# Sexual Dimorphism of Synaptic Plasticity Changes in CA1 Hippocampal Networks in Hypergravity-Exposed Mice—New Insights for Cognition in Space

## TL;DR

This study finds that male and female mice react differently to hypergravity exposure in terms of brain plasticity, which could affect cognition in space.

## Contribution

The study reveals sex-specific differences in hippocampal plasticity changes following hypergravity exposure, a novel insight into cognitive effects in space.

## Key findings

- Males showed reduced LTP after 24 h of 2G exposure, recoverable with D-serine or glycine.
- Females exhibited LTP deficits after 15 days of 2G exposure, not reversed by D-serine.
- LTD remained unaffected in both sexes regardless of exposure duration.

## Abstract

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.