INFLUENCE OF ACTINOMYCIN-D, A RNA-SYNTHESIS INHIBITOR, ON LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL-NEURONS IN-VIVO AND IN-VITRO

1. Hippocampal long-term potentiation (LTP) may serve as an elementary process underlying certain forms of learning and memory in vertebrate s. As is the case with behavioural memory, hippocampal LTP in the rat CA1 region and in the dentate gyrus occurs in stages, which can be sep arated by an inhibitor of RNA synthesis. 2. Experiments have been perf ormed in two brain regions, in the hippocampal CA1 region in vitro and in the dentate gyrus in vivo. 3. Maintenance of hippocampal LTP in th e CA1 region in vitro was influenced by the RNA synthesis inhibitor ac tinomycin D from 4 h onwards. 4. The effect of actinomycin D on the ti me course of the population spike potentiation was more pronounced tha n the effect on the time course of the EPSP component, suggesting diff erent mechanisms for the two forms of potentiation. 5. Intrahippocampa l and intracerebroventricular injection of actinomycin D into rats pre vented a late stage of LTP in the dentate gyrus in vivo measured as th e population spike amplitude. 6. Since actinomycin D was only effectiv e in influencing the maintenance of LTP when applied before tetanizati on, the requirement for transcription during LTP may have a critical t ime window. 7. Actinomycin D influenced the maintenance of LTP specifi cally, since the drug did not alter any potentials in control experime nts after its removal or when it was administered shortly after tetani zation. A second, structurally different RNA synthesis inhibitor, 5,6- dichloro-1-beta-D-ribofuranosyl benzimidazole, mimicked the effect of actinomycin D in vitro.