Advertisement

Control of Epileptic Seizures

Another function for the basal ganglia?
  • Colin Deransart
  • Véronique Riban
  • Laurent Vercueil
  • Karine Nail-Boucherie
  • Christian Marescaux
  • Antoine Depaulis
Part of the Advances in Behavioral Biology book series (ABBI, volume 54)

Abstract

During the last two decades, evidence has accumulated to demonstrate the existence, in the central nervous system, of an endogenous mechanism that exerts an inhibitory control over different forms of epileptic seizures. The substantia nigra and the superior colliculus have been described as key structures in this control circuit: inhibition of GABAergic neurons of the substantia nigra pars reticulata results in suppression of seizures in various animal models of epilepsy. The role in this control mechanism of the direct GABAergic projection from the striatum to the substantia nigra and of the indirect pathway from the striatum through the globus pallidus and the subthalamic nucleus, was examined in a genetic model of absence seizures in the rat. In this model, pharmacological manipulations of both the direct and indirect pathways resulted in modulation of absence seizures. Activation of the direct pathway or inhibition of the indirect pathway suppressed absence seizures through disinhibition of neurons in the deep and intermediate layers of the superior colliculus. Dopamine D l and D2 receptors in the nucleus accumbens, appear to be critical in these suppressive effects. Along with data from the literature, our results suggest that basal ganglia circuits play a major role in the modulation of seizures and provide a framework to understand the role of these circuits in the modulation of generalized seizures.

Keywords

Basal Ganglion Substantia Nigra Nucleus Accumbens Epileptic Seizure Superior Colliculus 
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. Afifi, A., Basal ganglia: functional anatomy and physiology. Part 2. J. Child Neurology, 9 (1994) 352–361.CrossRefGoogle Scholar
  2. Akkal, D., Burbaud, P., Audin, J. and Bioulac. B., Responses of substantia nigra pars reticulata neurons to intrastriatal D1 and D2 dopaminergic agonist injections in the rat, Neurosci Lett, 213 (1996) 66–70.PubMedCrossRefGoogle Scholar
  3. Al-Tajir, G. and Starr, M.S., Anticonvulsant effect of striatal dopamine D2 receptor stimulation: Depen-dence on cortical circuits?, Neuroscience. 43 (1991a) 51–57.PubMedCrossRefGoogle Scholar
  4. Al-Tajir, G. and Starr, M.S., D-2 agonists protect rodents against pilocarpine-induced convulsions by stimulating D-2 receptors in the striatum. but not in the substantia nigra, Pharm. Biochem. Behan, 39 (1991b) 109–113.Google Scholar
  5. Alexander, G and Crutcher, M., Functional architecture of basal ganglia circuits neural substrates of parallel processing, Trends Neurosci., 13 (1990) 266–271.PubMedCrossRefGoogle Scholar
  6. Benazzouz, A., Piallat, B., Pollak, P. and Benabid, A.L., Responses of substantia nigra pars reticulata and globus pallidus complex to high frequency stimulation of the subthalamic nucleus in rats: Electro-physiological data, Neurosci Lett, 189 (1995) 77–80.PubMedCrossRefGoogle Scholar
  7. Bonhaus, D., Russell, R. and McNamara, J. Activation of substantia nigra pars reticulata neurons: role in the initiation and behavioral expression of kindled seizures. Brain Res 545 (1991) 41–48.PubMedCrossRefGoogle Scholar
  8. Browning, R., Neuroanatomical localization of structures responsible for seizures in the GEPR: lesion studies. Life Sci 39 (1986) 857–867.PubMedCrossRefGoogle Scholar
