encoding and information processing and are deeply affected in humans suffering Alzheimer’s disease and temporal lobe epilepsy, contributing to the dysfunctions found in these pathologies. The plasticity of these synapses is not well known yet, as are not known the forms of long-term depression (LTD) existing at those connections. We investigated whether spike timing-dependent long-term depression (t-LTD) exists at these two different EC-DG synaptic connections in mice, and whether they have different action mechanisms. We have found two different forms of t-LTD, at LPP- and MPP-GC synapses and characterised their cellular and intracellular mechanistic requirements. We found that both forms of t-LTD are expressed presynaptically and that whereas t-LTD at LPP-GC synapses does not require NMDAR, t-LTD at MPP-GC synapses requires ionotropic NMDAR containing GluN2A subunits. The two forms of t-LTD require different group I mGluR, mGluR5 LPP-GC synapses and mGluR1 MPP-GC synapses. In addition, both forms of t-LTD require postsynaptic calcium, eCB synthesis, CB1R, astrocyte activity, and glutamate released by astrocytes. Thus, we discovered two novel forms of t-LTD that require astrocytes at EC-GC synapses. |
| format | Article |
| id | doaj-art-9e40bff419564d8cb146ed8685b0bcd9 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2024-11-01 |
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| spelling | doaj-art-9e40bff419564d8cb146ed8685b0bcd92024-11-14T17:35:32ZengeLife Sciences Publications LtdeLife2050-084X2024-11-011310.7554/eLife.98031Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapsesIrene Martínez-Gallego0Heriberto Coatl-Cuaya1Antonio Rodriguez-Moreno2https://orcid.org/0000-0002-8078-6175Laboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Sevilla, SpainLaboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Sevilla, SpainLaboratory of Cellular Neuroscience and Plasticity, Department of Physiology, Anatomy and Cell Biology, Universidad Pablo de Olavide, Sevilla, SpainThe entorhinal cortex (EC) connects to the hippocampus sending different information from cortical areas that is first processed at the dentate gyrus (DG) including spatial, limbic and sensory information. Excitatory afferents from lateral (LPP) and medial (MPP) perforant pathways of the EC connecting to granule cells of the DG play a role in memory encoding and information processing and are deeply affected in humans suffering Alzheimer’s disease and temporal lobe epilepsy, contributing to the dysfunctions found in these pathologies. The plasticity of these synapses is not well known yet, as are not known the forms of long-term depression (LTD) existing at those connections. We investigated whether spike timing-dependent long-term depression (t-LTD) exists at these two different EC-DG synaptic connections in mice, and whether they have different action mechanisms. We have found two different forms of t-LTD, at LPP- and MPP-GC synapses and characterised their cellular and intracellular mechanistic requirements. We found that both forms of t-LTD are expressed presynaptically and that whereas t-LTD at LPP-GC synapses does not require NMDAR, t-LTD at MPP-GC synapses requires ionotropic NMDAR containing GluN2A subunits. The two forms of t-LTD require different group I mGluR, mGluR5 LPP-GC synapses and mGluR1 MPP-GC synapses. In addition, both forms of t-LTD require postsynaptic calcium, eCB synthesis, CB1R, astrocyte activity, and glutamate released by astrocytes. Thus, we discovered two novel forms of t-LTD that require astrocytes at EC-GC synapses.https://elifesciences.org/articles/98031PlasticityLTDentorhinal cortexdentate gyrusastrocytesNMDARs |
| spellingShingle | Irene Martínez-Gallego Heriberto Coatl-Cuaya Antonio Rodriguez-Moreno Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses eLife Plasticity LTD entorhinal cortex dentate gyrus astrocytes NMDARs |
| title | Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses |
| title_full | Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses |
| title_fullStr | Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses |
| title_full_unstemmed | Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses |
| title_short | Astrocytes mediate two forms of spike timing-dependent depression at entorhinal cortex-hippocampal synapses |
| title_sort | astrocytes mediate two forms of spike timing dependent depression at entorhinal cortex hippocampal synapses |
| topic | Plasticity LTD entorhinal cortex dentate gyrus astrocytes NMDARs |
| url | https://elifesciences.org/articles/98031 |
| work_keys_str_mv | AT irenemartinezgallego astrocytesmediatetwoformsofspiketimingdependentdepressionatentorhinalcortexhippocampalsynapses AT heribertocoatlcuaya astrocytesmediatetwoformsofspiketimingdependentdepressionatentorhinalcortexhippocampalsynapses AT antoniorodriguezmoreno astrocytesmediatetwoformsofspiketimingdependentdepressionatentorhinalcortexhippocampalsynapses |