Long-term depression of kainate receptor-mediated synaptic transmission

Kainate receptors (KARs) have been shown to be involved in hippocampal mossy fiber long-term potentiation (LTP); however, it is not known if KARs are involved in the induction or expression of long-term depression (LTD), the other major form of long-term synaptic plasticity. Here we describe LTD of KAR-mediated synaptic transmission (EPSCKA LTD) in perirhinal cortex layer II/III neurons that is distinct from LTD of AMPAR-mediated transmission, which also coexists at the same synapses. Induction of EPSCKA LTD requires a rise in postsynaptic Ca2+ but is independent of NMDARs or T-type voltage-gated Ca2+ channels; however, it requires synaptic activation of inwardly rectifying KARs and release of Ca2+ from stores. The synaptic KARs are regulated by tonically activated mGluR5, and expression of EPSCKA LTD occurs via a mechanism involving mGluR5, PKC, and PICK1 PDZ domain interactions. Thus, we describe the induction and expression mechanism of a form of synaptic plasticity, EPSCKA LTD.