  9. Cavalheiro, E. and Turski, L., Intrastriatal N-methyl-D-aspartate prevents amygdala kindled seizures in rats, Brain Res, 377 (1986) 173–176.PubMedCrossRefGoogle Scholar
  10. Chevalier, G and Deniau, J., Disinhibition as a basic procss in the expression of striatal functions, Trends Neurosci, 13 (1990) 277–280.PubMedCrossRefGoogle Scholar
  11. Chevalier, G, Vacher, S., Deniau, J. and Desban, M., Disinhibition as a basic process in the expression of striatal functions. I. The striato-nigral influence on tecto-spinal/tecto-diencephalic neurons, Brain Res, 334 (1985) 215–226.PubMedCrossRefGoogle Scholar
  12. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia, 22 (1981) 489–501.CrossRefGoogle Scholar
  13. Csernansky, J., Melletin, J., Beauclair, L. and Lombrozo, L., Mesolimbic dopaminergic supersensivity following electrical kindling of the amygdala, Biol. Psychiatry, 23 (1988) 285–294.Google Scholar
  14. Danober, L., Deransart, C., Depaulis, A., Vergnes, M. and Marescaux, C., Pathophysiological mechanisms of genetic absence epilepsy in the rat, Prog. Neurobiol., 54 (1998) 1–31.Google Scholar
  15. Delong, M., Primate models of movement disorders of basal ganglia origin, Trends Neurosci., 13 (1990). 281–285.PubMedCrossRefGoogle Scholar
  16. Deniau, JM and Thierry, AM., Anatomical segregation of information processing in the rat substantia nigra pars reticulata. In: The basal ganglia and new surgical approaches for Parkinson’s diseases, Advances in Neurology 74 (1997) 83–96, Obeso JA, DeLong MR, Ohye C, Marsden CD (eds), Lippincott-Raven Publishers, Philadelphia.Google Scholar
  17. Depaulis, A., Liu, Z., Vergnes, M., Marescaux, C., Micheletti, G. and Warier, J., Suppression of spontaneous generalized non-convulsive seizures in the rat by microinjection of GABA antagonists into the superior colliculus, Epilepsy Res, 5 (1990a) 192–198.PubMedCrossRefGoogle Scholar
  18. Depaulis, A., Marescaux, C., Liu, Z. and Vergnes, M., The GABAergic nigro-collicular pathway is not involved in the inhibitory control of audiogenic seizures in the rat. Neurosci Letters 111 (1990b) 269–274.Google Scholar
  19. Depaulis, A., Snead, O.I., Marescaux, C. and Vergnes, M., Suppressive effects of intranigral injection of muscimol in three models of generalized non-convulsive epilepsy induced by chemical agents, Brain Res., 498 (1989) 64–72.PubMedCrossRefGoogle Scholar
  20. Depaulis, A., Vergnes, M., Liu, Z., Kempf, E. and Marescaux, C. Involvement of the nigral output pathways in the inhibitory control of the substantia nigra over generakized non-convulsive seizures in the rat, Neuroscience 39 (1990c) 339–349.PubMedCrossRefGoogle Scholar
  21. Depaulis, A., Vergnes, M. and Marescaux, C., Endogenous control of epilepsy: the nigral inhibitory system, Prog Neurobiol, 42 (1994) 33–52.PubMedCrossRefGoogle Scholar
  22. Depaulis, A., Vergnes, M., Marescaux, C., Lannes, B. and Warter, J., Evidence that activation of GABA receptors in the substantia nigra suppresses spontaneous spike-and-wave discharges in the rat, Brain Res, 448 (1988) 20–29.PubMedCrossRefGoogle Scholar
  23. Deransart, C., Marescaux, C. and Depaulis, A., Involvement of nigral glutamatergic inputs in the control of seizures in a genetic model of absence epilepsy in the rat, Neurosci, 71 (1996) 721–728.CrossRefGoogle Scholar
  24. Deransart C., Lê-Pham, B.T., Hirsch L., Marescaux C. and Depaulis A., Inhibition of the substantia nigra suppresses absences and clonic seizures in audiogenic rats, but not tonic seizures: evidence for seizure specificity of the nigral control. Neuroscience 105, (2001) 203–211.PubMedCrossRefGoogle Scholar
  25. Deransart C., U B.T., Marescaux C. and Depaulis A., Role of the subthalamo-nigral input in the control of amygdala-kindled seizures in the rat. Brain Res. 807 (1998) 78–83.PubMedCrossRefGoogle Scholar
