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.