Injury Induced Epileptogenesis: Contribution of Active Inhibition, Disfacilitation and Deafferentation to Seizure Induction in Thalamocortical System

Chapter

Abstract

Neocortical seizures are the seizures in which neocortex is the leading structure. They are characterized by spike-wave (SW) or spike-wave/polyspike-wave (SW/PSW) complexes of 1.5–3 Hz, intermingled with episodes of fast runs at ∼10–20 Hz. These seizures often develop during slow-wave sleep, transition from wake to slow-wave sleep or transition from slow-wave sleep to waking state. Intracellular studies on both anesthetized and non-anesthetized cats have shown that hyperpolarizing phase of the slow oscillation, a distinct feature of slow-wave sleep, is associated with disfacilitation, a temporal absence of synaptic activity in all cortical neurons. Periods of disfacilitation temporally increase network excitability. The hyperpolarizing components of SW-PSW complexes are mediated mainly by leak current (state similar to discfacilitation), Ca2+- and Na+-activated K+ currents. It is proposed that prolonged periods of disfacilitation up-regulate neuronal excitability that contributes to the seizure generation. Once seizure has started, fast-spiking inhibitory interneurons fire multiple action potentials during paroxysmal depolarizing shifts (EEG spike components of SW/PSW complexes). During seizure a set of cellular processes induces a shift of reversal potential of GABA toward depolarization. Intense firing of GABAergic neurons and depolarizing GABA responses largely contribute to the generation of paroxysmal EEG spikes. Inhibition does not play a role in other components of neocortical seizures. Neocortical trauma, in particular penetrating wounds, produces partial deafferentation of a subset of neurons that decreases excitability of network. Cortical neurons display occasional periods of disfacilitation in deafferented cortex during all states of vigilance. As in the case of slow-wave sleep, periods of disfacilitation up-regulate neuronal excitability. Synaptic volleys originating from preserved axons impinge hyperexcitable neurons of deafferented cortex that trigger seizures. I propose that any physiological or pathological condition that leads to repeated or prolonged periods of neuronal silence will increase neuronal hyperexcitability that favours development of seizures.

Keywords

Depression Undercut 

Notes

Acknowledgments

My research is supported by Canadian Institutes of Health Research, National Institutes of Health, Fonds de la Recherche en Santé du Québec and Natural Science and Engineering Research Council of Canada.

