The Role of Brain Extracellular Proteins in Learning and Memory

  • Victor E. Shashoua

Abstract

In mammalian brain, the cellular and biochemical mechanisms of learning and memory have the capacity to store information for long periods, in man, this may be upwards of 50 years. How is this achieved? If we search the components of the CNS looking for molecules that can fulfill this criterion of long-term stability, we find that everything except the DNA is in a dynamic state. The average half-life of proteins ranges between 6 and 14 days (Lajtha and Toth, 1966); the RNA turnover can vary from 1.5 to 24 hr (Appel, 1967); lipids and carbohydrates are in a rapid state of flux (Bourre et al., 1977). Essentially we find that there are no biochemical components present in the CNS, except the DNA, that have a lifetime stability comparable to that required for long-term memory. Since no evidence indicating DNA has been found as yet, it would seem therefore that only the structure and connectivity patterns of the CNS have features with sufficient stability for use in establishing a long-term memory. Such a concept, first proposed in 1893 by Tanzi, reduces the search for the biochemical correlates of memory to the identification of specific physiological, metabolic, and molecular components that can ultimately lead to permanent alterations of neural circuits. These may be processes common to all cells but specially adapted for the CNS, or they may be unique to the CNS requiring specific molecules (Shashoua, 1976). Whether one or both of these types are used, the processes must have the additional property of being controllable by individual cells or parts of cells within the CNS.

