Differential effects of the group II mGluR agonist, DCG-IV, on depolarization-induced suppression of inhibition in hippocampal CA1 and CA3 neurons.

We investigated the role of metabotropic glutamate receptors in the mediation of depolarization-induced suppression of inhibition (DSI), using whole-cell electrophysiological techniques in rat hippocampal slice preparation. In a previous work, we showed that a retrograde signal travels from CA1 pyramidal cells to GABA interneurons and prevents them from releasing GABA for tens of seconds at 30 degrees C. The resulting suppression of inhibition is DSI. The retrograde signal appeared to be glutamate, or a glutamate analog, which acted on group I metabotropic receptors on the interneurons. It is not known if DSI occurs in hippocampal subregions besides CA1. If DSI does occur in other regions, it will be important to know if the role of metabotropic glutamate receptors (mGluRs) in mediating DSI is the same everywhere. The distribution of mGluR subtypes varies among hippocampal subregions. In the CA3 region, unlike CA1, group II mGluRs are prevalent. It was possible, therefore, that in CA3, the group II mGluRs would mediate DSI. We have begun to investigate these issues. We now report that: 1) DSI does occur in CA3. 2) Carbachol induces IPSC activity that can be recorded in CA1 and CA3a. This carbachol-induced activity can be reduced by the selective group II mGluR agonist, DCG-IV, and by DSI. 3) Evoked IPSCs in CA3a, but not in CA1, can be reduced by DCG-IV; hence the interneurons activated by carbachol may reside in CA3a. 4) Despite the group II mGluR agonist sensitivity of CA3a interneurons, DSI in this region is not affected by a group II mGluR antagonist, CPPG, and therefore does not appear to be mediated by group II mGluRs.