References

  1. Abbott LF, Varela JA, Sen K, Nelson SB (1997) Synaptic depression and cortical gain control. Science 275:220–224.Google Scholar
  2. Annegers JF, Hauser WA, Coan SP, Rocca WA (1998) A population-based study of seizures after traumatic brain injuries. N Engl J Med 338:20–24.PubMedCrossRefGoogle Scholar
  3. Avramescu S, Timofeev I (2008) Synaptic strength modulation following cortical trauma: a role in epileptogenesis. J Neurosci 28:6760–6772.PubMedCrossRefGoogle Scholar
  4. Avramescu S, Nita D, Timofeev I (2009) Neocortical post-traumatic epileptogenesis is associated with the loss of GABAergic neurons. J Neurotrauma 26:799–812.PubMedCrossRefGoogle Scholar
  5. Bazhenov M, Timofeev I (2006) Thalamocortical oscillations.Google Scholar
  6. Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ (2004) Potassium model for slow (2–3 Hz) in vivo neocortical paroxysmal oscillations. J Neurophysiol 92:1116–1132.PubMedCrossRefGoogle Scholar
  7. Blake H, Gerard RW (1937) Brain potentials during sleep. Am J Physiol 119:692–703.Google Scholar
  8. Boucetta S, Crochet S, Timofeev I (2003) Effects of extracellular Ca 2+ concentration on ­firing properties of cortical neurons. In: SFN annual meeting, p Program No. 791.796. New Orleans.Google Scholar
  9. Boucetta S, Chauvette S, Bazhenov M, Timofeev I (2008) Focal generation of paroxysmal fast runs during electrographic seizures. Epilepsia 49:1925–1940.PubMedCrossRefGoogle Scholar
  10. Brailowsky S, Kunimoto M, Menini C, Silva-Barrat C, Riche D, Naquet R (1988) The GABA-withdrawal syndrome: a new model of focal epileptogenesis. Brain Res 442:175–179.Google Scholar
  11. Brailowsky S, Silva-Barrat C, Menini C, Riche D, Naquet R (1989) Effects of localized, chronic GABA infusions into different cortical areas of the photosensitive baboon, Papio papio. Electroencephalogr Clin Neurophysiol 72:147–156.Google Scholar
  12. Chang BS, Lowenstein DH (2003) Practice parameter: antiepileptic drug prophylaxis in severe traumatic brain injury: report of the quality standards subcommittee of the American academy of neurology. Neurology 60:10–16.PubMedGoogle Scholar
  13. Cohen I, Navarro V, Clemenceau S, Baulac M, Miles R (2002) On the origin of interictal activity in human temporal lobe epilepsy in vitro. Science 298:1418–1421.PubMedCrossRefGoogle Scholar
  14. Contreras D, Steriade M (1995) Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic relationships. J Neurosci 15:604–622.PubMedGoogle Scholar
  15. Contreras D, Timofeev I, Steriade M (1996) Mechanisms of long-lasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks. J Physiol 494:251–264.PubMedGoogle Scholar
  16. Crochet S, Petersen CC (2006) Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nat Neurosci 9:608–610.PubMedCrossRefGoogle Scholar
  17. Crochet S, Chauvette S, Boucetta S, Timofeev I (2005) Modulation of synaptic transmission in neocortex by network activities. Eur J Neurosci 21:1030–1044.PubMedCrossRefGoogle Scholar
  18. Crunelli V, Leresche N (2002) Childhood absence epilepsy: genes, channels, neurons and networks. Nat Rev Neurosci 3:371–382.Google Scholar
  19. D Ambrosio R, Fairbanks JP, Fender JS, Born DE, Doyle DL, Miller JW (2004) Post-traumatic epilepsy following fluid percussion injury in the rat. Brain 127:304–314.PubMedCrossRefGoogle Scholar
  20. Desai NS, Nelson SB, Turrigiano GG (1999) Activity-dependent regulation of excitability in rat visual cortical neurons. Neurocomputing 26–27:101–106.Google Scholar
  21. Desai NS, Rutherford LC, Turrigiano GG (1999) Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nature Neuroscience 2:515–520.PubMedCrossRefGoogle Scholar
