Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine
Astrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which a...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1282841/full |
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| author | Daniela Sofia Abreu Daniela Sofia Abreu Joana I. Gomes Joana I. Gomes Filipa F. Ribeiro Filipa F. Ribeiro Maria J. Diógenes Maria J. Diógenes Ana M. Sebastião Ana M. Sebastião Sandra H. Vaz Sandra H. Vaz |
| author_facet | Daniela Sofia Abreu Daniela Sofia Abreu Joana I. Gomes Joana I. Gomes Filipa F. Ribeiro Filipa F. Ribeiro Maria J. Diógenes Maria J. Diógenes Ana M. Sebastião Ana M. Sebastião Sandra H. Vaz Sandra H. Vaz |
| author_sort | Daniela Sofia Abreu |
| collection | DOAJ |
| description | Astrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic plasticity. However, the precise impact of astrocyte-released D-serine on neuronal modulation remains insufficiently characterized. To address this, we have used the dominant negative SNARE (dnSNARE) mouse model, which selectively inhibits SNARE-dependent exocytosis from astrocytes. We recorded field excitatory postsynaptic potentials (fEPSPs) in CA3-CA1 synapses within hippocampal slices obtained from dnSNARE mice and wild-type (Wt) littermates. Our results demonstrate that hippocampal θ-burst long-term potentiation (LTP), a critical form of synaptic plasticity, is impaired in hippocampal slices from dnSNARE mice. Notably, this LTP impairment was rescued upon incubation with D-serine. To further investigate the involvement of astrocytes in D-serine-mediated mechanisms of LTP maintenance, we perfused hippocampal slices with L-serine – a substrate used by both neurons and astrocytes for D-serine production. The enhancement in LTP observed in dnSNARE mice was exclusively associated with D-serine presence, with no effects evident in the presence of L-serine. Additionally, both D- and L-serine reduced basal synaptic strength in the hippocampal slices of both Wt and dnSNARE mice. These results provide compelling evidence that distinct processes underlie the modulation of basal synaptic transmission and LTP through D-serine. Our findings underscore the pivotal contribution of astrocytes in D-serine-mediated processes that govern LTP establishment and basal transmission. This study not only provides essential insights into the intricate interplay between neurons and astrocytes but also emphasizes their collective role in shaping hippocampal synaptic function. |
| first_indexed | 2024-03-09T01:57:01Z |
| format | Article |
| id | doaj.art-88bc3662c30d41e48db116c7ad3c61d4 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-09T01:57:01Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-88bc3662c30d41e48db116c7ad3c61d42023-12-08T14:18:12ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-12-011710.3389/fncel.2023.12828411282841Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serineDaniela Sofia Abreu0Daniela Sofia Abreu1Joana I. Gomes2Joana I. Gomes3Filipa F. Ribeiro4Filipa F. Ribeiro5Maria J. Diógenes6Maria J. Diógenes7Ana M. Sebastião8Ana M. Sebastião9Sandra H. Vaz10Sandra H. Vaz11Faculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Medicina Molecular João Lobo Antunes, Universidade de Lisboa, Lisbon, PortugalFaculdade de Medicina, Instituto de Farmacologia e Neurociências, Universidade de Lisboa, Lisbon, PortugalAstrocytes, the most abundant glial cells in the central nervous system (CNS), sense synaptic activity and respond through the release of gliotransmitters, a process mediated by intracellular Ca2+ level changes and SNARE-dependent mechanisms. Ionotropic N-methyl-D-aspartate (NMDA) receptors, which are activated by glutamate along with D-serine or glycine, play a crucial role in learning, memory, and synaptic plasticity. However, the precise impact of astrocyte-released D-serine on neuronal modulation remains insufficiently characterized. To address this, we have used the dominant negative SNARE (dnSNARE) mouse model, which selectively inhibits SNARE-dependent exocytosis from astrocytes. We recorded field excitatory postsynaptic potentials (fEPSPs) in CA3-CA1 synapses within hippocampal slices obtained from dnSNARE mice and wild-type (Wt) littermates. Our results demonstrate that hippocampal θ-burst long-term potentiation (LTP), a critical form of synaptic plasticity, is impaired in hippocampal slices from dnSNARE mice. Notably, this LTP impairment was rescued upon incubation with D-serine. To further investigate the involvement of astrocytes in D-serine-mediated mechanisms of LTP maintenance, we perfused hippocampal slices with L-serine – a substrate used by both neurons and astrocytes for D-serine production. The enhancement in LTP observed in dnSNARE mice was exclusively associated with D-serine presence, with no effects evident in the presence of L-serine. Additionally, both D- and L-serine reduced basal synaptic strength in the hippocampal slices of both Wt and dnSNARE mice. These results provide compelling evidence that distinct processes underlie the modulation of basal synaptic transmission and LTP through D-serine. Our findings underscore the pivotal contribution of astrocytes in D-serine-mediated processes that govern LTP establishment and basal transmission. This study not only provides essential insights into the intricate interplay between neurons and astrocytes but also emphasizes their collective role in shaping hippocampal synaptic function.https://www.frontiersin.org/articles/10.3389/fncel.2023.1282841/fullastrocytegliotransmissiond-serinesynaptic plasticitytripartite synapse |
| spellingShingle | Daniela Sofia Abreu Daniela Sofia Abreu Joana I. Gomes Joana I. Gomes Filipa F. Ribeiro Filipa F. Ribeiro Maria J. Diógenes Maria J. Diógenes Ana M. Sebastião Ana M. Sebastião Sandra H. Vaz Sandra H. Vaz Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine Frontiers in Cellular Neuroscience astrocyte gliotransmission d-serine synaptic plasticity tripartite synapse |
| title | Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine |
| title_full | Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine |
| title_fullStr | Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine |
| title_full_unstemmed | Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine |
| title_short | Astrocytes control hippocampal synaptic plasticity through the vesicular-dependent release of D-serine |
| title_sort | astrocytes control hippocampal synaptic plasticity through the vesicular dependent release of d serine |
| topic | astrocyte gliotransmission d-serine synaptic plasticity tripartite synapse |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1282841/full |
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