[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content

Advertisement

Springer Nature Link
Log in

The Recurrent Mossy Fiber Pathway of the Epileptic Brain

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The dentate gyrus is believed to play a key role in the pathogenesis of temporal lobe epilepsy. In normal brain the dentate granule cells serve as a high-resistance gate or filter, inhibiting the propagation of seizures from the entorhinal cortex to the hippocampus. The filtering function of the dentate gyrus depends in part on the near absence of monosynaptic connections among granule cells. In humans with temporal lobe epilepsy and in animal models of temporal lobe epilepsy, dentate granule cells form an interconnected synaptic network associated with loss of hilar interneurons. This recurrent mossy fiber pathway mediates reverberating excitation that can reduce the threshold for granule cell synchronization. Factors that augment activity in this pathway include modest increases in [K+]o; loss of GABA inhibition; short-term, frequency-dependent facilitation (frequencies of 1–2 Hz); feedback activation of kainate autoreceptors; and release of zinc from recurrent mossy fiber boutons. Factors that diminish activity include short-term, frequency-dependent depression (frequencies <1 Hz); feedback activation of type II metabotropic glutamate receptors; and the potential release of GABA, neuropeptide Y, adenosine, and dynorphin from recurrent mossy fiber boutons. The axon sprouting and reactive synaptogenesis that follow seizure-related brain damage can also create or strengthen recurrent excitation in other brain regions. These changes are expected to facilitate participation of these regions in seizures. Thus, reactive processes that are often considered important for recovery of function after most brain injuries probably contribute to neurological dysfunction in epilepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Cotman, C. W. and Lynch, G. S. 1976. Reactive synaptogenesis in the adult nervous system. Pages 69-108, in Barondes, S. (ed.), Neuronal Recognition, New York, Plenum.

    Google Scholar 

  2. Cotman, C. W. and Nadler, J. V. 1978. Reactive synaptogenesis in the hippocampus. Pages 227-271, in Cotman, C. W. (ed.), Neuronal Plasticity, New York, Raven.

    Google Scholar 

  3. Cotman, C. W., Nieto-Sampedro, M., and Harris, E. W. 1981. Synapse replacement in the nervous system of adult vertebrates. Physiol. Rev. 61:684-784.

    PubMed  Google Scholar 

  4. Steward, O., Cotman, C. W., and Lynch, G. S. 1974. Growth of a new fiber projection in the brain of adult rats: Reinnervation of the dentate gyrus by the contralateral entorhinal cortex following ipsilateral entorhinal lesions. Exp. Brain Res. 20:45-66.

    Google Scholar 

  5. Steward, O. 1976. Reinnervation of dentate gyrus by homologous afferents following entorhinal cortical lesions in adult rats. Science 194:426-428.

    PubMed  Google Scholar 

  6. Goldowitz, D., Scheff, S. W., and Cotman, C. W. 1979. The specificity of reactive synaptogenesis: A comparative study in the adult rat hippocampal formation. Brain Res. 170:427-441.

    PubMed  Google Scholar 

  7. Nadler, J. V., Perry, B. W., Gentry, C., and Cotman, C. W. 1980. Loss and reacquisition of hippocampal synapses after selective destruction of CA3-CA4 afferents with kainic acid. Brain Res. 191:387-403.

    PubMed  Google Scholar 

  8. Frotscher, M., Heimrich, B., and Deller, T. 1997. Sprouting in the hippocampus is layer-specific. Trends Neurosci. 20:218-223.

    PubMed  Google Scholar 

  9. Loesche, J. and Steward, O. 1977. Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: Recovery of alternation performance following unilateral entorhinal cortex lesions. Brain Res. Bull. 2:31-39.

    PubMed  Google Scholar 

  10. Scheff, S. W. and Cotman, C. W. 1977. Recovery of spontaneous alternation following lesions of the entorhinal cortex in adult rats: Possible correlation to axon sprouting. Behav. Biol. 21:286-293.

    PubMed  Google Scholar 

  11. Steward, O., Loesche, J., and Horten, W. C. 1977. Behavioral correlates of denervation and reinnervation of the hippocampal formation of the rat: Open field activity and cue utilization following bilateral entorhinal cortical lesions. Brain Res. Bull. 2:41-48.

    PubMed  Google Scholar 

  12. McCouch, G. P., Austin, G. M., Liu, C.-N., and Liu, C. Y. 1958. Sprouting as a cause of spasticity. J. Neurophysiol. 21:205-216.