  22. Dinner D (1993) Posttraumatic epilepsy. In: The Treatment of Epilepsy: Principles (E. W, ed), pp 654–658. Philadelphia: Lea & Fibinger.Google Scholar
  23. Echlin FA, Battista A (1963) Epileptiform seizures from chronic isolated cortex. Arch Neurol 168:154–170.Google Scholar
  24. Echlin FA, Arnet V, Zoll J (1952) Paroxysmal high voltage discharges from isolated and partially isolated human and animal cerebral cortex. Electroencephalogr Clin Neurophysiol 4:147–164.PubMedCrossRefGoogle Scholar
  25. Feeney DM, Walker AE (1979) The prediction of posttraumatic epilepsy. A mathematical approach. Arch Neurol 36:8–12.PubMedGoogle Scholar
  26. Galarreta M, Hestrin S (1998) Frequency-dependent synaptic depression and the balance of excitation and inhibition in the neocortex. Nat Neurosci 1:587–594.PubMedCrossRefGoogle Scholar
  27. Gentet LJ, Avermann M, Matyas F, Staiger JF, Petersen CCH (2010) Membrane potential dynamics of GABAergic neurons in the barrel cortex of behaving mice. Neuron 65:422–435.PubMedCrossRefGoogle Scholar
  28. Grenier F, Timofeev I, Steriade M (2001) Focal synchronization of ripples (80–200 Hz) in neocortex and their neuronal correlates. J Neurophysiol 86:1884–1898.PubMedGoogle Scholar
  29. Grenier F, Timofeev I, Steriade M (2003a) Neocortical very fast oscillations (ripples, 80–200 Hz) during seizures: intracellular correlates. J Neurophysiol 89:841–852.PubMedCrossRefGoogle Scholar
  30. Grenier F, Timofeev I, Crochet S, Steriade M (2003b) Spontaneous field potentials influence the activity of neocortical neurons during paroxysmal activities in vivo. Neuroscience 119:277–291.PubMedCrossRefGoogle Scholar
  31. Haider B, McCormick DA (2009) Rapid neocortical dynamics: cellular and network mechanisms. Neuron 62:171–189.PubMedCrossRefGoogle Scholar
  32. Hoffman SN, Salin PA, Prince DA (1994) Chronic neocortical epileptogenesis in vitro. J Neurophysiol 71:1762–1773.PubMedGoogle Scholar
  33. Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ (2005) Homeostatic synaptic plasticity can explain post-traumatic epileptogenesis in chronically isolated neocortex. Cereb Cortex 15:834–845.PubMedCrossRefGoogle Scholar
  34. Jacobs KM, Graber KD, Kharazia VN, Parada I, Prince DA (2000) Postlesional epilepsy: the ultimate brain plasticity. Epilepsia 41 Suppl 6:S153-S161.PubMedCrossRefGoogle Scholar
  35. Jacobs KM, Prince DA (2005) Excitatory and inhibitory postsynaptic currents in a rat model of epileptogenic microgyria. J Neurophysiol 93:687–696.Google Scholar
  36. Jin X, Huguenard JR, Prince DA (2005) Impaired Cl extrusion in layer V pyramidal neurons of chronically injured epileptogenic neocortex. J Neurophysiol 93:2117–2126.PubMedCrossRefGoogle Scholar
  37. Jin X, Prince DA, Huguenard JR (2006) Enhanced excitatory synaptic connectivity in layer V pyramidal neurons of chronically injured epileptogenic neocortex in rats. J Neurosci 26:4891–4900.PubMedCrossRefGoogle Scholar
  38. Kollevold T (1976) Immediate and early cerebral seizures after head injuries. Part I. J Oslo City Hosp 26:99–114.PubMedGoogle Scholar
  39. Li H, Prince DA (2002) Synaptic activity in chronically injured, epileptogenic sensory-motor neocortex. J Neurophysiol 88:2–12.PubMedGoogle Scholar
  40. Li H, Bandrowski AE, Prince DA (2005) Cortical injury affects short-term plasticity of evoked excitatory synaptic currents. J Neurophysiol 93:146–156.PubMedCrossRefGoogle Scholar
  41. Mahon S, Vautrelle N, Pezard L, Slaght SJ, Deniau J-M, Chouvet G, Charpier S (2006) Distinct patterns of striatal medium spiny neuron activity during the natural sleep-wake cycle. J Neurosci 26:12587–12595.PubMedCrossRefGoogle Scholar
