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The Role of Brain Extracellular Proteins in Learning and Memory

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Neural Mechanisms of Conditioning
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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.

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References

  • Alkon, D. L., 1980, Cellular analysis of a gastropod (Hermissenda crassicornis) model of associative learning, Biol. Bull. 159: 505–560.

    Article  Google Scholar 

  • Appel, S. H., 1967, Turnover of brain messenger RNA, Nature (London) 213: 1253–1254.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • Bonner-Frazer, M. and Cohen, A. M., 1980, Analysis of the neural Crest ventral pathway using injected tracer cells, Dev. Biol. 77: 130–141.

    Article  Google Scholar 

  • Bourre, J. M., Pollet, S., Paturneau-Jovas, M., and Baumann, N., 1977, Function and biosynthesis of lipids, Adv. Exp. Med. Biol. 83: 103–109.

    PubMed  CAS  Google Scholar 

  • Chaffee, J. and Schachner, M., 1978, A new cell-surface antigen of brain kidney and spermatozoa, Dev. Biol. 62: 173–184.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, J. T., 1967, Simplified “disc” (polyacrylamide gel) electrophoresis, Ann. N. Y. Acad. Sci. 121: 428–436.

    Article  Google Scholar 

  • Coons, A. H., 1968, Fluorescent antibody methods, in: General Cytological Methods ( J. F. Danielle, ed.), Academic Press, New York, pp. 399–422.

    Google Scholar 

  • Cragg, B., 1980, Preservation of extracellular space during fixation of the brain for electron microscopy, Tissue Cell 12: 63–72.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  Google Scholar 

  • Greene, E., Stauff, C., and Walters, J., 1972, Recovery of function with two-stage lesion of the fornix, Exp. Neurol. 37: 14–22.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Hesse, G., Hofstein, R., and Shashoua, V. E., 1984, Protein release from hippocampus in vitro, Brain Res. 305: 61–66.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Lajtha, A. and Toth, J., 1966, Instability of cerebral proteins, J. Biochem. Biophys. Res. Commun. 23: 249–299.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Laemmli, U. K., 1970, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature 227: 680–685.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Sanes, J. R., 1983, Roles of extracellular matrix in neural development, Ann. Rev. Physiol. 45: 581–600.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Shashoua, V. E., 1968, RNA changes in goldfish brain during learning, Nature (London) 217: 238–240.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Shashoua, V. E., 1977b, Brain protein metabolism and the acquisition of new patterns of behavior, Proc. Natl. Acad. Sci. USA 74: 1743–1747.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Shashoua, V. E., 1981, Extracellular fluid proteins of goldfish brain: Studies of concentration and labeling patterns, Neurochem. Res. 6 (10): 1129–1147.

    Article  PubMed  CAS  Google Scholar 

  • Shashoua, V. E ., 1982, Molecular and cell biological aspects of learning: Towards a theory of memory, Adv. in Cell. Neurobiol. 3:97–141.

    CAS  Google Scholar 

  • Shashoua, V. E., 1984, The role of extracellular glycoproteins in CNS plasticity: Calcium effects on polymerization, Soc. Neurosci. 10: 195. 12.

    Google Scholar 

  • Shashoua, V. E., 1985, The role of brain extracellular proteins in neuroplasticity and learning, Cell. Molec. Neurobiol. 5: 183–206.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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 

  • Sternberger, L. A., 1979, Immunocytochemistry, J. Wiley & Sons, New York.

    Google Scholar 

  • Tanzi, E., 1893, Nel’odierna istologia de sistema nervoso, Riv. Sper. Freniatr. Med. Leg. 19: Alienazioni Ment. 419–472.

    Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Teyler, T. J., 1980, Brain slice preparation: Hippocampus, Brain Res. Bull. 5: 391–403.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Whittaker, V. P., 1959, The isolation and characterization of acetylcholine particles from brain, Biochem. J. 72: 694–706.

    PubMed  CAS  Google Scholar 

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© 1986 Plenum Press, New York

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Shashoua, V.E. (1986). The Role of Brain Extracellular Proteins in Learning and Memory. In: Alkon, D.L., Woody, C.D. (eds) Neural Mechanisms of Conditioning. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2115-6_31

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  • DOI: https://doi.org/10.1007/978-1-4613-2115-6_31

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9251-7

  • Online ISBN: 978-1-4613-2115-6

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