Requirement of translation but not transcription for the maintenance of long-term depression in the CA1 region of freely moving rats

Hippocampal long-term depression (LTD) comprises a persistent reduction in synaptic strength that can be induced in the CA1 region by repeated low-fre quency stimulation (LFS). Previous studies have demonstrated that hippocamp al long-term potentiation requires de novo protein synthesis. Whether hippo campal LTD is also protein synthesis-dependent is not known. In this study, we investigated if the previous administration of translation inhibitors ( anisomycin or emetine) or a transcription inhibitor (actinomycin-D) influen ced the profile of LTD in freely moving adult Wistar rats. Seven- to 8-week -old animals underwent chronic implantation of a recording electrode in the CA1 stratum radiatum and a stimulation electrode in the Schaffer collatera l/commissural fiber pathway. A cannula was implanted in the ipsilateral cer ebral ventricle to enable drug administration. Experiments were commenced 1 0 d after the implantation procedure. Immediately after application of LFS (1 Hz, 900 pulses) robust LTD was seen that persisted for >8 hr in control animals. Application of anisomycin (240 mug/5 ml) emetine (240 mg/5 ml) bef ore LFS prevented the expression of LTD or similar to4.5 hr after LFS. Prev ious administration of actinomycin D (72 mug/12 ml) had no effect on the ex pression of LTD. None of the compounds elicited significant effects on basa l synaptic transmission when administered in the absence of LFS. These data suggest that LTD in the CA1 region in vivo is protein synthesis-dependent. Furthermore, persistent LTD can be established through the translation of existing mRNA, whereas de novo mRNA transcription does not appear to be nec essary.