ArcKR expression modifies potentiation in environmental enriched conditions.
Several studies have shown that increasing the enrichment of the housing environment of rodents leads to enhanced synaptic plasticity and improved learning (Sale et al. , 2014; Fischer, 2016; Ohline & Abraham, 2019; Cooper & Frenguelli, 2021). In a recent study, LTP was markedly increased at SC-CA1 synapses in hippocampus obtained from mice exposed to environmental enrichment for 5 months, with no change in basal synaptic transmission. In these mice Arc protein expression was significantly reduced (Privitera et al. , 2020). Here we have investigated whether environmental enrichment has differential effects on LTP magnitude in ArcKR compared to WT mice. Firstly, LTP was induced in standard-housed mice using 3 bursts of TBS as in (Privitera et al. , 2020). No significant changes in LTP were observed after an hour between WT and ArcKR mice (Fig 4A, C). Before repeating the experiment in environmentally-enriched mice, we investigated if the enrichment induced any changes in basal synaptic transmission between the genotypes. There were no significant changes in the stimulus input-output relationship (Fig 4D) or the degree of paired-pulse facilitation (Fig 4E). Although there was no significant difference in LTP magnitude (induced with 3 burst of TBS, Fig 4F, G) between the genotypes, there was a significant reduction in the ratio of LTP to short-term potentiation (STP; Fig 4H). This measurement removes the variance in absolute LTP from across slices. This change in ratio reflects a decline in potentiation after STP in ArcKR, while potentiation was more stable for WT following STP (Fig 4F). This difference in LTP/STP ratio is not a consequence of differences in synaptic activation between the synapses, as the slope of baseline fEPSPs was not significantly different (p = 0.228, Z = -1.206, U = 83, Mann Whitney) between the genotypes. No such difference was observed in the ratio of LTP/STP in standard housed ArcKR mice (Fig 4C) and thus appears to be a consequence of the environmental enrichment.