    PubMed  Google Scholar 

  13. Schneider, G. E. 1973. Early lesions of superior colliculus: Factors affecting the formation of abnormal retinal projections. Brain Behav. Evol. 8:73-109.

    PubMed  Google Scholar 

  14. Nadler, J. V., Perry, B. W., and Cotman, C. W. 1978. Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature 271:676-677.

    PubMed  Google Scholar 

  15. Nadler, J. V. 1981. Kainic acid as a tool for the study of temporal lobe epilepsy. Life Sci. 29:2031-2042.

    PubMed  Google Scholar 

  16. Cavalheiro, E. A., Riche, D. A., and Le Gal La Salle, G. 1982. Long-term effects of intrahippocampal kainic acid injection in rats: A method for inducing spontaneous recurrent seizures. Electroenceph. Clin. Neurophysiol. 53:581-589.

    PubMed  Google Scholar 

  17. Cronin, J. and Dudek, F. E. 1988. Chronic seizures and collateral sprouting of dentate mossy fibers after kainic acid treatment in rats. Brain Res. 474:181-184.

    PubMed  Google Scholar 

  18. Nadler, J. V., Perry, B. W., and Cotman, C. W. 1980. Selective reinnervation of hippocampal area CA1 and the fascia dentata after destruction of CA3-CA4 afferents with kainic acid. Brain Res. 182:1-9.

    PubMed  Google Scholar 

  19. Okazaki, M. M., Evenson, D. A., and Nadler, J. V. 1995. Hippocampal mossy fiber sprouting and synapse formation after status epilepticus in rats: Visualization after retrograde transport of biocytin. J. Comp. Neurol. 352:515-534.

    PubMed  Google Scholar 

  20. Buckmaster, P. S., Zhang, G. F., and Yamawaki, R. 2002. Axon sprouting in a model of temporal lobe epilepsy creates a predominantly excitatory feedback circuit. J. Neurosci. 22:6650-6658.

    PubMed  Google Scholar 

  21. Perez, Y., Morin, F., Beaulieu, C., and Lacaille, J. C. 1996. Axonal sprouting of CA1 pyramidal cells in hyperexcitable hippocampal slices of kainate-treated rats. Eur. J. Neurosci. 8:736-748.

    PubMed  Google Scholar 

  22. Esclapez, M., Hirsch, J. C., Ben-Ari, Y., and Bernard, C. 1999. Newly formed excitatory pathways provide a substrate for hyperexcitability in experimental temporal lobe epilepsy. J. Comp. Neurol. 408:449-460.

    PubMed  Google Scholar 

  23. Prince, D. A., Salin, P., Tseng, G. F., Hoffman, S., and Parada, I. 1997. Axonal sprouting and epileptogenesis. Adv. Neurol. 72: 1-8.

    PubMed  Google Scholar 

  24. Represa, A., Robain, O., Tremblay, E., and Ben-Ari, Y. 1989. Hippocampal plasticity in childhood epilepsy. Neurosci. Lett. 99:351-355.

    PubMed  Google Scholar 

  25. Sutula, T., Cascino, G., Cavazos, J., Parada, I., and Ramirez, L. 1989. Mossy fiber synaptic reorganization in the epileptic human temporal lobe. Ann. Neurol. 26:321-330.

    PubMed  Google Scholar 

  26. Babb, T. L., Kupfer, W. R., Pretorius, J. K., Crandall, P. H., and Levesque, M. F. 1991. Synaptic reorganization by mossy fibers in human epileptic fascia dentata. Neuroscience 42:351-363.

    PubMed  Google Scholar 

  27. Franck, J. E., Pokorny, J., Kunkel, D. D., and Schwartzkroin, P. A. 1995. Physiologic and morphologic characteristics of granule cell circuitry in human epileptic hippocampus. Epilepsia 36:543-558.

    PubMed  Google Scholar 

  28. Kaneko, S., Okada, M., Iwasa, H., Yamakawa, K., and Hirose, S. 2002. Genetics of epilepsy: Current status and perspectives. Neurosci. Res. 44:11-30.

    PubMed  Google Scholar 

  29. Turski, W. A., Cavalheiro, E. A., Schwarz, M., Czuczwar, S. J., Kleinrok, Z., and Turski, L. 1983. Limbic seizures produced by pilocarpine in rats: Behavioural, electroencephalographic and neuropathological study. Behav. Brain Res. 9:315-335.

