Skip to main content
Log in

Dysfunction of hippocampal interneurons in epilepsy

  • Review
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Gamma-amino-butyric acid (GABA)-containing interneurons are crucial to both development and function of the brain. Down-regulation of GABAergic inhibition may result in the generation of epileptiform activity. Loss, axonal sprouting, and dysfunction of interneurons are regarded as mechanisms involved in epileptogenesis. Recent evidence suggests that network connectivity and the properties of interneurons are responsible for excitatory-inhibitory neuronal circuits. The balance between excitation and inhibition in CA1 neuronal circuitry is considerably altered during epileptic changes. This review discusses interneuron diversity, the causes of interneuron dysfunction in epilepsy, and the possibility of using GABAergic neuronal progenitors for the treatment of epilepsy.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Freund TF, Buzsaki G. Interneurons of the hippocampus. Hippocampus 1996, 6: 347–470.

    Article  CAS  PubMed  Google Scholar 

  2. Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Wu C. Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 2004, 5: 793–807.

    Article  CAS  PubMed  Google Scholar 

  3. Haider B, Duque A, Hasenstaub AR, McCormick DA. Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition. J Neurosci 2006, 26: 4535–4545.

    Article  CAS  PubMed  Google Scholar 

  4. Klausberger T, Somogyi P. Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations. Science 2008, 321: 53–57.

    Article  CAS  PubMed  Google Scholar 

  5. Marin O. Interneuron dysfunction in psychiatric disorders. Nat Rev Neurosci 2012, 13: 107–120.

    CAS  PubMed  Google Scholar 

  6. Bausch SB. Axonal sprouting of GABAergic interneurons in temporal lobe epilepsy. Epilepsy Behav 2005, 7: 390–400.

    Article  PubMed  Google Scholar 

  7. Ziburkus J, Cressman JR, Barreto E, Schiff SJ. Interneuron and pyramidal cell interplay during in vitro seizure-like events. J Neurophysiol 2006, 95: 3948–3954.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Kumar SS, Buckmaster PS. Hyperexcitability, interneurons, and loss of GABAergic synapses in entorhinal cortex in a model of temporal lobe epilepsy. J Neurosci 2006, 26: 4613–4623.

    Article  CAS  PubMed  Google Scholar 

  9. Wittner L, Eross L, Czirjak S, Halasz P, Freund TF, Magloczky Z. Surviving CA1 pyramidal cells receive intact perisomatic inhibitory input in the human epileptic hippocampus. Brain 2005, 128: 138–152.

    Article  CAS  PubMed  Google Scholar 

  10. Wang Y, Toledo-Rodriguez M, Gupta A, Wu C, Silberberg G, Luo J, et al. Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat. J Physiol 2004, 561: 65–90.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, Wagner-McPherson CB, et al. Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene. Proc Natl Acad Sci U S A 1992, 89: 2115–2119.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Sun Z, Wang HB, Laverghetta A, Yamamoto K, Reiner A. The distribution and cellular localization of glutamic acid decarboxylase-65 (GAD65) mRNA in the forebrain and midbrain of domestic chick. J Chem Neuroanat 2005, 29: 265–281.

    Article  CAS  PubMed  Google Scholar 

  13. McBain CJ, Fisahn A. Interneurons unbound. Nat Rev Neurosci 2001, 2: 11–23.

    Article  CAS  PubMed  Google Scholar 

  14. Armstrong C, Soltesz I. Basket cell dichotomy in microcircuit function. J Physiol 2012, 590: 683–694.

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Freund TF, Katona I. Perisomatic inhibition. Neuron 2007, 56: 33–42.

    Article  CAS  PubMed  Google Scholar 

  16. Bartos M, Elgueta C. Functional characteristics of parvalbumin- and cholecystokinin-expressing basket cells. J Physiol 2012, 590: 669–681.

    CAS  PubMed Central  PubMed  Google Scholar 

  17. Kawaguchi Y, Hama K. Physiological heterogeneity of nonpyramidal cells in rat hippocampal CA1 region. Exp Brain Res 1988, 72: 494–502.

