Investigations of the protein synthesis dependency of mGluR-induced long-term depression in the dentate gyrus of freely moving rats.

Hippocampal long-term depression (LTD) comprises an activity-dependent weakening of synaptic strength. In this study we compared persistent LTD induced by the group I mGluR agonist, DHPG, or the group III mGluR agonist, AP4, in the dentate gyrus of freely moving rats. The role of protein translation, using the translation inhibitors, anisomycin and emetine, was also investigated. Potentials were evoked from medial perforant path-dentate gyrus granule cell synapses of male Wistar rats by means of chronically implanted electrodes. Immediately after intracerebral (ventricular) application of DHPG or AP4 robust LTD (>24 h) occurred. Paired-pulse analysis during LTD, and application of mGluR antagonists after stabilisation of depression, supported that LTD genuinely occurred and that the depression was not a consequence of persistence of the agonists at the synapse. Application of a protein synthesis inhibitor 2 h prior to DHPG injection inhibited the expression of LTD (from ca. 6 h post-injection) but did not affect LTD induced by AP4. These data highlight differences in chemical LTD elicited by group I and group III mGluRs. Whereas AP4-induced LTD may arise as a result of modulation of presynaptic glutamate release mechanisms, the protein synthesis dependency of DHPG-induced LTD suggests an additional postsynaptic expression mechanism for this phenomenon.