Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space
Background: We recently reported sex-dependent impairment in cognitive functions in male and female mice exposed for 24 h, 48 h or 15 days to 2G hypergravity (HG). Methods: In the present study, we investigated brain functional correlates by analyzing synaptic activity and plasticity in the CA1 area...
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MDPI AG
2025-07-01
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| author | Mathilde Wullen Valentine Bouet Thomas Freret Jean-Marie Billard |
| author_facet | Mathilde Wullen Valentine Bouet Thomas Freret Jean-Marie Billard |
| author_sort | Mathilde Wullen |
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| description | Background: We recently reported sex-dependent impairment in cognitive functions in male and female mice exposed for 24 h, 48 h or 15 days to 2G hypergravity (HG). Methods: In the present study, we investigated brain functional correlates by analyzing synaptic activity and plasticity in the CA1 area of the hippocampus in both genders of mice previously exposed to 2G for the same duration. This was assessed by electrophysiological extracellular recordings in ex vivo slice preparations. Results: Basal synaptic transmission and glutamate release were unchanged regardless of HG duration. However, plasticity was altered in a sex- and time-specific manner. In males, long-term potentiation (LTP) induced by strong high-frequency stimulation and NMDA receptor (NMDAr) activation was reduced by 26% after 24 h of exposure but recovered at later timepoints. This deficit was reversed by D-serine or glycine, suggesting decreased activation at the NMDAr co-agonist site. In females, LTP deficits (23%) were found only after 15 days following mild theta burst stimulation and were not reversed by D-serine. Long-term depression (LTD) was unaffected in both sexes. Conclusions: This study highlights, for the first time, sex-dependent divergence in the CA1 hippocampal plasticity timeline following 2G exposure. The synaptic changes depend on exposure duration and the stimulation protocol and could underlie the previously observed cognitive deficits. |
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| institution | Kabale University |
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| language | English |
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| spelling | doaj-art-fa9ec7871c7c4e5b90e2b79edef0de5e2025-08-20T03:35:58ZengMDPI AGCells2073-44092025-07-011415118610.3390/cells14151186Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in SpaceMathilde Wullen0Valentine Bouet1Thomas Freret2Jean-Marie Billard3Campus Horowitz, Normandie Université, UNICAEN, INSERM, CYCERON, CHU Caen, COMETE UMR 1075, 14000 Caen, FranceCampus Horowitz, Normandie Université, UNICAEN, INSERM, CYCERON, CHU Caen, COMETE UMR 1075, 14000 Caen, FranceCampus Horowitz, Normandie Université, UNICAEN, INSERM, CYCERON, CHU Caen, COMETE UMR 1075, 14000 Caen, FranceCampus Horowitz, Normandie Université, UNICAEN, INSERM, CYCERON, CHU Caen, COMETE UMR 1075, 14000 Caen, FranceBackground: We recently reported sex-dependent impairment in cognitive functions in male and female mice exposed for 24 h, 48 h or 15 days to 2G hypergravity (HG). Methods: In the present study, we investigated brain functional correlates by analyzing synaptic activity and plasticity in the CA1 area of the hippocampus in both genders of mice previously exposed to 2G for the same duration. This was assessed by electrophysiological extracellular recordings in ex vivo slice preparations. Results: Basal synaptic transmission and glutamate release were unchanged regardless of HG duration. However, plasticity was altered in a sex- and time-specific manner. In males, long-term potentiation (LTP) induced by strong high-frequency stimulation and NMDA receptor (NMDAr) activation was reduced by 26% after 24 h of exposure but recovered at later timepoints. This deficit was reversed by D-serine or glycine, suggesting decreased activation at the NMDAr co-agonist site. In females, LTP deficits (23%) were found only after 15 days following mild theta burst stimulation and were not reversed by D-serine. Long-term depression (LTD) was unaffected in both sexes. Conclusions: This study highlights, for the first time, sex-dependent divergence in the CA1 hippocampal plasticity timeline following 2G exposure. The synaptic changes depend on exposure duration and the stimulation protocol and could underlie the previously observed cognitive deficits.https://www.mdpi.com/2073-4409/14/15/1186hypergravityelectrophysiologylong term potentiationNMDA receptorlong term depressionmemory |
| spellingShingle | Mathilde Wullen Valentine Bouet Thomas Freret Jean-Marie Billard Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space Cells hypergravity electrophysiology long term potentiation NMDA receptor long term depression memory |
| title | Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space |
| title_full | Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space |
| title_fullStr | Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space |
| title_full_unstemmed | Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space |
| title_short | Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space |
| title_sort | sexual dimorphism of synaptic plasticity changes in ca1 hippocampal networks in hypergravity exposed mice new insights for cognition in space |
| topic | hypergravity electrophysiology long term potentiation NMDA receptor long term depression memory |
| url | https://www.mdpi.com/2073-4409/14/15/1186 |
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