    Article  CAS  PubMed  Google Scholar 

  18. Baraban SC, Southwell DG, Estrada RC, Jones DL, Sebe JY, Alfaro-Cervello C, et al. Reduction of seizures by transplantation of cortical GABAergic interneuron precursors into Kv1.1 mutant mice. Proc Natl Acad Sci U S A 2009, 106: 15472–15477.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Hunt RF, Girskis KM, Rubenstein JL, Alvarez-Buylla A, Baraban SC. GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior. Nat Neurosci 2013.

    Google Scholar 

  20. Song C, Xu XB, He Y, Liu ZP, Wang M, Zhang X, et al. Stuttering interneurons generate fast and robust inhibition onto projection neurons with low capacity of short term modulation in mouse lateral amygdala. PLoS One 2013, 8: e60154.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Faulkner B, Brown T H. Morphology and physiology of neurons in the rat perirhinal-lateral amygdala area. J Comp Neurol 1999, 411: 613–642.

    Article  CAS  PubMed  Google Scholar 

  22. Magloczky Z, Freund TF. Impaired and repaired inhibitory circuits in the epileptic human hippocampus. Trends Neurosci 2005, 28: 334–340.

    Article  CAS  PubMed  Google Scholar 

  23. Cossart R, Bernard C, Ben-Ari Y. Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies. Trends Neurosci 2005, 28: 108–115.

    Article  CAS  PubMed  Google Scholar 

  24. Kriegstein AR. Constructing circuits: neurogenesis and migration in the developing neocortex. Epilepsia 2005, 46Suppl 7: 15–21.

    Article  CAS  PubMed  Google Scholar 

  25. Jiang M, Zhu J, Liu Y, Yang M, Tian C, Jiang S, et al. Enhancement of asynchronous release from fast-spiking interneuron in human and rat epileptic neocortex. PLoS Biol 2012, 10: e1001324.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Morin F, Beaulieu C, Lacaille JC. Cell-specific alterations in synaptic properties of hippocampal CA1 interneurons after kainate treatment. J Neurophysiol 1998, 80: 2836–2847.

    CAS  PubMed  Google Scholar 

  27. Cammarota M, Losi G, Chiavegato A, Zonta M, Carmignoto G. Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy. J Physiol 2013, 591: 807–822.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Arellano JI, Munoz A, Ballesteros-Yanez I, Sola RG, DeFelipe J. Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus. Brain 2004, 127: 45–64.

    Article  CAS  PubMed  Google Scholar 

  29. Andrioli A, Alonso-Nanclares L, Arellano JI, DeFelipe J. Quantitative analysis of parvalbumin-immunoreactive cells in the human epileptic hippocampus. Neuroscience 2007, 149: 131–143.

    Article  CAS  PubMed  Google Scholar 

  30. Dinocourt C, Petanjek Z, Freund TF, Ben-Ari Y, Esclapez M. Loss of interneurons innervating pyramidal cell dendrites and axon initial segments in the CA1 region of the hippocampus following pilocarpine-induced seizures. J Comp Neurol 2003, 459: 407–425.

    Article  PubMed  Google Scholar 

  31. Sloviter RS. 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 1991, 1: 41–66.

    Article  CAS  PubMed  Google Scholar 

  32. Lukasiuk K, Pitkanen A. Gene and protein expression in experimental status epilepticus. Epilepsia 2007, 48Suppl 8: 28–32.

    Article  PubMed  Google Scholar 

  33. Gavrilovici C, Pollock E, Everest M, Poulter MO. The loss of interneuron functional diversity in the piriform cortex after induction of experimental epilepsy. Neurobiol Dis 2012, 48: 317–328.

    Article  PubMed  Google Scholar 

  34. Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A, et al. Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J Neurosci 2000, 20: 9071–9085.

    CAS  PubMed  Google Scholar 

  35. Atzori M, Lau D, Tansey EP, Chow A, Ozaita A, Rudy B, et al. H2 histamine receptor-phosphorylation of Kv3.2 modulates interneuron fast spiking. Nat Neurosci 2000, 3: 791–798.

    Article  CAS  PubMed  Google Scholar 

  36. Dutton SB, Makinson CD, Papale LA, Shankar A, Balakrishnan B, Nakazawa K, et al. Preferential inactivation of Scn1a in parvalbumin interneurons increases seizure susceptibility. Neurobiol Dis 2012, 49C: 211–220.