  42. Marcikic M, Melada A, Kovacevic R (1998) Management of war penetrating craniocerebral injuries during the war in Croatia. Injury 29:613–618.PubMedCrossRefGoogle Scholar
  43. Massimini M, Amzica F (2001) Extracellular calcium fluctuations and intracellular potentials in the cortex during the slow sleep oscillation. J Neurophysiol 85:1346–1350.PubMedGoogle Scholar
  44. McNamara JO (1994) Cellular and molecular basis of epilepsy. J Neurosci 14:3413–3425.Google Scholar
  45. Meeren HK, Pijn JP, Van Luijtelaar EL, Coenen AM, Lopes da Silva FH (2002) Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. J Neurosci 22:1480–1495.Google Scholar
  46. Messori A, Polonara G, Carle F, Gesuita R, Salvolini U (2005) Predicting posttraumatic epilepsy with MRI: prospective longitudinal morphologic study in adults. Epilepsia 46:1472–1481.PubMedCrossRefGoogle Scholar
  47. Moody WJ, Futamachi KJ, Prince DA (1974) Extracellular potassium activity during epileptogenesis. Exp Neurol 42:248–263.PubMedCrossRefGoogle Scholar
  48. Moruzzi G, Magoun HW (1949) Brain stem reticular formation and activation of the EEG. Electroencephalogr Clin Neurophysiol 1:455–473.PubMedGoogle Scholar
  49. Mukovski M, Chauvette S, Timofeev I, Volgushev M (2007) Detection of active and silent states in neocortical neurons from the field potential signal during slow-wave sleep. Cereb Cortex 17:400–414.PubMedCrossRefGoogle Scholar
  50. Murthy VN, Schikorski T, Stevens CF, Zhu Y (2001) Inactivity produces increases in neurotransmitter release and synapse size. Neuron 32:673–682.Google Scholar
  51. Neckelmann D, Amzica F, Steriade M (1998) Spike-wave complexes and fast components of cortically generated seizures. III. Synchronizing mechanisms. J Neurophysiol 80:1480–1494.Google Scholar
  52. Niedermeyer E (2005) Abnormal EEG patterns: epileptic and paroxysmal. In: Electroencephalo­graphy: Basic Principles, Clinical Applications, and Related Fields, Fifth Edition Edition (Niedermeyer E, Lopes de Silva F, eds), pp 255–280. Philadelphia: Lippincott Williams & Wilkins.Google Scholar
  53. Nita D, Cisse Y, Timofeev I (2008a) State-dependent slow outlasting activities following neocortical kindling in cats. Exp Neurol 211:456–468.PubMedCrossRefGoogle Scholar
  54. Nita D, Cissé Y, Timofeev I, Steriade M (2006) Increased propensity to seizures after chronic cortical deafferentation in vivo. J Neurophysiol 95:902–913.PubMedCrossRefGoogle Scholar
  55. Nita D, Cisse Y, Frohlich F, Timofeev I (2008b) Cortical and thalamic components of neocortical kindling-induced epileptogenesis in behaving cats. Exp Neurol 211:518–528.PubMedCrossRefGoogle Scholar
  56. Nita DA, Cisse Y, Timofeev I, Steriade M (2007) Waking-sleep modulation of paroxysmal activities induced by partial cortical deafferentation. Cereb Cortex 17:272–283.PubMedCrossRefGoogle Scholar
  57. Pinault D, Leresche N, Charpier S, Deniau JM, Marescaux C, Vergnes M, Crunelli V (1998) Intracellular recordings in thalamic neurones during spontaneous spike and wave discharges in rats with absence epilepsy. J Physiol 509:449–456.PubMedCrossRefGoogle Scholar
  58. Polack P-O, Charpier S (2006) Intracellular activity of cortical and thalamic neurones during high-voltage rhythmic spike discharge in Long-Evans rats in vivo. J Physiol 571:461–476.PubMedCrossRefGoogle Scholar
  59. Poulet JFA, Petersen CCH (2008) Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454:881–885.PubMedCrossRefGoogle Scholar
  60. Prince DA, Tseng GF (1993) Epileptogenesis in chronically injured cortex: in vitro studies. J Neurophysiol 69:1276–1291.Google Scholar
  61. Prince DA, Jacobs KM, Salin PA, Hoffman S, Parada I (1997) Chronic focal neocortical epileptogenesis: does disinhibition play a role? Can J Physiol Pharmacol 75:500–507.PubMedCrossRefGoogle Scholar