Keywords

Sucrose Carbohydrate Cysteine Electrophoresis Fractionation 

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References

  1. Alkon, D. L., 1980, Cellular analysis of a gastropod (Hermissenda crassicornis) model of associative learning, Biol. Bull. 159: 505–560.CrossRefGoogle Scholar
  2. Appel, S. H., 1967, Turnover of brain messenger RNA, Nature (London) 213: 1253–1254.CrossRefGoogle Scholar
  3. Benowitz, L. I. and Shashoua, V. E., 1977, Localization of a brain protein metabolically linked with behavioral plasticity in the goldfish, Brain Res. 136: 227–242.PubMedCrossRefGoogle Scholar
  4. Bliss, T. V. P. and Lømo, T., 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path, J. Physiol. (London) 232: 331–356.Google Scholar
  5. Bonner-Frazer, M. and Cohen, A. M., 1980, Analysis of the neural Crest ventral pathway using injected tracer cells, Dev. Biol. 77: 130–141.CrossRefGoogle Scholar
  6. Bourre, J. M., Pollet, S., Paturneau-Jovas, M., and Baumann, N., 1977, Function and biosynthesis of lipids, Adv. Exp. Med. Biol. 83: 103–109.PubMedGoogle Scholar
  7. Chaffee, J. and Schachner, M., 1978, A new cell-surface antigen of brain kidney and spermatozoa, Dev. Biol. 62: 173–184.PubMedCrossRefGoogle Scholar
  8. Carew, T. L., Walters, E. T., and Kandel, E. R., 1981, Associative learning in Aplysia: Cellular correlates supporting a conditioned fear hypothesis, Science 211: 501–504.PubMedCrossRefGoogle Scholar
  9. Clarke, J. T., 1967, Simplified “disc” (polyacrylamide gel) electrophoresis, Ann. N. Y. Acad. Sci. 121: 428–436.CrossRefGoogle Scholar
  10. Coons, A. H., 1968, Fluorescent antibody methods, in: General Cytological Methods ( J. F. Danielle, ed.), Academic Press, New York, pp. 399–422.Google Scholar
  11. Cragg, B., 1980, Preservation of extracellular space during fixation of the brain for electron microscopy, Tissue Cell 12: 63–72.PubMedCrossRefGoogle Scholar
  12. Cserr, H. F. and Ostrach, L. H., 1974, On the presence of subarachnoid fluid in the mudpuppy, Necturus maculosus, Comp. Biochem. Physiol. 48A: 145–151.CrossRefGoogle Scholar
  13. Duffy, C., Teyler, T. J., and Shashoua, V. E., 1981, Long-term potentiation in the hippocampal slice: Evidence for stimulated secretion of newly synthesized proteins, Science 212: 1145–1151.CrossRefGoogle Scholar
  14. Greene, E., Stauff, C., and Walters, J., 1972, Recovery of function with two-stage lesion of the fornix, Exp. Neurol. 37: 14–22.PubMedCrossRefGoogle Scholar
  15. Hartman, B. K., 1973, Immunofluorescence of dopamaine (β-hydroxylase. Application of improved methodology to the localization of the peripheral and central noradrenergic nervous system, J. Histochem. Cytochem. 21: 312–332.PubMedCrossRefGoogle Scholar
  16. Hesse, G., Hofstein, R., and Shashoua, V. E., 1984, Protein release from hippocampus in vitro, Brain Res. 305: 61–66.PubMedCrossRefGoogle Scholar
  17. Hofstein, R., Hesse, G., and Shashoua, V. E., 1983, Protein of the extracellular fluid of mouse brain: Extraction and partial characterization, J. Neurochem. 40: 1448–1455.PubMedCrossRefGoogle Scholar
  18. King, G. L. and Somjen, G. G., 1981, Extracellular calcium and action potentials of soma and dendrites of hippocampal pyramidal cells, Brain Res. 226: 339–344.PubMedCrossRefGoogle Scholar
  19. Krnjevic, K., Morris, M. E., and Reiffenstein, R. J., 1982a, Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat’s hippocampus, Can. J. Physiol. Pharmacol. 60: 1643–1657.PubMedCrossRefGoogle Scholar
  20. Krnjevic, K., Morris, M. E., Reiffenstein, R. J., and Ropert, N., 1982b, Depth distribution and mechanism of changes in extracellular K+ and Ca2+ concentrations in the hippocampus, Can. J. Physiol. Pharmacol. 60: 1658 - 1671.PubMedCrossRefGoogle Scholar
  21. Lajtha, A. and Toth, J., 1966, Instability of cerebral proteins, J. Biochem. Biophys. Res. Commun. 23: 249–299.CrossRefGoogle Scholar
  22. Lynch, G. S. and Schubert, P., 1980, The use of in vitro brain slices for multidisciplinary studies of synaptic function, Annu. Rev. Neurosci. 3: 1–22.PubMedCrossRefGoogle Scholar
  23. Laemmli, U. K., 1970, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227: 680–685.PubMedCrossRefGoogle Scholar
  24. McCormick, D. A., Clark, G. A., Lavond, D. G., and Thompson, R. F., 1982, Initial localization of the memory trace for a basic form of learning, Proc. Natl. Acad. Sci. USA 79: 2731–2735.PubMedCrossRefGoogle Scholar
  25. McMahan, V. J., Edgington, D. R., and Kuffler, D. P., 1980, Factors that influence regeneration of the neuromuscular junction, J. Expt. Biol. 89: 31–38.Google Scholar
