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 18-day-old) rats, activation of group I metabotropic L-glutamate (mGlu) receptors by the specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) induces a form of long-term depression (LTD) of excitatory synaptic transmission. 2. We have used a variety of electrophysiological techniques applied to CA1 neurones in hippocampal slices and from pyramidal cells in dissociated hippocampal cultures to investigate the Ca2+ dependence and locus of expression 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 for the duration of the recording (up to 2 h after commencing washout of DHPG) in 27 of 29 neurones investigated. 4. DHPG-induced LTD was associated with an increase in both the paired-pulse facilitation ratio and the coefficient of variation of EPSCs. 5. Using dendritic recording, there was a decrease in EPSC success rate (number of trials that elicited a detectable response) but no change in potency (mean EPSC amplitude excluding failures) associated with DHPG-induced LTD. 6. In experiments using dissociated hippocampal cultures, application of DHPG elicited a persistent decrease in the frequency of tetrodotoxin-resistant miniature EPSCs but no change in the amplitude of such events. 7. DHPG-induced LTD was not blocked by intracellular application of the calcium chelator BAPTA. It was also unaffected when intracellular calcium stores were depleted by perfusion with thapsigargin. Furthermore, when synaptic transmission was blocked by perfusing with Ca2+-free medium, DHPG application reliably induced LTD. 8. These data suggest that DHPG-induced LTD is Ca2+ independent and is expressed presynaptically.