Research ReportEmetine treatment masks initial LTP without affecting long-term stability

Applying emetine, a protein synthesis inhibitor, at 20-40 μM for 90-120 min prior to LTP induction in hippocampal slices from young rats (2-3 weeks) and washing it out afterwards revealed a slowly developing potentiation that reached maximum after 20-30 min, distinct from the LTP observed under normal conditions. Nevertheless, the later phase of this potentiation was similar to standard LTP as judged by experiments lasting up to 8 h after induction. Emetine preapplication for 3 h without subsequent washout resulted in a substantial decay of evoked responses. By comparison between test and control pathways, LTP could still be assessed in these experiments for up to 4-6 h after induction and was found not to differ from normal, except for the slow onset. The NMDA-R blocker AP5 fully blocked LTP; however, with emetine pretreatment there was an initial depression of responses with a gradual recovery during 20-30 min. This depression involved not only the field EPSP but also the presynaptic fiber volley. However, when using the protein synthesis inhibitors cycloheximide and anisomycin there was essentially no such depression. In conclusion, the present results support the idea that preexisting proteins are sufficient for inducing stable LTP. Moreover, emetine but not anisomycin or cycloheximide impairs presynaptic action potentials, leading to an apparent slow onset of LTP. The emetine-dependent effect could be due to a characteristic blocking spectrum of the drug, preferred targeting of presynaptic compartments or effects unrelated to protein synthesis.

► We examine LTP in hippocampal slices after long perfusion with the protein synthesis inhibitor emetine. ► Our recordings reveal a slowly developing potentiation peaking after 20-30 min, distinct from control LTP. ► The slow onset is due to a transient depression of presynaptic firing, masking the initial part of LTP. ► Late LTP was unaffected by emetine, contrasting with the prevailing dogma that newly synthesized proteins are needed. ► Emetine may act specifically on availability of action potential related proteins such as ion pumps and channels.