EVIDENCE FOR CONSTITUTIVE PROTEIN SYNTHESIS IN HIPPOCAMPAL LTP STABILIZATION

The notion that blockade of constitutive protein synthesis underlies the effect of protein synthesis inhibitors (PSIs) on long-term potentiation (LTP) stabilization was examined using the rat hippocampal CA3-CA1 synapse. Using a biochemical assay we found protein synthesis rate largely recovered 1 h after wash-out of cycloheximide (CHX). Nonetheless, a 4-h CHX application followed by wash-out 1 h prior to LTP resulted in a significant decrement of LTP stabilization. Wash-out initiated just prior to LTP, thus extending protein synthesis inhibition well into the post-LTP period, resulted in no further effect on LTP. However, short pre- and continuous post-tetanization application of PSIs failed to influence LTP persistence for up to 7 h. Addition of hydrogen peroxide (H2O2) 5-25 min following LTP induction resulted in parallel depression of potentiated and non-potentiated inputs, leaving LTP seemingly unaltered. However, in the presence of cyxloheximide the H2O2 application resulted in a significant reduction of LTP. In conclusion: LTP stabilization was impaired by pre-LTP application of protein synthesis inhibition but not by post-LTP application unless the slices were exposed to oxidative stress. We submit that these results favor the notion that constitutive rather than triggered protein synthesis is important for LTP stabilization. (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.