Bryostatin-1 promotes long-term potentiation via activation of PKCα and PKCε in the hippocampus.

Activation of protein kinase C (PKC) by bryostatin-1 affects various functions of the central nervous system. We explored whether bryostatin-1 influenced synaptic plasticity via a process involving PKC. Our purpose was to examine whether bryostatin-1 affected the induction of hippocampal long-term potentiation (LTP) in Schaffer-collateral fibers (CA1 fibers) of the hippocampus, and/or influenced the intracellular Ca(2+) level of hippocampal neurons. We also determined the PKC isoforms involved in these processes. We found that bryostatin-1 strongly facilitated LTP induction, in a dose-dependent manner, upon single-theta burst stimulation (TBS). Further, intracellular Ca(2+) levels also increased with increasing concentration of bryostatin-1. The facilitative effects of bryostatin-1 in terms of LTP induction and enhancement of intracellular Ca(2+) levels were blocked by specific inhibitors of PKCα and PKCε, but not of PKCδ. Our results suggest that bryostatin-1 is involved in neuronal functioning and facilitates induction of LTP via activation of PKCα and/or PKCε.