    PubMed  Google Scholar 

  30. Lothman, E. W., Bertram, E. H., Bekenstein, J. W., and Perlin, J. B. 1989. Self-sustaining limbic status epilepticus induced by 'continuous' hippocampal stimulation: Electrographic and behavioral characteristics. Epilepsy Res. 3:107-119.

    PubMed  Google Scholar 

  31. Lothman, E. W., Bertram, E. H., Kapur, J., and Stringer, J. L. 1990. Recurrent spontaneous hippocampal seizures in the rat as a chronic sequela to limbic status epilepticus. Epilepsy Res. 6:110-118.

    PubMed  Google Scholar 

  32. Okazaki, M. M., Molnár, P., and Nadler, J. V. 1999. Recurrent mossy fiber pathway in rat dentate gyrus: Synaptic currents evoked in presence and absence of seizure-induced growth. J. Neurophysiol. 81:1645-1660.

    PubMed  Google Scholar 

  33. Buckmaster, P. S. and Dudek, F. E. 1997. Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. J. Comp. Neurol. 385:385-404.

    PubMed  Google Scholar 

  34. Buckmaster, P. S. and Jongen-Rêlo, A. L. 1999. Highly specific neuron loss preserves lateral inhibitory circuits in the dentate gyrus of kainate-induced epileptic rats. J. Neurosci. 19: 9519-9529.

    PubMed  Google Scholar 

  35. Margerison, J. H. and Corsellis, J. A. N. 1966. Epilepsy and the temporal lobes. Brain 89:499-530.

    PubMed  Google Scholar 

  36. Sloviter, R. S. 1987. Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science 235:73-76.

    PubMed  Google Scholar 

  37. Zimmer, J. 1974. Proximity as a factor in the regulation of aberrant axonal growth in the postnatally deafferented fascia dentata. Brain Res. 72:137-142.

    PubMed  Google Scholar 

  38. Parent, J. M., Yu, T. W., Leibowitz, R. T., Geschwind, D. H., Sloviter, R. S., and Lowenstein, D. H. 1997. Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J. Neurosci. 17:3727-3738.

    PubMed  Google Scholar 

  39. Scharfman, H. E., Goodman, J. H., and Sollas, A. L. 2000. Granule-like neurons at the hilar/CA3 border after status epilepticus and their synchrony with area CA3 pyramidal cells: Functional implications of seizure-induced neurogenesis. J. Neurosci. 20:6144-6158.

    PubMed  Google Scholar 

  40. Dashtipour, K., Tran, P. H., Okazaki, M. M., Nadler, J. V., and Ribak, C. E. 2001. Ultrastructural features and synaptic connections of hilar ectopic granule cells in the rat dentate gyrus are different from those of granule cells in the granule cell layer. Brain Res. 890:261-271.

    PubMed  Google Scholar 

  41. Spigelman, I., Yan, X.-X., Obenaus, A., Lee, E. Y.-S., Wasterlain C. G., and Ribak, C. E. 1998. Dentate granule cells form novel basal dendrites in a rat model of temporal lobe epilepsy. Neuroscience 86:109-120.

    PubMed  Google Scholar 

  42. Buckmaster, P. S. and Dudek, F. E. 1999. In vivo intracellular analysis of granule cell axon reorganization in epileptic rats. J. Neurophysiol. 81:712-721.

    PubMed  Google Scholar 

  43. Ribak, C. E., Tran, P. H., Spigelman, I., Okazaki, M. M., and Nadler, J. V. 2000. Status epilepticus-induced hilar basal dendrites on rodent granule cells contribute to recurrent excitatory circuitry. J. Comp. Neurol. 428:240-253.

    PubMed  Google Scholar 

  44. Dashtipour, K., Yan, X.-X., Dinh, T. T., Okazaki, M. M., Nadler, J. V., and Ribak, C. E. 2002. Quantitative and morphological analysis of dentate granule cells with recurrent basal dendrites from normal and epileptic rats. Hippocampus 12:235-244.

    PubMed  Google Scholar 

  45. Wuarin, J.-P. and Dudek, F. E. 2001. Excitatory synaptic input to granule cells increases with time after kainate treatment. J. Neurophysiol. 85:1067-1077.

    PubMed  Google Scholar 

  46. Buckmaster, P. S. and Dudek, F. E. 1997. Network properties of the dentate gyrus in epileptic rats with hilar neuron loss and granule cell axon reorganization. J. Neurophysiol. 77:2685-2696.

