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The Role of Glutamate in Neurotransmission and in Neurologic Disease

The Role of Glutamate in Neurotransmission and in Neurologic Disease Abstract • Glutamate is the putative neurotransmitter of several clinically important pathways, including cortical association fibers, corticofugal pathways such as the pyramidal tract, and hippocampal, cerebellar, and spinal cord pathways. The excitatory actions of glutamate are mediated by multiple, distinct receptor types and potent receptor antagonists have recently been developed. Glutamate also has neurotoxic properties and can produce "excitotoxic" lesions reminiscent of human neurodegenerative disorders. Abnormally enhanced glutamatergic neurotransmission may cause excitotoxic cell damage and lead to the neuronal death associated with olivopontocerebellar atrophy, Huntington's disease, status epilepticus, hypoxia/ischemia, and hypoglycemia. Pharmacologic manipulation of the glutamatergic system may have great potential for the rational treatment of a variety of neurologic diseases. References 1. Price JC, Waelsch H, Putnam TJ: DL-Glutamic acid hydrochloride in treatment of petit mal and psychomotor seizures . JAMA 1943;122:1153-1156.Crossref 2. Ewalt JR, Bruce EI: Newer concepts of schizophrenia . Texas Rep Biol Med 1948;6:97-107. 3. Albert K, Hoch P, Waelsch H: Preliminary report on the effect of glutamic acid administration in mentally retarded subjects . J Nerv Ment Dis 1946;104:263-274.Crossref 4. Ellson DG, Fuller PR, Urmston R: The influence of glutamic acid on test performance . Science 1950;112:248-250.Crossref 5. Kerr WJ, Szurek SA: Effect of glutamic acid on mental function . Pediatrics 1950;5:645-648. 6. Krebs HA, Eggleston LV, Hems R: Distribution of glutamine and glutamic acid in animal tissues . Biochem J 1949;44:159-163. 7. Lajtha A, Berl S, Waelsch H: Amino acid and protein metabolism of the brain IV: The metabolism of glutamic acid . J Neurochem 1959;3:322-332.Crossref 8. Hayashi T: A physiological study of epileptic seizures following cortical stimulation in animals and its application to human clinics . Jpn J Physiol 1952;3:46-64.Crossref 9. Hayashi T: Effects of sodium glutamate on the nervous system . Keio J Med 1954;3:183-192.Crossref 10. Curtis DR, Watkins JC: The excitation and depression of spinal neurons by structurally related amino acids . J Neurochem 1960;6:117-141.Crossref 11. Watkins JC, Evans RH: Excitatory amino acid transmitters . Annu Rev Pharmacol Toxicol 1981;21:165-204.Crossref 12. Fonnum F: Glutamate: A neurotransmitter in the mammalian brain . J Neurochem 1984;42:1-11.Crossref 13. Lajtha A, Maker HS, Clarke DD: Metabolism and transport of carbohydrates and amino acids , in Siegel G, Albers RW, Agranoff BW, et al (eds): Basic Neurochemistry . Boston, Little Brown & Co, 1981, p 344. 14. Shank RP, Campbell GleM: Glutamate , in Lajtha A (ed): Handbook of Neurochemistry . New York, Plenum Press, 1983, vol 3, pp 381-404. 15. Perry TL, Berry K, Diamond S, et al: Regional distribution of amino acids in human brain obtained at autopsy . J Neurochem 1971;18:513-519.Crossref 16. Fonnum F, Storm-Mathisen J, Divac I: Biochemical evidence for glutamate as a neurotransmitter in corticostriatal and corticothalamic fibers in rat brain . Neuroscience 1981;6:863-873.Crossref 17. Young AB, Oster-Granite ML, Herndon RM, et al: Glutamic acid: Selective depletion by viral-induced granule cell loss in hamster cerebellum . Brain Res 1974;73:1-13.Crossref 18. Storm-Mathisen J, Leknes AK, Bore AT, et al: Glutamate and GABA: First visualization in neurons by immunocytochemistry . Nature 1983;301:517-520.Crossref 19. Naito S, Ueda T: Adenosine triphosphatedependent uptake of glutamate into protein I-associated vesicles . J Biol Chem 1983;258:696-699. 