Hostname: page-component-54dcc4c588-m259h Total loading time: 0 Render date: 2025-09-12T17:34:31.363Z Has data issue: false hasContentIssue false
  • English
  • Français

The Biochemical Basis of Long-Term Memory

Published online by Cambridge University Press:  17 March 2009

Richard B. Roberts  and
Louis B. Flexner
Richard B. Roberts
Affiliation:
Department of Terrestrial Magnetism, Carnegie Institution of Washington, Washington, D.C.
Louis B. Flexner
Affiliation:
Department of Anatomy, University of Pennsylvania, Philadelphia, Pennsylvania 19104
Get access Rights & Permissions [Opens in a new window]

Extract

Learning and memory are important elements of our daily lives, familiar to all through introspection. Yet the mechanisms underlying these processes are still for the most part unknown. Here are problems which combine a maximum of intrinsic and practical interest with a minimum of actual knowledge and understanding. Years of our lives are dedicated to the formation of certain long-term memories and behaviour patterns, yet we have only rudimentary notions of how such ‘schooling’ is best accomplished. There is no certainty in any aspect of the process. We are not sure whether relatively few cells or millions participate in a memory trace; whether these cells change as a whole, or whether the changes are limited to synaptic regions. In fact, we cannot be certain whether the changes are confined to the neurones or whether the glia also participate.

Information

Type
Research Article
Information
Quarterly Reviews of Biophysics , Volume 2 , Issue 2 , May 1969 , pp. 135 - 173
Copyright
Copyright © Cambridge University Press 1969

