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Logo of jphysiolThe Journal of Physiology SiteMembershipSubmissionJ Physiol
J Physiol. Feb 1, 1996; 490(Pt 3): 703–711.
PMCID: PMC1158708

Influence of actinomycin D, a RNA synthesis inhibitor, on long-term potentiation in rat hippocampal neurons in vivo and in vitro.

Abstract

1. Hippocampal long-term potentiation (LTP) may serve as an elementary process underlying certain forms of learning and memory in vertebrates. 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 separated by an inhibitor of RNA synthesis. 2. Experiments have been performed in two brain regions, in the hippocampal CA1 region in vitro and in the dentate gyrus in vivo. 3. Maintenance of hippocampal LTP in the CA1 region in vitro was influenced by the RNA synthesis inhibitor actinomycin D from 4 h onwards. 4. The effect of actinomycin D on the time course of the population spike potentiation was more pronounced than the effect on the time course of the EPSP component, suggesting different mechanisms for the two forms of potentiation. 5. Intrahippocampal and intracerebroventricular injection of actinomycin D into rats prevented a late stage of LTP in the dentate gyrus in vivo measured as the population spike amplitude. 6. Since actinomycin D was only effective in influencing the maintenance of LTP when applied before tetanization, the requirement for transcription during LTP may have a critical time window. 7. Actinomycin D influenced the maintenance of LTP specifically, since the drug did not alter any potentials in control experiments after its removal or when it was administered shortly after tetanization. A second, structurally different RNA synthesis inhibitor, 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole, mimicked the effect of actinomycin D in vitro.

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Selected References

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  • Abraham WC, Dragunow M, Tate WP. The role of immediate early genes in the stabilization of long-term potentiation. Mol Neurobiol. 1991;5(2-4):297–314. [PubMed]
  • Alkon DL, Amaral DG, Bear MF, Black J, Carew TJ, Cohen NJ, Disterhoft JF, Eichenbaum H, Golski S, Gorman LK, et al. Learning and memory. FESN Study Group. Brain Res Brain Res Rev. 1991 May-Aug;16(2):193–220. [PubMed]
  • Bliss TV, Collingridge GL. A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993 Jan 7;361(6407):31–39. [PubMed]
  • Chinestra P, Leinekugel X, Ben Ari Y, Pollard H. Use of hippocampal slices to study mRNA changes in relation to synaptic plasticity. Neuroreport. 1994 Jul 21;5(12):1461–1465. [PubMed]
  • Cole AJ, Saffen DW, Baraban JM, Worley PF. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature. 1989 Aug 10;340(6233):474–476. [PubMed]
  • Daniels D. Effects of actinomycin D on memory and brain RNA synthesis in an appetitive learning task. Nature. 1971 Jun 11;231(5302):395–397. [PubMed]
  • Demmer J, Dragunow M, Lawlor PA, Mason SE, Leah JD, Abraham WC, Tate WP. Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats. Brain Res Mol Brain Res. 1993 Mar;17(3-4):279–286. [PubMed]
  • Dragunow M, Abraham WC, Goulding M, Mason SE, Robertson HA, Faull RL. Long-term potentiation and the induction of c-fos mRNA and proteins in the dentate gyrus of unanesthetized rats. Neurosci Lett. 1989 Jul 3;101(3):274–280. [PubMed]
  • Fazeli MS, Corbet J, Dunn MJ, Dolphin AC, Bliss TV. Changes in protein synthesis accompanying long-term potentiation in the dentate gyrus in vivo. J Neurosci. 1993 Apr;13(4):1346–1353. [PubMed]
  • Frey U, Huang YY, Kandel ER. Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons. Science. 1993 Jun 11;260(5114):1661–1664. [PubMed]
  • Frey U, Krug M, Reymann KG, Matthies H. Anisomycin, an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res. 1988 Jun 14;452(1-2):57–65. [PubMed]
  • Gilbert ME, Mack CM. The NMDA antagonist, MK-801, suppresses long-term potentiation, kindling, and kindling-induced potentiation in the perforant path of the unanesthetized rat. Brain Res. 1990 Jun 11;519(1-2):89–96. [PubMed]
  • Grecksch G, Matthies H. Two sensitive periods for the amnesic effect of anisomycin. Pharmacol Biochem Behav. 1980 May;12(5):663–665. [PubMed]
  • Huang YY, Kandel ER. Recruitment of long-lasting and protein kinase A-dependent long-term potentiation in the CA1 region of hippocampus requires repeated tetanization. Learn Mem. 1994 May-Jun;1(1):74–82. [PubMed]
  • Jeffery KJ, Abraham WC, Dragunow M, Mason SE. Induction of Fos-like immunoreactivity and the maintenance of long-term potentiation in the dentate gyrus of unanesthetized rats. Brain Res Mol Brain Res. 1990 Oct;8(4):267–274. [PubMed]
  • Krug M, Lössner B, Ott T. Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats. Brain Res Bull. 1984 Jul;13(1):39–42. [PubMed]
  • Link W, Konietzko U, Kauselmann G, Krug M, Schwanke B, Frey U, Kuhl D. Somatodendritic expression of an immediate early gene is regulated by synaptic activity. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5734–5738. [PMC free article] [PubMed]
  • Matthies H, Frey U, Reymann K, Krug M, Jork R, Schroeder H. Different mechanisms and multiple stages of LTP. Adv Exp Med Biol. 1990;268:359–368. [PubMed]
  • Montarolo PG, Goelet P, Castellucci VF, Morgan J, Kandel ER, Schacher S. A critical period for macromolecular synthesis in long-term heterosynaptic facilitation in Aplysia. Science. 1986 Dec 5;234(4781):1249–1254. [PubMed]
  • Nguyen PV, Abel T, Kandel ER. Requirement of a critical period of transcription for induction of a late phase of LTP. Science. 1994 Aug 19;265(5175):1104–1107. [PubMed]
  • Otani S, Marshall CJ, Tate WP, Goddard GV, Abraham WC. Maintenance of long-term potentiation in rat dentate gyrus requires protein synthesis but not messenger RNA synthesis immediately post-tetanization. Neuroscience. 1989;28(3):519–526. [PubMed]
  • Qian Z, Gilbert ME, Colicos MA, Kandel ER, Kuhl D. Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature. 1993 Feb 4;361(6411):453–457. [PubMed]
  • Steward O, Wallace CS. mRNA distribution within dendrites: relationship to afferent innervation. J Neurobiol. 1995 Mar;26(3):447–449. [PubMed]
  • Wetzel W, Ott T, Matthies H. Is actinomycin D suitable for the investigation of memory processes? Pharmacol Biochem Behav. 1976 May;4(5):515–519. [PubMed]
  • Worley PF, Bhat RV, Baraban JM, Erickson CA, McNaughton BL, Barnes CA. Thresholds for synaptic activation of transcription factors in hippocampus: correlation with long-term enhancement. J Neurosci. 1993 Nov;13(11):4776–4786. [PubMed]

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