  26. Majocha, R. E., Schmidt, R., and Shashoua, V. E., 1982, Cultures of zona ependyma cells of goldfish brain: An immunological study of the synthesis and release of ependymins, J. Neurosci. Res. 8: 331–342.PubMedCrossRefGoogle Scholar
  27. Reinhold, V. N., 1972, Gas-liquid chromatograpahic analysis of constituent carbohydrates in glyco-proteins, in: Methods of Enzymology, Volume 25 ( C. H. Hirs and S.N. Timasheff, eds.), Academic Press, New York, pp. 244–249.Google Scholar
  28. Sanes, J. R., 1983, Roles of extracellular matrix in neural development, Ann. Rev. Physiol. 45: 581–600.CrossRefGoogle Scholar
  29. Schmidt, R. and Shashoua, V. E., 1981, A radioimunoassay for ependymins P and 7: Two goldfish brain proteins involved in behavioral plasticity, J. Neurochem. 36: 1368–1377.PubMedCrossRefGoogle Scholar
  30. Schmidt, R. and Shashoua, V. E., 1983, Structural and metabolic relationships between goldfish brain glycoproteins participating in functional plasticity of the central nervous system, J. Neurochem. 40: 652–660.PubMedCrossRefGoogle Scholar
  31. Schwartzkroin, P. A. and Wester, K., 1975, Long-lasting facilitation of a synaptic potential following tetanization in the in vitro hiippocampal slice, Brain Res. 89: 107–119.PubMedCrossRefGoogle Scholar
  32. Shashoua, V. E., 1968, RNA changes in goldfish brain during learning, Nature (London) 217: 238–240.CrossRefGoogle Scholar
  33. Shashoua, V. E., 1976, Brain metabolism and the acquisition of new behaviors. I. Evidence for specific changes in the pattern of protein synthesis, Brain Res. 111: 347–367.PubMedCrossRefGoogle Scholar
  34. Shashoua, V. E., 1977a, Brain metabolism and the acquisition of new behaviors. II. Immunological studies of the a, 0 and 7 proteins of goldfish brain, Brain Res. 122: 113–124.PubMedCrossRefGoogle Scholar
  35. Shashoua, V. E., 1977b, Brain protein metabolism and the acquisition of new patterns of behavior, Proc. Natl. Acad. Sci. USA 74: 1743–1747.PubMedCrossRefGoogle Scholar
  36. Shashoua, V. E., 1979, Brain metabolism and the acquisition of new behaviors. III. Evidence for secretion of two proteins into the brain extracellular fluid after training, Brain Res. 166: 349–358.PubMedCrossRefGoogle Scholar
  37. Shashoua, V. E., 1981, Extracellular fluid proteins of goldfish brain: Studies of concentration and labeling patterns, Neurochem. Res. 6 (10): 1129–1147.PubMedCrossRefGoogle Scholar
  38. Shashoua, V. E ., 1982, Molecular and cell biological aspects of learning: Towards a theory of memory, Adv. in Cell. Neurobiol. 3:97–141.Google Scholar
  39. Shashoua, V. E., 1984, The role of extracellular glycoproteins in CNS plasticity: Calcium effects on polymerization, Soc. Neurosci. 10: 195. 12.Google Scholar
  40. Shashoua, V. E., 1985, The role of brain extracellular proteins in neuroplasticity and learning, Cell. Molec. Neurobiol. 5: 183–206.PubMedCrossRefGoogle Scholar
  41. Shashoua, V. E. and Hesse, G., 1985, Role of brain extracellular proteins in the mechanism of long- term potentiation in rat brain hippocampus, Soc. Neurosci. 11: 225. 19.Google Scholar
  42. Shashoua, V. E. and Moore, M. E., 1978, Effect of antisera to £ and 7 goldfish brain proteins on the retention of a newly acquired behavior, Brain Res. 148: 441–449.PubMedCrossRefGoogle Scholar
  43. Shashoua, V. E. and Moore, M. E., 1980, Enhanced labeling of ECF proteins in mouse brain after training, Neurosci. Abstr. 6: 290. 4.Google Scholar
  44. Shashoua, V. E. and Hesse, G., 1985, Role fo brain extracellular proteins in the mechanism of long- term potentiation in rat brain hippocampus, Soc. Neurosci. 11: 225. 19.Google Scholar
  45. Sternberger, L. A., 1979, Immunocytochemistry, J. Wiley & Sons, New York.Google Scholar
  46. Tanzi, E., 1893, Nel’odierna istologia de sistema nervoso, Riv. Sper. Freniatr. Med. Leg. 19: Alienazioni Ment. 419–472.Google Scholar
  47. Teyler, T. J., Lewis, D., and Shashoua, V. E., 1981, Neurophysiological and biochemical properties of the goldfish optic tectum maintained in vitro, Brain Res. Bull. 7: 45–56.PubMedCrossRefGoogle Scholar
  48. Teyler, T. J., 1980, Brain slice preparation: Hippocampus, Brain Res. Bull. 5: 391–403.PubMedCrossRefGoogle Scholar
  49. Thompson, R. F., Berger, T. W., and Madden, J., IV, 1983, Cellular processes of learning and memory in the mammalian CNS, Ann. Rev. Neuroscience 6: 447–492.CrossRefGoogle Scholar
  50. Whittaker, V. P., 1959, The isolation and characterization of acetylcholine particles from brain, Biochem. J. 72: 694–706.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Victor E. Shashoua
    • 1
  1. 1.Mailman Research CenterMcLean Hospital, Harvard Medical SchoolBelmontUSA

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