Low‐frequency stimulation of the direct cortical input to area CA1 induces homosynaptic LTD and heterosynaptic LTP in the rat hippocampal–entorhinal cortex slice preparation

The entorhinal cortex (EC) innervates area CA1 and the subiculum directly via the portion of the perforant path, which originates from EC layer III cells referred to as direct cortical input (dCI), and indirectly via the trisynaptic loop through the dentate gyrus and area CA3. The dCI is of great importance as it mediates positional information for activation of place cells that is not prevented after interrupting information flow from area CA3 to CA1. In this study, we investigated the effects of low-frequency stimulation of the dCI on homo- and heterosynaptic plasticity in area CA1 and tested for the contribution of NMDA, GABA(A), GABA(B), kainate and group I mGlu receptors. We demonstrate that 1 Hz stimulation of the dCI induces homosynaptic long-term depression (LTD) and that 1 Hz stimulation of the dCI induces a long-lasting augmentation of stratum radiatum-induced population spikes in area CA1 (heterosynaptic long-term potentiation). Additionally we show that homosynaptic effects depend on activation of GABA(B) and kainate receptors, whereas the heterosynaptic effects are GABA(A) and mGlu receptor dependent.