    PubMed  Google Scholar 

  47. Tauck, D. L. and Nadler, J. V. 1985. Evidence of functional mossy fiber sprouting in the hippocampal formation of kainic acid-treated rats. J. Neurosci. 5:1016-1022.

    PubMed  Google Scholar 

  48. Cronin, J., Obenaus, A., Houser, C. R., and Dudek, F. E. 1992. Electrophysiology of dentate granule cells after kainate-induced synaptic reorganization of the mossy fibers. Brain Res. 573:305-310.

    PubMed  Google Scholar 

  49. Patrylo, P. R. and Dudek, F. E. 1998. Physiological unmasking of new glutamatergic pathways in the dentate gyrus of hippocampal slices from kainate-induced epileptic rats. J. Neurophysiol. 79:418-429.

    PubMed  Google Scholar 

  50. Hardison, J. L., Okazaki, M. M., and Nadler, J. V. 2000. Modest increase in extracellular potassium unmasks effect of recurrent mossy fiber growth. J. Neurophysiol. 84:2380-2389.

    PubMed  Google Scholar 

  51. Krnjević, K., Morris, M. E., and Reiffenstein, R. J. 1982. Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat's hippocampus. Can. J. Physiol. Pharmacol. 60:1643-1657.

    PubMed  Google Scholar 

  52. Walz, W. and Herz, L. 1983. Functional interactions between neurons and astrocytes: II. Potassium homeostasis at the cellular level. Prog. Neurobiol. 20:133-183.

    PubMed  Google Scholar 

  53. Obenaus, A., Esclapez, M., and Houser, C. R. 1993. Loss of glutamate decarboylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures. J. Neurosci. 13: 4470-4485.

    PubMed  Google Scholar 

  54. Haas, K. Z., Sperber, E. F., Moshé, S. L., and Stanton, P. K. 1996. Kainic acid-induced seizures enhance dentate gyrus inhibition by downregulation of GABAB receptors. J. Neurosci. 16: 4250-4260.

    PubMed  Google Scholar 

  55. Wilson, C. L., Khan, S. U., Engel, J., Isokawa, M., Babb, T. L., and Behnke, E. J. 1998. Paired pulse suppression and facilitation in human epileptogenic hippocampal formation. Epilepsy Res. 31:211-230.

    PubMed  Google Scholar 

  56. Wittner, L., Maglóczky, A., Borhegyi, Z., Halász, P., Tóth, S., Erőss, L., Szabó, Z., and Freund, T. F. 2001. Preservation of peri-somatic inhibitory input of granule cells in the epileptic human dentate gyrus. Neuroscience 108:587-600.

    PubMed  Google Scholar 

  57. Molnár, P. and Nadler, J. V. 1999. Mossy fiber-granule cell synapses in the normal and epileptic rat dentate gyrus studied with minimal laser photostimulation. J. Neurophysiol. 82:1883-1894.

    PubMed  Google Scholar 

  58. Feng, L., Molnár, P., and Nadler, J. V. 2003. Short-term frequency-dendent plasticity at recurrent mossy fiber synapses of the epileptic brain. J. Neurosci. 23:5381-5390.

    PubMed  Google Scholar 

  59. Traub, R. D. and Dingledine, R. 1990. Model of synchronized epileptiform bursts induced by high potassium in CA3 region of rat hippocampal slice: Role of spontaneous EPSPs in initiation. J. Neurophysiol. 64:1009-1018.

    PubMed  Google Scholar 

  60. Jung, M. W. and McNaughton, B. L. 1993. Spatial selectivity of unit activity in the hippocampal granular layer. Hippocampus 3:165-182.

    Google Scholar 

  61. Henze, D. A., Wittner, L., and Buzsáki, G. 2002. Single granule cells reliably discharge targets in the hippocampal CA3 network in vivo. Nat. Neurosci. 5:790-795.

    PubMed  Google Scholar 

  62. Bragin, A., Engel, J., Wilson, C. L., Fried, I., and Mathern, G. W. 1999. Hippocampal and entorhinal cortex high-frequency oscillations (100–500 Hz) in human epileptic brain and in kainic acid-treated rats with chronic seizures. Epilepsia 40:127-137.

