Basal synaptic transmission in the hippocampus of ArcKR mice is not significantly different compared to WT mice but PP-LFS mediated LTD is significantly enhanced.
Before examining synaptic plasticity, we confirmed our previous observations (in 21–35-day old mice, Wall et al 2018) that basal synaptic transmission in the hippocampus of ArcKR mice is not significantly different from that in wildtype mice (at 2-3 months of age). There was no significant difference in the stimulus input/output relationships (Figure 1A) or in the degree of paired-pulse facilitation at Schaffer collateral-CA1 (SC-CA1) synapses between ArcKR and WT mice (Figure 1B). In corroboration of these findings, there was no significant difference in the expression of Arc protein in hippocampal lysates obtained from WT and ArcKR mice (at 2-3 months of age, Figure 1C). We have previously shown that mGluR-mediated long-term depression (LTD) induced with the group 1 (G1)-mGluR agonist DHPG is enhanced in the hippocampus obtained from juvenile ArcKR mice (Wall et al. , 2018). We investigated whether a similar enhancement can be observed in synaptically-induced LTD in 2–3-month-old mice (PP-LFS, Figure 1D-E). LTD was induced by 900-paired-pulses (50 ms interval) at 1 Hz (Oliet et al. , 1997) in the presence of L689,560 to block NMDA receptors. The degree of depression was significantly enhanced in slices from ArcKR mice (Figure 1D-E) consistent with previous findings using the G1-mGluR agonist DHPG to induce LTD (Wall et al. , 2018).