Advertisement

Role of excitatory amino acid neurotransmission in synaptic plasticity and pathology. An integrative hypothesis concerning the pathogenesis and evolutionary advantages of schizophrenia-related genes

  • P. Etienne
  • M. Baudry
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 29)

Summary

N-methyl-D-aspartate (NMDA) receptors are involved in long-term potentiation, burst firing and the generation of patterned activity in neuronal networks; in use-dependent stabilization of synaptic connectivity in developing animals; in some forms of learning in mature animals; and in pathologies as found in brain aging. A number of these characteristics are reminiscent of several manifestations of schizophrenia and therefore we present the hypothesis that one of the genes modified in schizophrenia is directly or indirectly linked to the control of excitatory neurotransmission; possibly the normal switching on of the expression of the adult form of the NMDA receptor is delayed. Alternatively the adult form of the NMDA receptor is altered, resulting in inappropriate functioning of this receptor. The delayed or faulty expression of the adult form of the NMDA receptor, in turn, should confer a series of evolutionary advantages including protection against aging-associated brain pathologies.

Keywords

NMDA Receptor Brain Aging Adult Form NMDA Receptor Agonist Excitatory Amino Acid Neurotransmission 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anis N, Berry S, Burton R, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of neonatal mammalian neurones by N-methyl-D-aspartate. Br J Pharmacol 79: 565.PubMedGoogle Scholar
  2. Anthony EJ (1969) A clinical evaluation of children with psychotic parents. In: Chess S, Thomas A (eds) Annual progress in child psychiatry and child development. Brunner/ Mazel, New York.Google Scholar
  3. Barnes C (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol 93: 74–103.PubMedCrossRefGoogle Scholar
  4. Baudry M, Bundman MO, Smith EK, Lych G (1981) Micromolar levels of calcium stimulates proteolytic activity and glutamate binding in rat synaptic membranes. Science 212: 937–938.PubMedCrossRefGoogle Scholar
  5. Baudry M, Evans J, Lynch G (1986) Excitatory amino acids inhibit stimulation of phos-phatidylinositol metabolism by aminergic agonists in hippocampus. Nature 319: 329–331.PubMedCrossRefGoogle Scholar
  6. Baudry M, Larson J, Lynch G (1987) Long-term changes in synaptic efficacy: potential mechanisms and implications. In: Landfield P, Deadwyler S (eds) Long-term poten-tiation: mechanisms and key issues. Alan R Liss, New York, pp 107–135.Google Scholar
  7. Ben-Ari Y, Cherubini E, Krnjevic K (1988) Changes in voltage dependence of NMDA currents during development. Neurosci Lett 94: 88–92.PubMedCrossRefGoogle Scholar
  8. Blessed G, Tomlinson BE, Roth M (1983) The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 114: 797–811.CrossRefGoogle Scholar
  9. Bliss TVP, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol (Lond) 232: 331–356.Google Scholar
  10. Bliss TVP, Gardner-Medwin AT (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path. J Physiol (Lond) 232: 357–374.Google Scholar
  11. Bogerts B, Meertz E, Schönfeldt-Bausch R (1985) Basal ganglia and limbic system pathology in schizophrenia. A morphological study of brain volume and shrinkage. Arch Gen Psychiatry 42: 784–791.PubMedCrossRefGoogle Scholar
  12. Carlin RK, Bartelt DC, Siekevitz P (1983) Identification of fodrin as a major calmodulin-binding protein in postsynaptic density preparations. J Cell Biol 96: 443–448.PubMedCrossRefGoogle Scholar
  13. Cline H, Debski E, Constantine-Paton M (1987) N-methyl-D-aspartate receptors antagoist desegregates eye-specific stripes. Proc Natl Acad Sci 84: 4342–4345.PubMedCrossRefGoogle Scholar
  14. Collingridge G, Bliss T (1987) NMDA receptors-their role in long term potentiation. Trends Neurosci 10: 288–293.CrossRefGoogle Scholar
  15. Colquhoun D (1986) Structure and function of acetylcholine-receptor ion channels. Nature 321: 382–383.PubMedCrossRefGoogle Scholar