20. Potashner SJ: The spontaneous and electrically-evoked release from slices of guinea-pig cerebral cortex of endogenous amino acids labeled via metabolism of D-[U-14C]glucose . J Neurochem 1978;31:177-186.Crossref 21. De Belleroche JS, Bradford HF: Metabolism of beds of mammalian cortical synaptosomes: Responses to depolarizing influences . J Neurochem 1972;19:525-602.Crossref 22. Hamberger A, Berthold C-H, Karlsson B, et al: Extracellular GABA, glutamate and glutamine in vivo: Perfusion dialysis of the rabbit hippocampus , in Hertz L, Kvamme E, McGeer EG, et al (eds): Glutamine, Glutamate and GABA in the Central Nervous System . New York, Alan R Liss Inc, 1983, pp 473-491. 23. Abdul-Ghani AS, Bradford HF, Cox DWG, et al: Peripheral sensory stimulation and the release of transmitter amino acids in vivo from specific regions of cerebral cortex . Brain Res 1979;171:55-56.Crossref 24. Granata AR, Reis DJ: Release of [3H]Lglutamic acid (L-glu) and [3H]D-aspartic acid (D-asp) in the area of nucleus tractus solitarius in vivo produced by stimulation of the vagus nerve . Brain Res 1983;259:77-93.Crossref 25. Fonnum F, Lund-Karlsen R, Malthe-Sorensen D, et al: High affinity transport systems and their role in transmitter action , in Cotman CW, Poste G, Nicholson GL (eds): The Cell Surface and Neuronal Function . Amsterdam, Elsevier/North Holland Biomedical Press, 1980, pp 455-504. 26. Johnston GAR, Lodge D, Bernstein JC, et al: Potentiation of L-glutamate and L-aspartate excitation of cat spinal neurones by the stereo isomers of threo-3-hydroxyaspartate . J Neurochem 1980;34:241-243.Crossref 27. Henn F, Hamberger A: Glial cell function: Uptake of transmitter substances . Proc Natl Acad Sci USA 1971;68:2686-2690.Crossref 28. Young AB, Penney JB, Dauth GW, et al: Glutamate or aspartate as a possible neurotransmitter of cerebral corticofugal fibers in the monkey . Neurology 1983;33:1513-1516.Crossref 29. Fagg GE, Foster AC: Amino acid neurotransmitters and their pathways in the mammalian central nervous system . Neuroscience 1983;9:701-719.Crossref 30. Davies J, Evans RH, Francis AA, et al: Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system . J Physiol 1980;75:641-645. 31. Fagg GE, Foster AC, Mena EE, et al: Chloride and calcium ions reveal a pharmacologically distinct population of L-glutamate binding sites in synaptic membranes: Correspondence between biochemical and electrophysiological data . J Neurosci 1982;2:958-965. 32. Davies J, Evans RH, Jones AW, et al: Recent advances in the pharmacology of excitatory amino acids in the mammalian central nervous system , in Fuxe K, Roberts PJ, Schwarcz R (eds): Excitotoxins . New York, Macmillan Publishing Co Inc, 1983, pp 43-54. 33. Thomson AM, West DC, Lodge D: An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamaine? Nature 1985;313:479-481.Crossref 34. Crepel F, Dhanjal SS, Sears TA: Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje cell dendrites in the rat: An in vitro study . J Physiol 1982;329:297-317. 35. Koerner JF, Cotman CW: Micromolar L-2-amino-4-phosphonobutyric acid selectively inhibits perforant path synapses from lateral entorhinal cortex . Brain Res 1981;216:192-198.Crossref 36. Harris EW, Ganong AH, Cotman CW: Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors . Brain Res 1984;323:132-137.Crossref 37. Collingridge GL, Kehl SJ, McLennan H: Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus . J Physiol 1983;334:33-46. 38. Foster AC, Fagg GE: Acidic amino acid binding sites in mammalian neuronal membranes: Their characteristics and relationship to synaptic receptors . Brain Res Rev 1984;7:103-164.Crossref 39. Fagg GE, Matus A: Selective association of N-methyl-D-aspartate and quisqualate types of L-glutamate receptor with brain postsynaptic densities . Proc Natl Acad Sci USA 1984;81:6876-6880.Crossref 40. Monaghan DT, Holets VR, Toy DR, et al: Anatomical distributions of four pharmacologically distinct 3H-L-glutamate binding sites . Nature 1983;306:176-179.Crossref 41. Greenamyre JT, Olson JMM, Penney JB, et al: Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate- and kaina tesensitive glutamate binding sites . J Pharmacol Exp Ther 1985;233:254-263. 