    Google Scholar 

  37. Magloczky Z, Wittner L, Borhegyi Z, Halasz P, Vajda J, Czirjak S, et al. Changes in the distribution and connectivity of interneurons in the epileptic human dentate gyrus. Neuroscience 2000, 96: 7–25.

    Article  CAS  PubMed  Google Scholar 

  38. Lee J, Park K, Lee S, Whang K, Kang M, Park C, et al. Differential changes of calcium binding proteins in the rat striatum after kainic acid-induced seizure. Neurosci Lett 2002, 333: 87–90.

    Article  CAS  PubMed  Google Scholar 

  39. Sloviter RS, Sollas AL, Barbaro NM, Laxer KD. Calcium-binding protein (calbindin-D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus. J Comp Neurol 1991, 308: 381–396.

    Article  CAS  PubMed  Google Scholar 

  40. Gulyas AI, Megias M, Emri Z, Freund T F. Total number and ratio of excitatory and inhibitory synapses converging onto single interneurons of different types in the CA1 area of the rat hippocampus. J Neurosci 1999, 19: 10082–10097.

    CAS  PubMed  Google Scholar 

  41. Moga D, Hof PR, Vissavajjhala P, Moran TM, Morrison JH. Parvalbumin-containing interneurons in rat hippocampus have an AMPA receptor profile suggestive of vulnerability to excitotoxicity. J Chem Neuroanat 2002, 23: 249–253.

    Article  CAS  PubMed  Google Scholar 

  42. Gruber B, Greber S, Sperk G. Kainic acid seizures cause enhanced expression of cholecystokinin-octapeptide in the cortex and hippocampus of the rat. Synapse 1993, 15: 221–228.

    Article  CAS  PubMed  Google Scholar 

  43. Schwarzer C, Williamson JM, Lothman EW, Vezzani A, Sperk G. Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. Neuroscience 1995, 69: 831–845.

    Article  CAS  PubMed  Google Scholar 

  44. Wyeth MS, Zhang N, Mody I, Houser CR. Selective reduction of cholecystokinin-positive basket cell innervation in a model of temporal lobe epilepsy. J Neurosci 2010, 30: 8993–9006.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Bernard C. Alterations in synaptic function in epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV (Eds.). Jasper’s Basic Mechanisms of the Epilepsies. Bethesda, MD: National Center for Biotechnology Information, 2012.

    Google Scholar 

  46. Sloviter RS, Nilaver G. Immunocytochemical localization of GABA-, cholecystokinin-, vasoactive intestinal polypeptide-, and somatostatin-like immunoreactivity in the area dentata and hippocampus of the rat. J Comp Neurol 1987, 256: 42–60.

    Article  CAS  PubMed  Google Scholar 

  47. Esclapez M, Houser CR. Somatostatin neurons are a subpopulation of GABA neurons in the rat dentate gyrus: evidence from colocalization of pre-prosomatostatin and glutamate decarboxylase messenger RNAs. Neuroscience 1995, 64: 339–355.

    Article  CAS  PubMed  Google Scholar 

  48. Buckmaster PS, Dudek FE. Neuron loss, granule cell axon reorganization, and functional changes in the dentate gyrus of epileptic kainate-treated rats. J Comp Neurol 1997, 385: 385–404.

    Article  CAS  PubMed  Google Scholar 

  49. Kobayashi M, Buckmaster PS. Reduced inhibition of dentate granule cells in a model of temporal lobe epilepsy. J Neurosci 2003, 23: 2440–2452.

    CAS  PubMed  Google Scholar 

  50. Cossart R, Dinocourt C, Hirsch JC, Merchan-Perez A, De Felipe J, Ben-Ari Y, et al. Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy. Nat Neurosci 2001, 4: 52–62.

    Article  CAS  PubMed  Google Scholar 

  51. Sun C, Mtchedlishvili Z, Bertram EH, Erisir A, Kapur J. Selective loss of dentate hilar interneurons contributes to reduced synaptic inhibition of granule cells in an electrical stimulation-based animal model of temporal lobe epilepsy. J Comp Neurol 2007, 500: 876–893.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Mathern GW, Babb TL, Pretorius JK, Leite JP. Rea ctive synaptogenesis and neuron densities for neuropeptide Y, somatostatin, and glutamate decarboxylase immunoreactivity in the epileptogenic human fascia dentata. J Neurosci 1995, 15: 3990–4004.