  16. Davis K, Berger P, Hollinger L (1976) Tardive dyskinesia and depressive illness. Psycho-pharmacol Commun 2: 125–130.Google Scholar
  17. Dougls R, Goddard G (1975) Long-term potentiation of the performant path-granule cell synapse in the rat hippocampus. Brain Res 86: 205–215.CrossRefGoogle Scholar
  18. Etienne P, Baudry M (1987) Calcium-dependent aspects of synaptic plasticity, excitatory amino acid neurotransmission, brain aging and schizophrenia: a unifying hypothesis. Neurobiol Aging 8: 362–366.PubMedCrossRefGoogle Scholar
  19. Feinberg I (1982) Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res (England) 17: 319–334.CrossRefGoogle Scholar
  20. Huttenlocher P (1979) Synaptic density in human frontal cortex; developmental changes and effects of aging. Brain Res 163: 195–205.PubMedCrossRefGoogle Scholar
  21. Huttenlocher P, de Courten C, Garey L, Van der Loos H (1982) Synaptogenesis in human visual cortex; evidence for synapse elimination during normal development. Neurosci Lett 3: 247–252.CrossRefGoogle Scholar
  22. Johnson JW, Ascher P (1987) Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 325: 529–531.PubMedCrossRefGoogle Scholar
  23. Karlsson J (1973) An icelandic family study of schizophrenia. Br J Psychiatry 123: 549–554.PubMedCrossRefGoogle Scholar
  24. Karlsson J (1982) Family transmission of schizophrenia: a review and synopsis. Br J Psychiatry 140: 600–606.PubMedCrossRefGoogle Scholar
  25. Karlsson J (1978) Inheritance and creative intelligence. Nelson-Hall, Chicago.Google Scholar
  26. Kessler M, Baudry M, Lynch G (1987) Use of cystine to distinguish glutamate binding from glutamate sequestration. Neurosci Lett 81: 221–226.PubMedCrossRefGoogle Scholar
  27. Khatchaturian ZS (1984) Toward theories of brain aging. In: Kaye I, Burrows E (eds) Handbook of studies on psychiatry and old age, pp 157-194.Google Scholar
  28. Kim JS, Kornhuber HH, Schmid-Burgk W, Holzmüller R (1980) Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis of schizophrenia. Neurosci Lett 20: 379–382.PubMedCrossRefGoogle Scholar
  29. Kleinschmidt A, Bear MF, Singer W (1987) Blockade of “NMDA” receptors disrupts experience-dependent plasticity of kitten striate cortex. Science 238: 355–358.PubMedCrossRefGoogle Scholar
  30. Kovelman JA, Scheibel AB (1984) A neurohistological correlate of schizophrenia. Biol Psychiatry 19: 1601–1621.PubMedGoogle Scholar
  31. Lander ES (1988) Splitting schizophrenia. Nature 336: 105–106.PubMedCrossRefGoogle Scholar
  32. Lange-Eichbaum W (1931) The problem of genius. Kegan Paul, Trench, Trubner, London.Google Scholar
  33. Larson J, Lynch G (1986) Induction of synaptic potentiation in hippocampus by patterned stimulation involves two events. Science 232: 985–988.PubMedCrossRefGoogle Scholar
  34. Larson J, Wong D, Lynch G (1986) Patterned stimulation at the theta frequency is optimal for induction of long-term potentiation. Brain Res 368 (3): 347–350.PubMedCrossRefGoogle Scholar
  35. Lynch G, Baudry M (1984) The biochemistry of memory: a new and specific hypothesis. Science 224: 1057–1063.PubMedCrossRefGoogle Scholar
  36. Lynch G, Bodsch W, Baudry M (1988) Cytoskeletal protein and the regulation of synaptic structure. In: Lasek RJ, Block MM (eds) Intrinsic determinants of neuronal form. Alan R Liss, pp 217-243.Google Scholar
  37. Lynch G, Halpain S, Baudry M (1982) Effects of high a frequency stimulation on glutamate receptor binding studied with a modified in vitro hippocampal slice reparation. Brain Res 244: 101–111.PubMedCrossRefGoogle Scholar
  38. McDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker JL (1986) NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones. Nature 321: 519–522.CrossRefGoogle Scholar
  39. McGeer PL (1984) Aging, Alzheimer’s disease, and the cholinergic system. J Physiol Pharmacol (Can) 62: 741–754.CrossRefGoogle Scholar
  40. McGeer PL, McGeer EG (1977) Possible changes in striatal and limbic cholinergic systems in schizophrenia. Arch Gen Psychiatry 334: 1319–1323.CrossRefGoogle Scholar