  26. Deransart C., Riban V., Lê B.T., Hechler V., Marescaux C. and Depaulis A., Evidence for the involvement of the pallidum in the modulation of seizures in a genetic model of absence epilepsy in the rat.Neurosci Letters, 265 (1999) 131–134).CrossRefGoogle Scholar
  27. Deransart C., Riban V., Ik B.T., Marescaux C. and Depaulis A., Dopamine in the striatum modulates seizures in a genetic model of absence epilepsy in the rat. Neurosci. 100, (2000) 335–344.CrossRefGoogle Scholar
  28. Dragunow, M., Endogenous anticonvulsant substances. Neurosci Biobehav Rev 10 (1986) 229–244.PubMedCrossRefGoogle Scholar
  29. Drinkenburg, W.H., Coenen, A.M., Vossen, J.M. and Vanluijtelaar, E.L., Sleep deprivation and spike-wave discharges in epileptic rats, Sleep, 18 (1995) 252–256.PubMedGoogle Scholar
  30. Engel, J.Jr., Inhibitory mechanisms of epileptic seizure generation, In: Fahn, S., Hallett, M., Luders, H.O. and Marsden, C.D., ed, Negative motor phenomena, Advances in neurology, Vol 67 (1995) 157–171.Google Scholar
  31. Feger, J. and Robledo, P., The effects of activation or inhibition of the subthalamic nucleus on the metabolic and electrophysiological activities within the pallidal complex and the substantia nigra in the rat., Eur J Neurosci, 3 (1992) 947–95 2.Google Scholar
  32. Fiorino, D.F., Coury, A. and Phillips, A.G., Dynamic changes in nucleus accumbens dopamine efflux during the Coolidge effect in male rats. J Neurosci. 17 (1997) 4849–4855.PubMedGoogle Scholar
  33. Fischer, R.S., Animal models of the epilepsies. Brain Res. Rev. 14 (1989) 245–278.Google Scholar
  34. Gale, K., Mechanisms of seizure control mediated by gamma amino butyric acid: role of the substantia nigra, Fed Proc, 44 (1985) 2414–2424.PubMedGoogle Scholar
  35. Gale, K., Pazos, A., Maggio, R., Japikse, K. and Pritchard. P. Blockade of GABA receptors in superior colliculus protects against focally evoked limbic motor seizures, Brain Res, 603 (1993) 279–283.PubMedCrossRefGoogle Scholar
  36. Garant, D.S. and Gale, K., Substantia nigra-mediated anticonvulsivant actions: role of nigral output path-ways, Exp Neurol, 97 (1987) 143–159.PubMedCrossRefGoogle Scholar
  37. Groenewegen, H. and Berendse, H., Anatomical relationships between the prefrontal cortex and the basal ganglia in the rat, In: Thierry AM, Glowinski J., Goldman Rakic PS, Christen Y (eds): Motor and cognitive functions of the prefrontal cortex., Berlin: Springer-Verlag, 1994: 51–77.CrossRefGoogle Scholar
  38. Guey, J., Bureau, M., Dravet, C. and Roger, J., A study of the rhythm of petit mal absences in children in relation to prevailing situations. The use of EEG telemetry during psychological examinations, school exercises and periods of inactivity, Epilepsia, 10 (1969) 441–451.PubMedCrossRefGoogle Scholar
  39. Holmes, G.L., Classification of seizures and the epilepsies. In: Schachter S.C. and Schomer D.L., ed, The comprehensive evaluation and treatment of epilepsy. Academic Press, Inc., New York:, 1997, pp. 136.Google Scholar
  40. Jobe, P., Mishra, P., Ludvig, N. and Dailey, J., Scope and contribution of genetic models to understanding of the epilepsies. Critical Rev. Neurobiol. 6 (1991) 183–220.Google Scholar
  41. Joel, D. and Weiner, I., The organization of the basal ganglia-thalamocortical circuits: open interconnected rather than closed segregated, Neuroscience. 68 (1994) 363–379.CrossRefGoogle Scholar
  42. Jung, R., Blocking of petit-mal attacks by sensory arousal and inhibition of attacks by an active change in attention during the epileptic aura, Epilepsia, 3 (1962) 435–437.CrossRefGoogle Scholar