42. Greenamyre JT, Young AB, Penney JB: Quantitative autoradiographic distribution of L-[3H]glutamate binding sites in rat central nervous system . J Neurosci 1984;4:2133-2144. 43. Halpain SH, Wieczorek CM, Rainbow TC: Localization of L-glutamate receptors in rat brain by quantitative autoradiography . J Neurosci 1984;4:2247-2258. 44. Greenamyre JT, Penney JB, Young AB, et al: Alterations in L-[3H]glutamate binding in Alzheimer's and Huntington's diseases . Science 1985;227:1496-1499.Crossref 45. Greenamyre JT, Penney JB, Young AB, et al: Evidence for transient, perinatal, glutamatergic innervation of globus pallidus. J Neurosci, in press. 46. Lucas DR, Newhouse JP: The toxic effect of sodium L-glutamate on the inner layers of the retina . Arch Ophthalmol 1957;58:193-204.Crossref 47. Olney JW: Glutamate-induced neuronal necrosis in the infant mouse hypothalamus: An electron microscopic study . J Neuropathol Exp Neurol 1971;30:75-90.Crossref 48. Olney JW, Ho OL, Rhee V: Cytotoxic effects of acidic and sulphur containing amino acids on the infant mouse central nervous system . Exp Brain Res 1971;14:61-76.Crossref 49. Olney JW, Fuller T, DeGubareff T: Acute dendrotoxic changes in the hippocampus of kainate-treated rats . Brain Res 1979;176:91-100.Crossref 50. Evans MC, Griffiths T, Meldrum BS: Early hippocampal changes in the rat following bicuculline and L-allylglycine-induced seizures: A light and electron microscope study . Neuropathol Appl Neurobiol 1983;9:39-52.Crossref 51. Fuxe K, Roberts P, Schwarcz R (eds): Excitotoxins . New York, Macmillan Publishing Co Inc, 1983. 52. Mangano RM, Schwarcz R: Chronic infusion of endogenous excitatory amino acids into rat striatum and hippocampus . Brain Res Bull 1983;10:47-51.Crossref 53. Kohler C, Schwarcz R: Monosodium glutamate: Increased neurotoxicity after removal of neuronal re-uptake sites . Brain Res 1981;211:485-491.Crossref 54. McBean GJ, Roberts PJ: Neurotoxicity of L-glutamate and DL-threo-3-hydroxyaspartate in the rat striatum . J Neurochem 1985;44:247-254.Crossref 55. Schwarcz R, Scholz D, Coyle JT: Structure activity relations for the neurotoxicity of kainic acid derivatives and glutamate analogues . Neuropharmacology 1978;17:145-151.Crossref 56. Coyle JT: Neurotoxic action of kainic acid . J Neurochem 1983;41:1-11.Crossref 57. Simon RP, Griffiths T, Evans MC, et al: Calcium overload in selectively vulnerable neurons of the hippocampus during and after ischemia: An EM study in the rat . J Cereb Blood Flow Metab 1984;4:350-361.Crossref 58. Griffiths T, Evans MC, Meldrum BS: Temporal lobe epilepsy, excitotoxins and the mechanism of selective neuronal loss , in Fuxe K, Roberts P, Schwarcz R (eds): Excitotoxins . New York, Macmillan Publishing Co Inc, 1983, pp 331-342. 59. Rothman SM: The neurotoxicity of excitatory amino acids is produced by passive chloride influx . J Neurosci 1985;5:1483-1489. 60. Coyle JT, Schwarcz R: Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea . Nature 1976;263:244-246.Crossref 61. McGeer EG, McGeer PL: Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids . Nature 1976;263:517-519.Crossref 62. Schwarcz R, Coyle JT: Striatal lesions with kainic acid: Neurochemical characteristics . Brain Res 1977;127:235-249.Crossref 63. Coyle JT, Molliver ME, Kuhar MJ: Morphological analysis of kainic acid lesion of rat striatum . J Comp Neurol 1978;180:301-324.Crossref 64. Hruska RE, Silbergeld EK: Abnormal locomotion in rats after bilateral intrastriatal injections of kainic acid . Life Sci 1979;25:181-194.Crossref 65. Divac I, Markowitsch HJ, Pritzel M: Behavioral and anatomic consequences of small intrastriatal injections of kainic acid in the rat . Brain Res 1978;151:523-532.Crossref 66. Sanberg PR, Fibiger HC: Body weight, feeding and drinking behaviors in rats with kainic acid-induced lesions of striatal neurons: With a note on body weight symptomatology in Huntington's disease . Exp Neurol 1979;66:444-466.Crossref 67. Bradford HF, Dodd PR: Convulsions and activation of epileptic foci induced by monosodium glutamate and related compounds . Biochem Pharmacol 1975;26:253-254.Crossref 68. Lambert JDC, Flatman JA, Engberg I: Actions of excitatory amino acids on membrane conductance and potential in motoneurons . Adv Biochem Psychopharmacol 1981;27:205-216. 