Fig. 4

KA receptors contributes to the regulation of synaptic transmission and presynaptic LTP in cingulate cortex. At excitatory synapses in the ACC (left side, lower panel), glutamate mediates excitatory transmission, and postsynaptic KA receptors (GluK1 and 2) mediate some of postsynaptic response in addition to AMPA receptors. GluK1 containing KA receptors also locate at presynaptic terminals, and its activation contributes to presynaptic form of LTP. The presynaptic Ca²⁺ influx via GluK1 KARs leads to activation of the AC1-PKA pathway, which then results in modulation of HCN channels resulting in a long-lasting increase in glutamate release. At inhibitory synapses in the ACC (left side, top panel), presynaptic GluK1 KA receptors also regulate the release of GABA in a biphasic manner. The exact signaling mechanism remains to be investigated though