  62. Pumain R, Kurcewicz I, Louvel J (1983) Fast extracellular calcium transients: involvement in epileptic processes. Science 222:177–179.PubMedCrossRefGoogle Scholar
  63. Rudolph M, Pospischil M, Timofeev I, Destexhe A (2007) Inhibition determines membrane potential dynamics and controls action potential generation in awake and sleeping cat cortex. J Neurosci 27:5280–5290.PubMedCrossRefGoogle Scholar
  64. Sakowitz OW, Unterberg AW, Stover JF (2002) Neuronal activity determined by quantitative EEG and cortical microdialysis is increased following controlled cortical impact injury in rats. Acta Neurochir Suppl 81:221–223.PubMedGoogle Scholar
  65. Salazar A, Jabbari B, Vance S, Grafman J, Amin D, Dillon J (1985) Epilepsy after penetrating head injury. I. Clinical correlates: a report of the Vietnam Head Injury Study. Neurology 35:1406–1414.PubMedGoogle Scholar
  66. Salin P, Tseng G-F, Hoffman S, Parada I, Prince DA (1995) Axonal sprouting in layer V pyramidal neurons of chronically injured cerebral cortex. J Neurosci 15:8234–8245.PubMedGoogle Scholar
  67. Sharpless SK (1969) Isolated and deafferented neurons: diffuse supersensitivity. In: Basic Mechanisms of the Epilepsies (Jasper H WA, and Pope A, ed), pp 329–348. Boston, MA: Little Brown.Google Scholar
  68. Sharpless SK, Halpern LM (1962) The electrical excitability of chronically isolated cortex studied by means of permanently implanted electrodes. Electroencephalogr Clin Neurophysiol 14:244–255.PubMedCrossRefGoogle Scholar
  69. Shu Y, Hasenstaub A, McCormick DA (2003) Turning on and off recurrent balanced cortical activity. Nature 423:288–293.PubMedCrossRefGoogle Scholar
  70. Silva-Barrat C, Araneda S, Menini C, Champagnat J, Naquet R (1992) Burst generation in neocortical neurons after GABA withdrawal in the rat. J Neurophysiol 67:715–727.Google Scholar
  71. Steriade M, Contreras D (1995) Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity. J Neurosci 15:623–642.PubMedGoogle Scholar
  72. Steriade M, Contreras D (1998) Spike-wave complexes and fast components of cortically generated seizures. I. Role of neocortex and thalamus. J Neurophysiol 80:1439–1455.Google Scholar
  73. Steriade M, Timofeev I, Grenier F (2001) Natural waking and sleep states: a view from inside neocortical neurons. J Neurophysiol 85:1969–1985.PubMedGoogle Scholar
  74. Steriade M, Amzica F, Neckelmann D, Timofeev I (1998) Spike-wave complexes and fast components of cortically generated seizures. II. Extra- and intracellular patterns. J Neurophysiol 80:1456–1479.PubMedGoogle Scholar
  75. Temkin NR, Haglund MM, Winn HR (1995) Causes, prevention, and treatment of post-traumatic epilepsy. New Horiz 3:518–522.PubMedGoogle Scholar
  76. Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR (1990) A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med 323:497–502.PubMedCrossRefGoogle Scholar
  77. Temkin NR, Dikmen SS, Anderson GD, Wilensky AJ, Holmes MD, Cohen W, Newell DW, Nelson P, Awan A, Winn HR (1999) Valproate therapy for prevention of posttraumatic seizures: a randomized trial. J Neurosurg 91:593–600.PubMedCrossRefGoogle Scholar
  78. Thimm J, Mechler A, Lin H, Rhee S, Lal R (2005) Calcium-dependent open/closed conformations and interfacial energy maps of reconstituted hemichannels. J Biol Chem 280:10646–10654.PubMedCrossRefGoogle Scholar
  79. Timofeev I (2010) Pathophysiology of neocortical seizures. In: The Atlas of Epilepsies (Panayiotopoulos CP, ed), p in press. London: Springer-Verlag.Google Scholar
  80. Timofeev I, Steriade M (2004) Neocortical seizures: initiation, development and cessation. Neuroscience 123:299–336.PubMedCrossRefGoogle Scholar