  43. Koob, G and Bloom, F., Cellular and molecular mechanisms of drug dependence, Science, 242 (1988) 715–723.CrossRefGoogle Scholar
  44. Lannes, B., Micheletti, G, Vergnes, M., Marescaux, C., Depaulis. A. and Warter, J., Relationship between spike-wave discharges and vigilance levels in rats with spontaneous petit mal-like epilepsy, Neurosci Lett, 94 (1988) 187–191.PubMedCrossRefGoogle Scholar
  45. Le Moal, M. and Simon, H., Mesocorticolimbic dopaminergic network: functional and regulatory roles, Physiol. Rev., 71 (1991) 155–234.PubMedGoogle Scholar
  46. Loscher, W. and Ebert, U., The role of the piriform cortex in kindling. Progress Neurobiol 50 (1996) 427–481.CrossRefGoogle Scholar
  47. Loscher, W. and Schmidt, D., Which animal model should be used in the search for new antiepileptic drugs? proposal based on experimental and clinical considerations, pilepsy Res, 2 (1988) 145–181.Google Scholar
  48. Marescaux, C., Vergnes, M. and Depaulis, A., Genetic absence epilepsy in rats from strasbourg - A review, J Neural Transm, Suppl 35 (1992) 37–70.Google Scholar
  49. Maurice, N., Deniau, J.M., Menetrey, A., Glowinski, J. and Thierry, A.M., Position of the ventral pallidum in the rat prefrontal cortex basal ganglia circuit, Neuroscience, 80 (1997) 523–534.PubMedCrossRefGoogle Scholar
  50. Meldrum, B.S., Neurotransmission in epilepsy. Epilepsia, 36 (Suppl. 1 (1995) S30–S35.PubMedCrossRefGoogle Scholar
  51. Mink, J.W., The basal ganglia: Focused selection and inhibition of competing motor programs, Prog Neurobiol, 50 (1996) 381–425.PubMedCrossRefGoogle Scholar
  52. Mogenson, G, Jones, D. and Yim, C., From motivation to action: functional interface between the limbic system and the motor system, Prog Neurobiol, 14 (1980) 69–97.PubMedCrossRefGoogle Scholar
  53. Moran, M., O’Connor, W.T., Ungerstedt, U., Bianchi, C. and Fuxe, K., Functional neuroanatomy of the nigrostriatal and striatonigral pathways as studied with dual probe microdialysis in the awake rat.2. Evidence for striatal N-methyl-D-aspartate receptor regulation of striatonigral gabaergic transmission and motor function, Neuroscience, 72 (1996) 89–97.CrossRefGoogle Scholar
  54. Moshe, S.L., Sperber, E.F., Brown, L.L. and Tempel A., Age-dependent changes in the substantia nigra GABA-mediated seizure suppression. In: Avanzini, A., Engel, J., Fariello, R. and Heinemann, U., eds. Neurotransmitter in epilepsy, Epilepsy Res Suppl 8 (1992) 97–106.Google Scholar
  55. Nail-Boucherie, K., Lê-Pham, B.T., Marescaux C., Depaulis A., Suppression of absence seizures by electrical and pharmacological activation of the caudal superior colliculus in a genetic model of absence epilepsy in the rat. Experimental Neurology, in press.Google Scholar
  56. Nehlig, A., Vergnes, M., Marescaux, C. Boyet, S. and Lannes, B., Local cerebral glucose utilization in rats with petit mal-like seizures, Ann Neurol, 29 (1991) 72–77.PubMedCrossRefGoogle Scholar
  57. Niedermeyer, E., Primary (idiopathic) generalized epilepsy and underlying mechanisms, Clin Electroencephal., 27 (1996) 1–21.Google Scholar
  58. Noebels, J.L., Targeting epilepsy genes, Neuron, 16 (1996) 241–244.PubMedCrossRefGoogle Scholar
  59. Phillipson, O. and Griffiths, A., The topographic order of inputs to nucleus accumbens in the rat, Neuroscience, 16 (1985) 275–296.PubMedCrossRefGoogle Scholar
  60. Redgrave, P., Dean, P. and Simkins, M., Intratectal glutamate suppresses pentylenetetrazole-induced spikeand-wave discharges, Eur. J. Pharmac., 158 (1988) 283–287.CrossRefGoogle Scholar