    PubMed  Google Scholar 

  63. Finnerty, G. T. and Jefferys, J. G. 2000. 9–16 Hz oscillation precedes secondary generalization of seizures in the rat tetanus toxin model of epilepsy. J. Neurophysiol. 83:2217-2226.

    PubMed  Google Scholar 

  64. Schmitz, D., Mellor, J., and Nicoll, R. A. 2001. Presynaptic kainate receptor mediation of frequency facilitation at hippocampal mossy fiber synapses. Science 291:1972-1976.

    PubMed  Google Scholar 

  65. Petralia, R. S., Wang, Y. X., and Wenthold, R. J. 1994. Histological and ultrastructural localization of the kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies. J. Comp. Neurol. 349:85-110.

    PubMed  Google Scholar 

  66. Kamiya, H., Ozawa, S., and Manabe, T. 2002. Kainate receptor-dependent short-term plasticity of presynaptic Ca2+ influx at the hippocampal mossy fiber synapses. J. Neurosci. 22: 9237-9243.

    PubMed  Google Scholar 

  67. Shigemoto, R., Kinoshita, A., Wada, E., Nomura, S., Ohishi, H., Takada, M., Flor, P. J., Neki, A., Abe, T., Nakanishi, S., and Mizuno, N. 1997. Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J. Neurosci. 17:7503-7522.

    PubMed  Google Scholar 

  68. Frederickson, C. J. and Danscher, G. 1990. Zinc containing neurons in hippocampus and related CNS structures. Prog. Brain Res. 83:71-84.

    PubMed  Google Scholar 

  69. Vogt, K., Mellor, J., Tong, G., and Nicoll, R. 2000. The actions of synaptically released zinc at hippocampal mossy fiber synapses. Neuron 26:187-196.

    PubMed  Google Scholar 

  70. Molnár, P. and Nadler, J. V. 2001. Synaptically-released zinc inhibits N-methyl-D-aspartate receptor activation at recurrent mossy fiber synapses. Brain Res. 910:205-207.

    PubMed  Google Scholar 

  71. Timofeeva, O. A. and Nadler, J. V. 2002. Regulation of NMDA receptor-mediated granule cell epileptiform activity by zinc and type II metabotropic glutamate receptors. Soc. Neurosci. Abstr. 603.9.

  72. Gibbs, J. W., Shumate, M. D., and Coulter, D. A. 1997. Differential epilepsy-associated alterations in postsynaptic GABAA receptor function in dentate granule and CA1 neurons. J. Neurophysiol. 77:1924-1938.

    PubMed  Google Scholar 

  73. Shumate, M. D., Lin, D. D., Gibbs, J. W., Holloway, K. L., and Coulter, D. A. 1998. GABAA receptor function in epileptic human dentate granule cells: Comparison to epileptic and control rat. Epilepsy Res. 32:114-128.

    PubMed  Google Scholar 

  74. Buhl, E. H., Otis, T. S., and Mody, I. 1996. Zinc-induced collapse of augmented inhibition by GABA in a temporal lobe epilepsy model. Science 271:369-373.

    PubMed  Google Scholar 

  75. Molnár, P. and Nadler, J. V. 2001. Lack of effect of mossy fiber-released zinc on granule cell GABAA receptors in the pilocarpine model of epilepsy. J. Neurophysiol. 85:1932-1940.

    PubMed  Google Scholar 

  76. Li, Y., Hough, C. J., Frederickson, C. J., and Sarvey, J. M. 2001. Induction of mossy fiber→CA3 long-term potentiation requires translocation of synaptically released Zn2+. J. Neurosci. 21:8015-8025.

    PubMed  Google Scholar 

  77. Li, Y., Hough, C. J., Suh, S. W., Sarvey, J. M., and Frederickson, C. J. 2001. Rapid translocation of Zn2+ from presynaptic terminals into postsynaptic hippocampal neurons after physiological stimulation. J. Neurophysiol. 86:2597-2604.

    PubMed  Google Scholar 

  78. Spiridon, M., Kamm, D., Billups, B., Mobbs, P., and Attwell, D. 1998. Modulation by zinc of the glutamate transporters in glial cells and cones isolated from the tiger salamander retina. J. Physiol. 506:363-376.

    PubMed  Google Scholar 

  79. Vandenberg, R. J., Mitrovic, A. D., and Johnston, G. A. R. 1998. Molecular basis for differential inhibition of glutamate transporter subtypes by zinc ions. Mol. Pharmacol. 54:189-196.

