Synapse-specific protein kinase C activation enhances maintenance of long-term potentiation in rat hippocampus

Abstract

1. Protein kinase C (PKC) stimulators, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or cis-unsaturated fatty acid (UFA), have been shown to prolong synaptic enhancement induced by long-term potentiation (LTP). This observation suggests a role for PKC in the biochemical mechanisms underlying maintained enhancement. 2. To determine if PKC stimulators prolong LTP by acting selectively at synapses given high-frequency stimulation or by actions that are not synapse-specific (e.g. increased postsynaptic excitability) we examined the effect of TPA or UFA on input-selective enhancement. Population EPSPs, evoked in the same granule cell population by either the medial (MPP) or lateral (LPP) perforant path, can be selectively enhanced leaving the other perforant path input which receives only low-frequency stimulation as an internal control for PKC stimulator effects not specific to enhanced synapses. 3. Synapse-specific effects were in fact observed, as UFA or TPA selectively prolonged MPP enhancement following two trains of high-frequency MPP stimulation, without affecting responses evoked by the LPP. A similar synapse selectivity of PKC stimulator action was seen following high-frequency LPP stimulation. 4. These findings suggest that PKC stimulators prolong enhancement by acting specifically at high-frequency-stimulated synapses. PKC stimulators do not appear to affect either postsynaptic neurone excitability or synapses given only low-frequency stimulation. This provides further evidence that PKC acts synergistically with the consequences of repetitive synaptic activation to maintain enhancement.