The effects of protein kinase C activity on synaptic transmission in two areas of rat hippocampus

The effects of three protein kinase C (PKC) agonists (phorbol ester, ingenol and indolactam-V) and two PKC antagonists ( d- erythro-sphingosine and chelerythrine) on input–output (I–O) relations in the Schaffer collateral pathway to CA1 (SC-CA1) and mossy fiber pathway to CA3 (MF-CA3) were determined in rat hippocampus brain slices. In the SC-CA1 pathway, phorbol esters and indolactam-V had only small effects on field excitatory post-synaptic potentials (fEPSP) in slices from 60-day animals, although ingenol, an activator of novel PKC isozymes, caused a significant decrease of the field excitatory post-synaptic potentials amplitude in 60-day animals, but not in 30-day animals. In contrast, in the MF-CA3 pathway, PKC agonists induced a significant increase in the field excitatory post-synaptic potentials. PKC antagonists depressed the field excitatory post-synaptic potentials in the SC-CA1 pathway, but had no significant effect in the MF-CA3 pathway. In the MF-CA3 pathway, paired-pulse facilitation was abolished by PKC agonists and unaffected by antagonists. In SC-CA1, it was depressed by agonists to levels below control, whereas it was significantly increased by chelerythine. We conclude that PKC plays important but different roles in both regions. In the SC-CA1 pathway, PKC is almost maximally active under control circumstances, and PKC antagonists significantly reduce synaptic responses. In contrast, in the MF-CA3 pathway, there is no apparent activation under resting circumstances, but significant potentiation of synaptic transmission is induced when PKC is activated. There are developmental changes in the pattern of PKC isozymes, and both pre- and post-synaptic actions are important.