    PubMed  Google Scholar 

  80. Dreixler, J. C. and Leonard, J. P. 1994. Subunit-specific enhancement of glutamate receptor responses by zinc. Mol. Brain Res. 22:144-150.

    PubMed  Google Scholar 

  81. Lin, D. D., Cohen, A. S., and Coulter, D. A. 2001. Zinc-induced augmentation of excitatory synaptic currents and glutamate receptor responses in hippocampal CA3 neurons. J. Neurophysiol. 85:1185-1196.

    PubMed  Google Scholar 

  82. Yamamoto, C., Sawada, S., and Ohno-Shosaku, T. 1993. Quantal analysis of modulating action of adenosine on the mossy fiber synapse in hippocampal slices. Hippocampus 3:87-92.

    PubMed  Google Scholar 

  83. Castillo, P. E., Salin, P. A., Weisskopf, M. G., and Nicoll, R. A. 1996. Characterizing the site and mode of action of dynorphin at hippocampal mossy fiber synapses in the guinea pig. J. Neurosci. 16:5942-5950.

    PubMed  Google Scholar 

  84. Terman, G. W., Drake, C. T., Simmons, M. L., Milner, T. A., and Chavkin, C. 2000. Opioid modulation of recurrent excitation in the hippocampal dentate gyrus. J. Neurosci. 20:4379-4388.

    PubMed  Google Scholar 

  85. Walker, M. C., Ruiz, A., and Kullmann, D. M. 2001. Monosynaptic GABAergic signaling from dentate to CA3 with a pharmacological and physiological profile typical of mossy fiber synapses. Neuron 29:703-715.

    PubMed  Google Scholar 

  86. Gutiérrez, R. 2002. Activity-dependent expression of simultaneous glutamatergic and GABAergic neurotransmission from the mossy fibers in vitro. J. Neurophysiol. 87:2562-2570.

    PubMed  Google Scholar 

  87. Collins, R. C., Tearse, R. G., and Lothman, E. W. 1983. Functional anatomy of limbic seizures: Focal discharges from medial entorhinal cortex in rat. Brain Res. 280:25-40.

    PubMed  Google Scholar 

  88. Stringer, J. L., Williamson, J. M., and Lothman, E. W. 1989. Induction of paroxysmal discharges in the dentate gyrus: Frequency dependence and relationship to afterdischarge production. J. Neurophysiol. 62:126-135.

    PubMed  Google Scholar 

  89. Lothman, E. W., Stringer, J. L., and Bertram, E. H. 1992. The dentate gyrus as a control point for seizures in the hippocampus and beyond. Epilepsy Res. Suppl. 7:301-313.

    PubMed  Google Scholar 

  90. Miles, R., Wong, R. K. S., and Traub, R. D. 1984. Synchronized afterdischarges in the hippocampus: Contribution of local circuit interaction. Neuroscience 12:1016-1022.

    Google Scholar 

  91. Gorter, J. A., van Vliet, E. A., Aronica, E., and Lopes da Silva, F. H. 2001. Progression of spontaneous seizures after status epilepticus is associated with mossy fiber sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin-immunoreactive neurons. Eur. J. Neurosci. 13:657-669.

    PubMed  Google Scholar 

  92. Zhang, X., Cui, S.-S., Wallace, A. E., Hannesson, D. K., Schmued, L. C., Saucier, D. M., Honer, W. G., and Corcoran, M. E. 2002. Relations between brain pathology and temporal lobe epilepsy. J. Neurosci. 22:6052-6061.

    PubMed  Google Scholar 

  93. Longo, B. M. and Mello, L. E. A. M. 1997. Blockade of pilocarpine-or kainate-induced mossy fiber sprouting by cycloheximide does not prevent subsequent epileptogenesis in rats. Neurosci. Lett. 226:163-166.

    PubMed  Google Scholar 

  94. Longo, B. M. and Mello, L. E. A. M. 1998. Supragranular mossy fiber sprouting is not necessary for spontaneous seizures in the intrahippocampal kainate model of epilepsy in the rat. Epilepsy Res. 32:172-182.

    PubMed  Google Scholar 

  95. Williams, P. A., Wuarin, J.-P., Dou, P., Ferraro, D. J., and Dudek, F. E. 2002. Reassessment of the effects of cycloheximide on mossy fiber sprouting and epileptogenesis in the pilocarpine model of temporal lobe epilepsy. J. Neurophysiol. 88:2075-2087.