  41. Mattson P, Kater SB (1989) Excitatory and inhibitory neurotransmitters in the generation and degeneration of hippocampal neuroarchitecture. Brain Res 478: 337–348.PubMedCrossRefGoogle Scholar
  42. Mayer ML, Westbrook GL, Guthrie PB (1984) Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature 309: 261–263.PubMedCrossRefGoogle Scholar
  43. Mishina M, Takai T, Imoto K, Noda M, Takahashi T, Numa S (1986) Methfessel C and Sakmann B Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature 321: 406–411.PubMedCrossRefGoogle Scholar
  44. Nicoletti F, Ladarola MJ, Wroblewski JT, Costa E (1986) Excitatory amino acid recognition sites coupled with inositol phospholipid metabolism: developmental changes and interaction with alpha-1 adrenoreceptors. Proc Natl Acad Sci USA 83: 1931–1935.PubMedCrossRefGoogle Scholar
  45. Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A (1984) Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307: 462–465.PubMedCrossRefGoogle Scholar
  46. Rakic P, Bourgeois JP, Eckenhoff MF, Zecevic N, Goldman-Rakic PS (1986) Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex. Science 232: 232–235.PubMedCrossRefGoogle Scholar
  47. Rauscheker J, Hahn S (1987) Ketamine-xylazine anaesthesia blocks consolidation of ocular dominance changes in kitten visual cortex. Nature 326: 183–185.CrossRefGoogle Scholar
  48. Routter JI, Diamond JM (1987) What maintains the frequencies of human genetic diseases? Nature 329: 289–290.CrossRefGoogle Scholar
  49. Seubert P, Baudry M, Dudek S, Lynch G (1987) Calmodulin stimulates the degradation of brain spectrin by calpain. Synapse 1: 20–24.PubMedCrossRefGoogle Scholar
  50. Seubert P, Larson J, Oliver M, Jung M, Baudry M, Lynch G (1988) Stimulation of NMDA receptors induces proteolysis of spectrin in hippocampus. Brain Res 460: 189–194.PubMedCrossRefGoogle Scholar
  51. Siman R, Baudry M, Lynch G (1985) Glutamate receptor regulation by proteolysis of the cytoskeletal protein fodrin. Nature 315: 225–227.CrossRefGoogle Scholar
  52. Siman R, Baudry M, Lynch G (1987) Calcium-activated proteases as possible mediators of synaptic plasticity. In: Edelman G, Gall W, Cowan WM (eds) Synaptic function. John Wiley & Sons, pp 519-548.Google Scholar
  53. Staubli U, Lynch G (1987) Stable hippocampal long-term potentiation elicited by “theta” pattern stimulation. Brain Res 435: 227–234.PubMedCrossRefGoogle Scholar
  54. Staubli U, Larson J, Baudry M, Thibault O, Lynch G (1988) Chronic administration of a thiol-proteinase inhibitor blocks long-term potentiation of synaptic responses. Brain Res 444: 153–158.PubMedCrossRefGoogle Scholar
  55. Stevens J (1982) Neuropathology of schizophrenia. Arch Gen Psychiatry 39: 1131–1139.PubMedCrossRefGoogle Scholar
  56. Tsumoto T, Hagihara K, Sato H, Hata Y (1987) NMDA receptors in the visual cortex of young kittens are more effective than those of adult cats. Nature 327: 513–514.PubMedCrossRefGoogle Scholar
  57. Vargas F, Greenbaum L, Costa E (1980) Participation of a cysteine proteinase in the high affinity Ca2+ dependent binding of glutamate to hippocampal synaptic membranes. Neuropharmacology 19: 791.PubMedCrossRefGoogle Scholar
  58. Wigstrom H, Gustafsson B (1985) On long-lasting potentiation in the hippocampus: a proposed mechanism for its dependence on coincident pre-and post-synaptic activity. Acta Physiol Scand 123: 519–522.PubMedCrossRefGoogle Scholar
  59. Wong D, Wagner H, Tune L, Dannals R, Pearlson G, Links J, Tamminga C, Broussolle E, Ravert H, Wilson A, Toung T, Malat J, Williams J, O’Tuama L, Snyder S, Kuhar M, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234: 1558–1563.PubMedCrossRefGoogle Scholar
  60. Yassa R, Nair V, Schwartz G (1984) Tardive dyskinesia and the primary psychiatric diagnosis. Psychosomatics 25: 135–138.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • P. Etienne
    • 1
    • 3
  • M. Baudry
    • 2
  1. 1.Department of PsychiatryMcGill UniversityMontrealCanada
  2. 2.Center for the Neurobiology of Learning and Memory IrvineUSA
  3. 3.Allan Memorial InstituteMontrealCanada

Personalised recommendations