mGluR-mediated and endocannabinoid-dependent long-term depression in the hilar region of the rat dentate gyrus

We report that bath application of the group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) causes acute inhibition of evoked IPSCs recorded from hilar mossy cells, and that significant long-term depression (LTD) of synaptic transmission remains following washout of DHPG. Subsequent experiments using minimal stimulation techniques revealed that expression of both acute and long-term effects of DHPG are restricted to a subset of GABAergic afferents that are also sensitive to depolarization-induced suppression of inhibition (DSI). Experiments with a selective CB1 antagonist and with transgenic animals lacking CB1 receptors indicate that all effects of DHPG, like DSI, depend on activation of CB1 receptors. Further work with selective mGluR antagonists suggests a direct involvement of mGluR1 receptors. Interestingly, we also report that induction of LTD under our experimental conditions does not require prior direct somatic depolarization via the patch pipette and does not appear to depend critically on the level of activity in incoming GABAergic afferents. Collectively, these results represent the first characterization of mGluR-mediated and endocannabinoid-dependent LTD in the hilar region of the dentate gyrus. The dentate gyrus is thus one of relatively few areas where this mechanism has clearly been demonstrated to induce long-term modulation of inhibitory synaptic transmission.