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

REFERENCES

Adair, L. B., Wilson, J. E. & Glassman, E. (1968 b). Brain function and macromolecules. IV. Uridine incorporation into polysomes of mouse brain during different behavioural experiences. Proc. natn. Acad. Sci. U.S.A. 61, 917–22.CrossRefGoogle Scholar
Adair, L. B., Wilson, J. E., Zemp, J. W. & Glassman, E. (1968 a). Brain function and macromolecules. III. Uridine incorporation into polysomes of mouse brain during short-term avoidance conditioning. Proc. natn. Acad. Sci. U.S.A. 61, 606–13.CrossRefGoogle Scholar
Agranoff, B. W. (1967). Agents that block memory. In The Neurosciences: A Study Program, pp. 756–64. Ed. Quarton, G. C. and Melnechuk, T.. New York: Rockefeller University Press.Google Scholar
Agranoff, B. W., Davis, R. E. & Brink, J. J. (1965). Memory fixation in the goldfish. Proc. natn. Acad. Sci. U.S.A. 54, 788–93.CrossRefGoogle ScholarPubMed
Agranoff, B. W., Davis, R. E. & Brink, J. J. (1966). Chemical studies of memory fixation in goldfish. Brain Res. I, 303–9.CrossRefGoogle Scholar
Agranoff, B. W., Davis, R. E., Casola, L. & Lim, R. (1967). Actinomycin ‘D’ blocks formation of memory of shock avoidance in goldfish. Science, N.Y. 158, 1600–1.CrossRefGoogle ScholarPubMed
Agranoff, B. W. & Klinger, P. D. (1964). Puromycin effect on memory fixation in the goldfish. Science, N.Y. 146, 952–3.CrossRefGoogle ScholarPubMed
Barondes, S. H. (1965). Relationship of biological regulatory mechanisms to learning and memory. Nature, N.Y. 205, 18–21.CrossRefGoogle ScholarPubMed
Barondes, S. H. & Cohen, H. D. (1966). Puromycin effect on successive phases of memory storage. Science, N.Y. 151, 594–5.CrossRefGoogle ScholarPubMed
Barondes, S. H. & Cohen, H. D. (1967). Delayed and sustained effect of acetoxycycloheximide on memory in mice. Proc. natn. Acad. Sci. U.S.A. 58, 157–64.CrossRefGoogle ScholarPubMed
Baroneds, S. H. & Cohen, H. D. (1968 a). Memory impairment after subcutaneous injection of acetoxycycloheximide. Science, N. Y. 160, 556–7.CrossRefGoogle Scholar
Barondes, S. H. & Cohen, H. D. (1968 b). Arousal and the conversion of short- term memory to long-term memory. Proc. natn. Acad. Sci. U.S.A. 61,923–9.CrossRefGoogle ScholarPubMed
Barondes, S. H. & Jarvik, M. E. (1964). The influence of actinomycin-D on brain RNA synthesis and on memory. J. Neurochem. II, 187–95.CrossRefGoogle Scholar
Bohus, B. & De, Wied D. (1966). Inhibitory and facilitory effect of two related peptides on extinction of avoidance behavior. Science, N. Y. 153, 318–20.CrossRefGoogle Scholar
Bovet, D., Bovet-Nitti, F. & Olivero, A. (1969). Genetic aspects of learning and memory in mice. Science, N.Y. 163, 139–49.CrossRefGoogle ScholarPubMed
Brink, J. J., Davis, R. E. & Agranoff, B. W. (1966). Effects of puromycin, acetoxycycloheximide, and actinomycin D on protein synthesis in goldfish brain. J. Neurochem. 13, 889–96.CrossRefGoogle ScholarPubMed
Britten, R. J. & Kohne, D. E. (1968). Repeated sequences in DNA. Science, N.Y. 161, 529–40.CrossRefGoogle ScholarPubMed
Buresova, O. & Bures, J. (1965). Interhemispheric synthesis of memory traces. J. comp. physiol. Psychol. 59, 211–14.CrossRefGoogle ScholarPubMed
Casola, L., Lim, R., Davis, R. E. & Agranoff, B. W. (1968). Behavioral and biochemical effects of intracranial injection of cytosine arabinoside in goldfish. Proc. natn. Acad. Sci. U.S.A. 60, 1389–95.CrossRefGoogle ScholarPubMed
Chamberlain, T. J., Rothschild, G. H. & Gerard, R. W. (1963). Drugs affecting RNA and learning. Proc. natn. Acad. Sci. U.S.A 49, 918–24.CrossRefGoogle ScholarPubMed
Cohen, H. D. & Barondes, S. H. (1966). Further studies of learning and memory after intracerebral actinomycin-D. J. Neurochem. 13, 207–11.CrossRefGoogle ScholarPubMed
Cohen, H. D. & Barondes, S. H. (1967). Puromycin effect on memory may be due to occult seizures. Science, N.Y. 157, 333–4.CrossRefGoogle ScholarPubMed
Cohen, H. D. & Barondes, S. H. (1968). Effect of acetoxycycloheximide on learning and memory of a light—dark discrimination. Nature, Lond. 218, 271–3.CrossRefGoogle ScholarPubMed
Cohen, H. D., Ervin, F. & Barondes, S. H. (1966). Puromycin and cycloheximide: different effects on hippocampal electrical activity. Science, N.Y. 154, 1557–8.CrossRefGoogle ScholarPubMed
Davis, R. E. & Agranoff, B. W. (1966). Stages of memory formation in goldfish: evidence for an environmental trigger. Proc. natn. Acad. Sci. U.S.A 55, 555–9.CrossRefGoogle ScholarPubMed
Dingman, W. & Sporn, M. B. (1961). The incorporation of 8-azaguanine into rat brain RNA and its effect on maze-learning. J. Psychiatric Res. I, 1–11.CrossRefGoogle Scholar
Flexner, L. B. & Flexner, J. B. (1966). Effect of acetoxycycloheximide and of an acetoxycycloheximide-puromycin mixture on cerebral protein synthesis and memory in mice. Proc. natn. Acad. Sci. U.S.A 55, 369–74.CrossRefGoogle ScholarPubMed
Flexner, J. B. & Flexner, L. B. (1967). Restoration of expression of memory lost after treatment with puromycin. Proc. natn. Acad. Sci. U.S.A 57, 1651–4.CrossRefGoogle ScholarPubMed