  81. Timofeev I, Bazhenov M (2005) Mechanisms of cortical trauma induced epileptogenesis and seizures. In: Recent Res. Devel. Physiol. (Pandalai SG, ed), pp 99–139. Kerala, India: Research Signpost.Google Scholar
  82. Timofeev I, Bazhenov M, Sejnowski T, Steriade M (2002) Cortical hyperpolarization-activated depolarizing current takes part in the generation of focal paroxysmal activities. Proc Natl Acad Sci USA 99:9533–9537.Google Scholar
  83. Timofeev I, Contreras D, Steriade M (1996) Synaptic responsiveness of cortical and thalamic neurones during various phases of slow sleep oscillation in cat. J Physiol 494:265–278.PubMedGoogle Scholar
  84. Timofeev I, Grenier F, Steriade M (1998) Spike-wave complexes and fast components of cortically generated seizures. IV. Paroxysmal fast runs in cortical and thalamic neurons. J Neurophysiol 80:1495–1513.PubMedGoogle Scholar
  85. Timofeev I, Grenier F, Steriade M (2000a) Impact of intrinsic properties and synaptic factors on the activity of neocortical networks in vivo. J Physiol (Paris) 94:343–355.CrossRefGoogle Scholar
  86. Timofeev I, Grenier F, Steriade M (2001) Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: An intracellular study. Proc Natl Acad Sci USA 98:1924–1929.PubMedCrossRefGoogle Scholar
  87. Timofeev I, Grenier F, Steriade M (2002) The role of chloride-dependent inhibition and the activity of fast-spiking neurons during cortical spike-wave seizures. Neuroscience 114:1115–1132.PubMedGoogle Scholar
  88. Timofeev I, Grenier F, Steriade M (2004) Contribution of intrinsic neuronal factors in the generation of cortically driven electrographic seizures. J Neurophysiol 92:1133–1143.PubMedCrossRefGoogle Scholar
  89. Timofeev I, Bazhenov M, Avramescu S, Nita DA (2010) Posttraumatic epilepsy: the roles of synaptic plasticity. Neuroscientist 16:19–27.PubMedCrossRefGoogle Scholar
  90. Timofeev I, Grenier F, Bazhenov M, Sejnowski TJ, Steriade M (2000b) Origin of slow cortical oscillations in deafferented cortical slabs. Cereb Cortex 10:1185–1199.PubMedCrossRefGoogle Scholar
  91. Topolnik L, Steriade M, Timofeev I (2003a) Partial cortical deafferentation promotes development of paroxysmal activity. Cereb Cortex 13:883–893.PubMedCrossRefGoogle Scholar
  92. Topolnik L, Steriade M, Timofeev I (2003b) Hyperexcitability of intact neurons underlies acute development of trauma-related electrographic seizures in cats in vivo. Eur J Neurosci 18:486–496.PubMedCrossRefGoogle Scholar
  93. Traynelis SF, Dingledine R (1988) Potassium-induced spontaneous electrographic seizures in the rat hippocampal slice. J Neurophysiol 59:259–276.PubMedGoogle Scholar
  94. Tseng G-F, Prince DA (1996) Structural and functional alterations in rat corticospinal neurons after axotomy. J Neurophysiol 75:248–267.Google Scholar
  95. Turrigiano GG (1999) Homeostatic plasticity in neuronal networks: the more things change, the more they stay the same. Trends Neurosci 22:221–227.PubMedCrossRefGoogle Scholar
  96. Turrigiano GG, Leslie KR, Desai NS, Rutherford LC, Nelson SB (1998) Activity-dependent scaling of quantal amplitude in neocortical neurons. Nature 391:892–896.PubMedCrossRefGoogle Scholar
  97. Willmore LJ, Sypert GW, Munson JV, Hurd RW (1978) Chronic focal epileptiform discharges induced by injection of iron into rat and cat cortex. Science 200:1501–1503.PubMedCrossRefGoogle Scholar
  98. Zhang F, Wang LP, Boyden ES, Deisseroth K (2006) Channelrhodopsin-2 and optical control of excitable cells. Nat Methods 3:785–792.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Psychiatry and Neuroscience, Laval UniversityThe Centre de recherche Université Laval Robert-Giffard (CRULRG)QuébecCanada

Personalised recommendations