69. Sloviter RS: Epileptic brain damage in rats induced by sustained electrical stimulation of the perforant path: I. Acute electrophysiological and light microscopic studies . Brain Res Bull 1983;10:675-697.Crossref 70. Sloviter RS, Dempster DW: 'Epileptic' brain damage is replicated qualitatively in the rat hippocampus by central injection of glutamate or aspartate but not by GABA or acetylcholine . Brain Res Bull 1985;15:39-60.Crossref 71. Savage DD, Werling LL, Nadler V, et al: Selective increase in L-[3H]glutamate binding to a quisqualate sensitive site on hippocampal membranes after angular bundle kindling . Eur J Pharmacol 1982;85:255-256.Crossref 72. Schwarcz R, Meldrum B: Excitatory aminoacid antagonists provide a therapeutic approach to neurological disorders . Lancet 1985;2:140-143.Crossref 73. Benveniste H, Drejer J, Schousboe A, et al: Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis . J Neurochem 1984;43:1369-1374.Crossref 74. Silverstein FS, Buchanon K, Johnston MV: Hypoxia-ischemia causes severe but reversible depression of striatal synaptosomal 3H-glutamate uptake . Ann Neurol 1985;18:122. 75. Brierly JB, Graham DI: Hypoxia and vascular disorders of the central nervous system , in Adams JH, Corsellis JAN, Duchen LW (eds): Greenfield's Neuropathology . New York, John Wiley & Sons Inc, 1984, pp 125-207. 76. Simon RP, Swan JH, Griffiths T, et al: Blockage of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain . Science 1984;226:850-852.Crossref 77. Rothman S: Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death . J Neurosci 1984;4:1884-1891. 78. Wieloch T: Endogenous excitotoxins as possible mediators of ischemic and hypoglycemic brain damage . Epilepsia 1985;26:501. 79. Laroche JC: Perinatal brain damage , in Adams JH, Corsellis JAN, Duchen LW (eds): Greenfield's Neuropathology , New York, John Wiley & Sons Inc, 1984, pp 451-490. 80. Plaitakis A, Berl S, Yahr M: Abnormal glutamate metabolism in an adult-onset degenerative neurological disorder . Science 1982;216:193-196.Crossref 81. Wieloch T: Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist . Science 1985;230:681-683.Crossref 82. Wurtman RJ, Corkin SH, Growdon JH (eds): Alzheimer's Disease: Advances in Basic Research and Therapies . Cambridge, Mass, Center for Brain Sciences and Metabolism Charitable Trust, 1984, p 482. 83. Sofroniew MV, Pearson RCA, Eckenstein F, et al: Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage . Brain Res 1983;289:370-374.Crossref 84. Sofroniew MV, Pearson RCA: Degeneration of cholinergic neurons in the basal nucleus following kainic or N-methyl-D-aspartic acid application to the cerebral cortex in the rat . Brain Res 1985;339:186-190.Crossref 85. DeBoni U, Crapper-McLachlan DR: Controlled induction of paired helical filaments of the Alzheimer type in cultured human neurons, by glutamate and aspartate . J Neurol Sci 1985;68:105-118.Crossref 86. Greenamyre JT, Young AB, Penney JB, et al: A selective loss of glutamate receptors in hippocampus of Alzheimer's disease . Neurology 1985;35:S183. 87. Hyman BT, VanHoesen GW, Damasio AR, et al: Alzheimer's disease: Cell-specific pathology isolates the hippocampal formation . Science 1984;225:1168-1170.Crossref 88. Rogers J, Morrison JH: Quantitative morphology and regional laminar distributions of senile plaques in Alzheimer's disease . J Neurosci 1985;5:2801-2808. 89. 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Maragos WF, Chu DCM, Greenamyre JT, et al: High correlation between the localization of [3H]TCP binding and NMDA receptors . Eur J Pharmacol 1986;123:173-174.Crossref 106. Rothman S: Glutamate and anoxic neuronal death in vitro . Epilepsia 1985;5:515. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