Flexner, L. B. & Flexner, J. B. (1968 a). Intracerebral saline: effect on memory of trained mice treated with puromycin. Science, N.Y. 159, 330–1.CrossRefGoogle ScholarPubMed
Flexner, L. B. & Flexner, J. B. (1968 b). Studies on memory: the long survival of peptidyl-puromycin in the mouse brain. Proc. natn. Acad. Sci. U.S.A 60, 923–7.CrossRefGoogle Scholar
Flexner, L. B., Flexner, J. B. & Roberts, R. B. (1958). Biochemical and physiological differentiation during morphogenesis. 22. Observations on amino acid and protein synthesis in the cerebral cortex and liver of the newborn mouse. J. cell. comp. Physiol. 51, 385–403.CrossRefGoogle Scholar
Flexner, L. B., Flexner, J. B. & Roberts, R. B. (1966). Stages of memory in mice treated with acetoxycycloheximide before or immediately after learning. Proc. natn. Acad. Sci. U.S.A 56, 730–5.CrossRefGoogle ScholarPubMed
Flexner, L. B., Flexner, J. B. & Roberts, R. B. (1967). Memory in mice analyzed with antibiotics. Science, N.Y. 155, 1377–83.CrossRefGoogle ScholarPubMed
Flexner, L. B., Flexner, J. B., Roberts, R. B. & De La Haba, G. (1964). Loss of recent memory in mice as related to regional inhibition of cerebral protein synthesis. Proc. natn. Acad. Sci. U.S.A 52, 1165–9.CrossRefGoogle ScholarPubMed
Flexner, J. B., Flexner, J. B. & Stellar, E. (1963). Memory in mice as affected by intracerebral puromycin. Science, N.Y. 141, 57–9.CrossRefGoogle ScholarPubMed
Flexner, L. B., Flexner, J. B. & Stellar, E. (1965). Memory and cerebral protein synthesis in mice as affected by graded amounts of puromycin. Expl Neurol. 13, 264–72.CrossRefGoogle ScholarPubMed
Flexner, J. B., Flexner, L. B., Stellar, E., Haba, G. De La & Roberts, R. B. (1962). Inhibition of protein synthesis in brain and learning and memory following puromycin. J. Neurochem. 9, 595–605.CrossRefGoogle ScholarPubMed
Gambetti, P., Gonatas, N. K. & Flexner, L. B. (1968 a). The fine structure of puromycin-induced changes in mouse entorhinal cortex. J. Cell Biol. 36, 379–90.CrossRefGoogle ScholarPubMed
Gambetti, P., Gonatas, N. K. & Flexner, L. B. (1968 b). Puromycin: action on neuronal mitochondria. Science, N.Y., 161, 900–2.CrossRefGoogle ScholarPubMed
Griffith, J. S. (1968). Mathematics of cellular control processes. I: Negative feedback to one gene. II. Positive feedback to one gene. J. theoret. Biol. 20, 202–16.CrossRefGoogle Scholar
Hyden, H. & Egyhazi, E. (1962). Nuclear RNA changes of nerve cells during a learning experiment in rats. Proc. natn. Acad. Sci. U.S.A 48, 1366–72.CrossRefGoogle ScholarPubMed
Hyden, H. & Egyhazi, E. (1963). Glial RNA changes during a learning experiment in rats. Proc. natn. Acad. Sci. U.S.A 49, 618–24.CrossRefGoogle ScholarPubMed
Hyden, H. & Egyhazi, E. (1964). Changes in RNA content and base composition in cortical neurons of rats in a learning experiment involving transfer of handedness. Proc. natn. Acad. Sci. U.S.A 52, 1030–5.CrossRefGoogle Scholar
Hyden, H. & Lange, P. W. (1968). Protein synthesis in the pyramidal cells of rats during a behavioural test. Science, N.Y. 159, 1370–3.CrossRefGoogle Scholar
John, E. R. (1967). Mechanisms of Memory, pp. 246–53. New York: Academic Press.Google Scholar
Misanin, J. R., Miller, R. R. & Lewis, D. J. (1968). Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace. Science, N. Y. 160, 554–5.CrossRefGoogle ScholarPubMed
McGaugh, J. L. (1966). Time-dependent processes in memory storage. Science, N.Y. 153, 1351–8.CrossRefGoogle ScholarPubMed
Orrego, F. & Lipmann, F. (1967). Protein synthesis in brain slices. (Effects of electrical stimulation and acidic amino acids.) J. biol. Chem. 242, 665–70.CrossRefGoogle ScholarPubMed
Potts, A. & Bitterman, M. E. (1967). Puromycin and retention in the goldfish. Science, N.Y. 158, 1594–6.CrossRefGoogle ScholarPubMed
Roberts, R. B. & Flexner, L. B. (1966). A model for the development of retina—cortex connections. Am. Scient. 54, 174–83.Google Scholar
Roberts, R. B., Flexner, J. B. & Flexner, L. B. (1959) Biochemical and physiological differentiation during morphogenesis. 23. Further observations relating to synthesis of amino acids and protein by the cerebral cortex and liver of the mouse. J. Neurochem. 4, 78–90.CrossRefGoogle Scholar
Shashoua, V. E. (1968). RNA changes in goldfish brain during learning. Nature, Lond. 217, 238–40.CrossRefGoogle ScholarPubMed
De Wied, D. & Bohus, B. (1966). Long- and short-term effects on retention of a conditioned avoidance response in rats by treatment with long acting pitressin and α MSH. Nature, Lond. 212, 1484–6.CrossRefGoogle ScholarPubMed
Zemp, J. W., Wilson, J. E. & Glassman, E. (1967). Brain function and macromolecules. II. Site of increased labeling of RNA in brains of mice during a short-term training experience. Proc. natn. Acad. Sci. U.S.A 58, 1120–5.CrossRefGoogle ScholarPubMed
Zemp, J. W., Wilson, J. E., Schlesinger, K., Boggan, W. O. & Glassman, E. (1966). Brain function and macromolecules. I. Incorporation of uridine into RNA of mouse brain during short-term training experience. Proc. natn. Acad. Sci. U.S.A 55, 1423–30.CrossRefGoogle ScholarPubMed