Metabotropic glutamate receptors modulate feedback inhibition in a developmentally regulated manner in rat dentate...

We investigated group II metabotropic glutamate receptor (mGluR) modulation of glutamatergic input onto hilar-border interneurones and its regulation of feedback inhibition in the dentate gyrus. Selective activation of group II mGluRs with (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV) depressed mossy fibre (MF)-evoked excitatory drive to these interneurones with significantly greater depression in juvenile than adult rats. During 20 Hz MF stimulus trains, EPSCs became depressed. Depression during the early, but not later part of the train was significantly greater in juvenile than adult rats and was blocked by the mGluR antagonist (2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495). In dentate granule cells from juvenile rats polysynaptic feedback IPSCs, but not monosynaptic IPSCs, were strongly suppressed by DCG-IV. DCG-IV also suppressed feedback inhibition of perforant path-evoked population spikes. In contrast, in adult animals DCG-IV did not significantly depress feedback inhibition. During 20 Hz stimulus trains in juvenile animals the summation of polysynaptic, but not monosynaptic IPSCs was suppressed by synaptically activated group II mGluRs. Blockade of these mGluRs with LY341495 significantly increased the area and duration of the summated IPSC, causing greater feedback inhibition of granule cell firing. In contrast, in adult animals LY341495 did not alter feedback inhibition following the stimulus train. These findings indicate that group II mGluRs modulate excitatory drive to interneurones in a developmentally regulated manner and thereby modulate feedback inhibition in the dentate gyrus.