The Role of Glutamate in Neurotransmission and in Neurologic Disease

Archives of Neurology , Volume 43 (10) – Oct 1, 1986

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References (108)

Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1986.00520100062016
Publisher site
See Article on Publisher Site

Abstract

Abstract • Glutamate is the putative neurotransmitter of several clinically important pathways, including cortical association fibers, corticofugal pathways such as the pyramidal tract, and hippocampal, cerebellar, and spinal cord pathways. The excitatory actions of glutamate are mediated by multiple, distinct receptor types and potent receptor antagonists have recently been developed. Glutamate also has neurotoxic properties and can produce "excitotoxic" lesions reminiscent of human neurodegenerative disorders. Abnormally enhanced glutamatergic neurotransmission may cause excitotoxic cell damage and lead to the neuronal death associated with olivopontocerebellar atrophy, Huntington's disease, status epilepticus, hypoxia/ischemia, and hypoglycemia. Pharmacologic manipulation of the glutamatergic system may have great potential for the rational treatment of a variety of neurologic diseases. References 1. Price JC, Waelsch H, Putnam TJ: DL-Glutamic acid hydrochloride in treatment of petit mal and psychomotor seizures . JAMA 1943;122:1153-1156.Crossref 2. Ewalt JR, Bruce EI: Newer concepts of schizophrenia . Texas Rep Biol Med 1948;6:97-107. 3. Albert K, Hoch P, Waelsch H: Preliminary report on the effect of glutamic acid administration in mentally retarded subjects . J Nerv Ment Dis 1946;104:263-274.Crossref 4. Ellson DG, Fuller PR, Urmston R: The influence of glutamic acid on test performance . Science 1950;112:248-250.Crossref 5. Kerr WJ, Szurek SA: Effect of glutamic acid on mental function . Pediatrics 1950;5:645-648. 6. Krebs HA, Eggleston LV, Hems R: Distribution of glutamine and glutamic acid in animal tissues . Biochem J 1949;44:159-163. 7. Lajtha A, Berl S, Waelsch H: Amino acid and protein metabolism of the brain IV: The metabolism of glutamic acid . J Neurochem 1959;3:322-332.Crossref 8. Hayashi T: A physiological study of epileptic seizures following cortical stimulation in animals and its application to human clinics . Jpn J Physiol 1952;3:46-64.Crossref 9. Hayashi T: Effects of sodium glutamate on the nervous system . Keio J Med 1954;3:183-192.Crossref 10. Curtis DR, Watkins JC: The excitation and depression of spinal neurons by structurally related amino acids . J Neurochem 1960;6:117-141.Crossref 11. Watkins JC, Evans RH: Excitatory amino acid transmitters . Annu Rev Pharmacol Toxicol 1981;21:165-204.Crossref 12. Fonnum F: Glutamate: A neurotransmitter in the mammalian brain . J Neurochem 1984;42:1-11.Crossref 13. Lajtha A, Maker HS, Clarke DD: Metabolism and transport of carbohydrates and amino acids , in Siegel G, Albers RW, Agranoff BW, et al (eds): Basic Neurochemistry . Boston, Little Brown & Co, 1981, p 344. 14. Shank RP, Campbell GleM: Glutamate , in Lajtha A (ed): Handbook of Neurochemistry . New York, Plenum Press, 1983, vol 3, pp 381-404. 15. Perry TL, Berry K, Diamond S, et al: Regional distribution of amino acids in human brain obtained at autopsy . J Neurochem 1971;18:513-519.Crossref 16. Fonnum F, Storm-Mathisen J, Divac I: Biochemical evidence for glutamate as a neurotransmitter in corticostriatal and corticothalamic fibers in rat brain . Neuroscience 1981;6:863-873.Crossref 17. Young AB, Oster-Granite ML, Herndon RM, et al: Glutamic acid: Selective depletion by viral-induced granule cell loss in hamster cerebellum . Brain Res 1974;73:1-13.Crossref 18. Storm-Mathisen J, Leknes AK, Bore AT, et al: Glutamate and GABA: First visualization in neurons by immunocytochemistry . Nature 1983;301:517-520.Crossref 19. Naito S, Ueda T: Adenosine triphosphatedependent uptake of glutamate into protein I-associated vesicles . J Biol Chem 1983;258:696-699. 