    PubMed  Google Scholar 

  96. Du, F., Whetsell, W. O., Abou-Khalil, B., Blumenkopf, B., Lothman, E. W., and Schwarcz, R. 1993. Preferential neuronal loss in layer III of the entorhinal cortex in patients with temporal lobe epilepsy. Epilepsy Res. 16:223-233.

    PubMed  Google Scholar 

  97. Du, F., Eid, T., Lothman, E. W., Köhler, C., and Schwarcz, R. 1995. Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. J. Neurosci. 15:6301-6313.

    PubMed  Google Scholar 

  98. Scharfman, H. E., Goodman, J. H., Du, F., and Schwarcz, R. 1998. Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)-induced entorhinal cortical neuron loss. J. Neurophysiol. 80:3031-3046.

    PubMed  Google Scholar 

  99. Schweitzer, J. S., Patrylo, P. R., and Dudek, F. E. 1992. Prolonged field bursts in the dentate gyrus: Dependence on low calcium, high potassium and nonsynaptic mechanisms. J. Neurophysiol. 68:2016-2025.

    PubMed  Google Scholar 

  100. Schweitzer, J. S. and Williamson, A. 1995. Relationship between synaptic activity and prolonged field bursts in the dentate gyrus of the rat hippocampal slice. J. Neurophysiol. 74:1947-1952.

    PubMed  Google Scholar 

  101. Pan, E. and Stringer, J. L. 1996. Burst characteristics of dentate gyrus granule cells: Evidence for endogenous and non-synaptic properties. J. Neurophysiol. 75:124-132.

    PubMed  Google Scholar 

  102. Acsady, L., Kamondi, A., Sik, A., Freund, T., and Buzsáki, G. 1998. GABAergic cells are the major postsynaptic targets of mossy fibers in the rat hippocampus. J. Neurosci. 18:3386-3403.

    PubMed  Google Scholar 

  103. Toth, K., Suares, G., Lawrence, J. J., Philips-Tansey, E., and McBain, C. J. 2000. Differential mechanisms of transmission at three types of mossy fiber synapse. J. Neurosci. 20:8279-8289.

    PubMed  Google Scholar 

  104. Sloviter, R. S. 1991. Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: The “dormant basket cell” hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus 1:41-66.

    PubMed  Google Scholar 

  105. Rice, A., Rafiq, A., Shapiro, S. M., Jakoi, E. R., Coulter, D. A., and DeLorenzo, R. J. 1996. Long-lasting reduction of inhibitory function and gamma-aminobutyric acid type A receptor subunit mRNA expression in a model of temporal lobe epilepsy. Proc. Natl. Acad. Sci. USA 93:9665-9669.

    PubMed  Google Scholar 

  106. Williamson, A., Patrylo, P. R., and Spencer, D. D. 1999. Decrease in inhibition in dentate granule cells from patients with medial temporal lobe epilepsy. Ann. Neurol. 45:92-99.

    PubMed  Google Scholar 

  107. Doherty, J. and Dingledine, R. 2002. Reduced excitatory drive onto interneurons in the dentate gyrus after status epilepticus. J. Neurosci. 21:2048-2057.

    Google Scholar 

  108. Isokawa, M. 1996. Decrement of GABAA receptor-mediated inhibitory postsynaptic currents in dentate granule cells in epileptic hippocampus. J. Neurophysiol. 75:1901-1908.

    PubMed  Google Scholar 

  109. Lynch, M., Sayin, ü., Golarai, G., and Sutula, T. 2000. NMDA receptor-dependent plasticity of granule cell spiking in the dentate gyrus of normal and epileptic rats. J. Neurophysiol. 84:2868-2879.

    PubMed  Google Scholar 

  110. Mody, I., Reynolds, J. N., Salter, M. W., Carlen, P. L., and MacDonald, J. F. 1990. Kindling-induced epilepsy alters calcium currents in granule cells of rat hippocampal slices. Brain Res. 531:88-94.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Cancer Biology and Department of Neurobiology, Duke University Medical Center, Box 3813, Durham, North Carolina, 27710

    J. Victor Nadler

Authors
  1. J. Victor Nadler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nadler, J.V. The Recurrent Mossy Fiber Pathway of the Epileptic Brain. Neurochem Res 28, 1649–1658 (2003). https://doi.org/10.1023/A:1026004904199

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026004904199

Search

Navigation