A characterisation of long-term depression induced by metabotropic glutamate receptor activation in the rat hippocampus in vitro

1. In the CA1 region of hippocampal slices prepared from juvenile (12- to 1 8-day-old) rats, activation of group I metabotropic L-glutamate (mGlu) rece ptors by the specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) induce s a form of long-term depression (LTD) of excitatory synaptic transmission. 2. We have used a variety of electrophysiological techniques applied to CAI neurones in hippocampal slices and from pyramidal cells in dissociated hip pocampal cultures to investigate the Ca2+ dependence and locus of expressio n of DHPG-induced LTD, 3. In patch-clamp experiments from hippocampal slices, bath application of DHPG induced a depression of synaptically evoked responses that persisted f or the duration of the recording (up to 2 h after commencing washout of DHP G) in 27 of 29 neurones investigated. 4. DHPG-induced LTD was associated with an increase in both the paired-puls e facilitation ratio and the coefficient of variation of EPSCs. 5. Using dendritic recording, there was a decrease in EPSC success rate (nu mber of trials that elicited a detectable response) but, no change in poten cy (mean EPSC amplitude excluding failures) associated with DHPG-induced LT D. 6. In experiments using dissociated hippocampal cultures, application of DH PG elicited a persistent decrease in the frequency of tetrodotoxin-resistan t miniature EPSCs but no change in the amplitude of such events. 7. DHPG-induced LTD was not blocked by intracellular application of the cal cium chelator BAPTA. It was also unaffected when intracellular calcium stor es were depleted by perfusion with thapsigargin. Furthermore, when synaptic transmission was blocked by perfusing with Ca2+-free medium, DHPG applicat ion reliably induced LTD. 8. These data suggest that DHPG-induced LTD is Ca2+ independent and is expr essed presynaptically.