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.