Conclusion
We have shown that the magnitude of LTP is diminished in hippocampal slices from ArcKR mice compared to WT mice and that induction of LTP facilitated by priming of GI-mGluR is impaired in ArcKR mice perhaps suggesting that below threshold activation of mGluR is sufficient to induce Arc protein expression triggering endocytosis of AMPA receptors. Previous studies have shown that when Arc expression is induced, the level of expression is enhanced, and the expression remains elevated for longer in ArcKR mice. Such enhancement could also occur when there is marked increases in neural activity during pathologies (such as during epileptic seizures) and could occur when there is Arc misexpression such as in Fragile X Syndrome (Niere et al. , 2012) and in neurodegenerative diseases. Our experiments using ArcKR expression, suggest that under these conditions it is possible that increased Arc expression could negatively modulate LTP and contribute to cognitive impairment.