  61. Salamone, J., The behavioral neurochemistry of motivation: methodological and conceptual issues in studies of dynamic activity of nucleus accumbens dopamine, J Neurosci Meth. 64 (1996) 137–149.CrossRefGoogle Scholar
  62. Shehab, S., Simkins, M., Dean, P. and Redgrave, P., The dorsal midbrain anticonvulsant zone-1. Effects of locally administered excitatory amino acids or bicuculline on maximal electroshock seizures. Neuroscience 65 (1995) 671–679PubMedCrossRefGoogle Scholar
  63. Sperk, G., Kainic acid seizures in the rat. Prog Neurobiol 42 (1994) 1–32.PubMedCrossRefGoogle Scholar
  64. Starr, M.S., The role of dopamine in epilepsy, Synapse, 22 (1996) 159–194.PubMedCrossRefGoogle Scholar
  65. Turski, L., Cavalheiro, E.A., Bortolotto, Z.A., Ikonomidou-Turski. C., Kleinrok, Z. and Turski, W.A., Dopamine-sensitive anticonvulsant site in the rat striatum, J. Neurosci., 8 (1988) 3837–3847.Google Scholar
  66. Turski, L., Ikonomidou, C., Turski, W.A., Bortolotto, Z.A. and Cavalheiro, E.A., Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy, Synapse, 3 (1989) 154–171.PubMedCrossRefGoogle Scholar
  67. Turski, L., Meldrum, B.S., Cavalheiro, E.A., Calderazzo-Filho. L.S. Bortolotto, Z.A., Ikonomidou-Turski, C. and Turski, W.A., Paradoxical anticonvulsant activity of the excitatory amino acid N-methyl-Daspartate in the rat caudate-putamen, Proc Nall Acad Sci USA, 84 (1987) 1689–1693.CrossRefGoogle Scholar
  68. Veliskova, J., Velsek, L. and Moshe, S.L., Subthalamic nucleus: A new anticonvulsant site in the brain, Neuroreport, 7 (1996) 1786–1788.PubMedCrossRefGoogle Scholar
  69. Vercueil, L., Benazzouz, A., Deransart, C., Bressand, K., Marescaux. C., Depaulis, A., and Benabid, A.L., High-frequency stimulation of the sub-thalamic nucleus suppressed absence seizures in the rat: comparison with neurotoxic lesions. Epilepsy Res. 31 (1998) 39–46.PubMedCrossRefGoogle Scholar
  70. Vergnes, M., Marescaux, C., Boehrer, A. and Depaulis, A., Are rats with genetic absence epilepsy behaviorally impaired?, Epilepsy Res, 9 (1991) 97–104.PubMedCrossRefGoogle Scholar
  71. Vergnes, M., Marescaux, C. and Depaulis, A., Mapping of spontaneous spike and wave discharges in wistar rats with genetic generalized non convulsive epilepsy, Brain Res, 523 (1990) 87–91.PubMedCrossRefGoogle Scholar
  72. Wahnschaffe, U. and Loscher, W., Selective bilateral destruction of substantia nigra has no effect on kindled seizures induced from stimulation of amygdala or piriform cortex in rats, Neurosci Lett, 113 (1990) 205–210.PubMedCrossRefGoogle Scholar
  73. Wahnschaffe, U. and Loscher, W., Anticonvulsant effects of ipsilateral but not controlateral microinjections of the dopamine D2 agonist LY 171555 into the nucleus accumbens of amygdala-kindled rats, Brain Res, 553 (1991) 181–187.PubMedCrossRefGoogle Scholar
  74. Wafter, J., Vergnes, M., Depaulis, A., Tranchant, C., Rumbach,L., Micheletti, G. and Marescaux, C., Effect of drugs affecting dopaminergic neurotransmission in rats with spontaneous petit mal-like seizures, Neuropharrnacology. 27 (1988) 269–274.CrossRefGoogle Scholar
  75. Wilson, C., Nomikos, G., Collu, M. and Fibiger, H., Doparninergic correlates of motivated behavior: importance of drive, J Neurosci, 15 (1995) 5169–5178.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Colin Deransart
    • 1
  • Véronique Riban
    • 2
  • Laurent Vercueil
    • 2
  • Karine Nail-Boucherie
    • 2
  • Christian Marescaux
    • 2
  • Antoine Depaulis
    • 2
  1. 1.Sektion Klinische NeuropharmakologieKlinikum der Albert-Ludwigs-Universitat NeurozentrumFreiburg im BreisgauGermany
  2. 2.Neurobiologie et neuropharmacologie des epilepsies generalisees INSERM U. 398, Faculte de MedecineStrasbourg CedexFrance

Personalised recommendations