20. Potashner SJ: The spontaneous and electrically-evoked release from slices of guinea-pig cerebral cortex of endogenous amino acids labeled via metabolism of D-[U-14C]glucose . J Neurochem 1978;31:177-186.Crossref 21. De Belleroche JS, Bradford HF: Metabolism of beds of mammalian cortical synaptosomes: Responses to depolarizing influences . J Neurochem 1972;19:525-602.Crossref 22. Hamberger A, Berthold C-H, Karlsson B, et al: Extracellular GABA, glutamate and glutamine in vivo: Perfusion dialysis of the rabbit hippocampus , in Hertz L, Kvamme E, McGeer EG, et al (eds): Glutamine, Glutamate and GABA in the Central Nervous System . New York, Alan R Liss Inc, 1983, pp 473-491. 23. Abdul-Ghani AS, Bradford HF, Cox DWG, et al: Peripheral sensory stimulation and the release of transmitter amino acids in vivo from specific regions of cerebral cortex . Brain Res 1979;171:55-56.Crossref 24. Granata AR, Reis DJ: Release of [3H]Lglutamic acid (L-glu) and [3H]D-aspartic acid (D-asp) in the area of nucleus tractus solitarius in vivo produced by stimulation of the vagus nerve . Brain Res 1983;259:77-93.Crossref 25. Fonnum F, Lund-Karlsen R, Malthe-Sorensen D, et al: High affinity transport systems and their role in transmitter action , in Cotman CW, Poste G, Nicholson GL (eds): The Cell Surface and Neuronal Function . Amsterdam, Elsevier/North Holland Biomedical Press, 1980, pp 455-504. 26. Johnston GAR, Lodge D, Bernstein JC, et al: Potentiation of L-glutamate and L-aspartate excitation of cat spinal neurones by the stereo isomers of threo-3-hydroxyaspartate . J Neurochem 1980;34:241-243.Crossref 27. Henn F, Hamberger A: Glial cell function: Uptake of transmitter substances . Proc Natl Acad Sci USA 1971;68:2686-2690.Crossref 28. Young AB, Penney JB, Dauth GW, et al: Glutamate or aspartate as a possible neurotransmitter of cerebral corticofugal fibers in the monkey . Neurology 1983;33:1513-1516.Crossref 29. Fagg GE, Foster AC: Amino acid neurotransmitters and their pathways in the mammalian central nervous system . Neuroscience 1983;9:701-719.Crossref 30. Davies J, Evans RH, Francis AA, et al: Excitatory amino acid receptors and synaptic excitation in the mammalian central nervous system . J Physiol 1980;75:641-645. 31. Fagg GE, Foster AC, Mena EE, et al: Chloride and calcium ions reveal a pharmacologically distinct population of L-glutamate binding sites in synaptic membranes: Correspondence between biochemical and electrophysiological data . J Neurosci 1982;2:958-965. 32. Davies J, Evans RH, Jones AW, et al: Recent advances in the pharmacology of excitatory amino acids in the mammalian central nervous system , in Fuxe K, Roberts PJ, Schwarcz R (eds): Excitotoxins . New York, Macmillan Publishing Co Inc, 1983, pp 43-54. 33. Thomson AM, West DC, Lodge D: An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamaine? Nature 1985;313:479-481.Crossref 34. Crepel F, Dhanjal SS, Sears TA: Effect of glutamate, aspartate and related derivatives on cerebellar Purkinje cell dendrites in the rat: An in vitro study . J Physiol 1982;329:297-317. 35. Koerner JF, Cotman CW: Micromolar L-2-amino-4-phosphonobutyric acid selectively inhibits perforant path synapses from lateral entorhinal cortex . Brain Res 1981;216:192-198.Crossref 36. Harris EW, Ganong AH, Cotman CW: Long-term potentiation in the hippocampus involves activation of N-methyl-D-aspartate receptors . Brain Res 1984;323:132-137.Crossref 37. Collingridge GL, Kehl SJ, McLennan H: Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus . J Physiol 1983;334:33-46. 38. Foster AC, Fagg GE: Acidic amino acid binding sites in mammalian neuronal membranes: Their characteristics and relationship to synaptic receptors . Brain Res Rev 1984;7:103-164.Crossref 39. 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Journal

Archives of NeurologyAmerican Medical Association

Published: Oct 1, 1986

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