Role of protein kinase C in the induction of homosynaptic long-term depression by brief low frequency stimulation in the dentate gyrus of the rat hippocampus in vitro

1. Enhancement of the induction of long-term depression (LTD) of excitatory postsynaptic currents (EPSCs) by a priming stimulus was investigated in th e medial perforant pathway of the dentate gyrus of the hippocampus in vitro . 2. In control, LTD could be induced by a conditioning low frequency stimula tion (LFS) consisting of sixty, although not thirty or fewer, stimuli at 1 Hz applied at a holding potential of -40 mV. 3. A conditioning LFS of just five stimuli at 1 Hz was-found to induce LTD if preceded 1-5 min, but not 15 min, by a priming LFS of five stimuli at 1 Hz, -40 mV, which did not by itself induce LTD. 4. A low concentration of the protein kinase C (PKC) activator (-)-indolact am V, which did not itself induce LTD, reduced the threshold for the number of stimuli inducing LTD following the priming stimulus, while a high conce ntration of (-)-indolactam V directly induced a depression of the test exci tatory postsynaptic current (EPSC), which occluded LFS-induced LTD. This su ggests that the priming of LTD and also the direct induction of LTD involve s the activation of PKC. 5. The pseudosubstrate peptide inhibitor PKC19-36 inhibited the induction o f LTD by the priming protocol and by the control induction conditioning pro tocol. 6. These experiments demonstrate that a covert synaptic change involving ge neration of PKC is very effective in producing conditions whereby LTD is in duced by very brief synaptic stimulation.