    CAS  PubMed  Google Scholar 

  53. Park C, Kang M, Kang K, Lee J, Kim J, Yoo J, et al. Differential changes in neuropeptide Y and nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons in rat hippocampus after kainic acid-induced seizure. Neurosci Lett 2001, 298: 49–52.

    Article  CAS  PubMed  Google Scholar 

  54. Kuruba R, Hattiangady B, Parihar VK, Shuai B, Shetty AK. Differential susceptibility of interneurons expressing neuropeptide Y or parvalbumin in the aged hippocampus to acute seizure activity. PLoS One 2011, 6: e24493.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Sloviter RS, Zappone CA, Harvey BD, Bumanglag AV, Bender RA, Frotscher M. “Dormant basket cell” hypothesis revisited: relative vulnerabilities of dentate gyrus mossy cells and inhibitory interneurons after hippocampal status epilepticus in the rat. J Comp Neurol 2003, 459: 44–76.

    Article  CAS  PubMed  Google Scholar 

  56. de Lanerolle NC, Gunel M, Sundaresan S, Shen MY, Brines ML, Spencer DD. Vasoactive intestinal polypeptide and its receptor changes in human temporal lobe epilepsy. Brain Res 1995, 686: 182–193.

    Article  PubMed  Google Scholar 

  57. King JT, Jr., LaMotte CC. VIP-, SS-, and GABA-like immunoreactivity in the mid-hippocampal region of El (epileptic) and C57BL/6 mice. Brain Res 1988, 475: 192–197.

    Article  PubMed  Google Scholar 

  58. Marksteiner J, Sperk G, Maas D. Differential increases in brain levels of neuropeptide Y and vasoactive intestinal polypeptide after kainic acid-induced seizures in the rat. Naunyn Schmiedebergs Arch Pharmacol 1989, 339: 173–177.

    CAS  PubMed  Google Scholar 

  59. Hou YC, Janczuk A, Wang PG. Current trends in the development of nitric oxide donors. Curr Pharm Des 1999, 5: 417–441.

    CAS  PubMed  Google Scholar 

  60. del Zoppo G, Ginis I, Hallenbeck JM, Iadecola C, Wang XK, Feuerstein GZ. Inflammation and stroke: Putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain pathology 2000, 10: 95–112.

    Article  PubMed  Google Scholar 

  61. Jinno S, Kosaka T. Cellular architecture of the mouse hippocampus: a quantitative aspect of chemically defined GABAergic neurons with stereology. Neurosci Res 2006, 56: 229–245.

    Article  CAS  PubMed  Google Scholar 

  62. Gonzalez-Hernandez T, Garcia-Marin V, Perez-Delgado MM, Gonzalez-Gonzalez ML, Rancel-Torres N, Gonzalez-Feria L. Nitric oxide synthase expression in the cerebral cortex of patients with epilepsy. Epilepsia 2000, 41: 1259–1268.

    Article  CAS  PubMed  Google Scholar 

  63. Beamer E, Otahal J, Sills GJ, Thippeswamy T. N (w)-propyl-L-arginine (L-NPA) reduces status epilepticus and early epileptogenic events in a mouse model of epilepsy: behavioural, EEG and immunohistochemical analyses. Eur J Neurosci 2012, 36: 3194–3203.

    Article  PubMed  Google Scholar 

  64. Leite JP, Chimelli L, Terra-Bustamante VC, Costa ET, Assirati JA, de Nucci G, et al. Loss and sprouting of nitric oxide synthase neurons in the human epileptic hippocampus. Epilepsia 2002, 43Suppl 5: 235–242.

    Article  CAS  PubMed  Google Scholar 

  65. Montecot C, Rondi-Reig L, Springhetti V, Seylaz J, Pinard E. Inhibition of neuronal (type 1) nitric oxide synthase prevents hyperaemia and hippocampal lesions resulting from kainateinduced seizures. Neuroscience 1998, 84: 791–800.

    Article  CAS  PubMed  Google Scholar 

  66. Lumme A, Soinila S, Sadeniemi M, Halonen T, Vanhatalo S. Nitric oxide synthase immunoreactivity in the rat hippocampus after status epilepticus induced by perforant pathway stimulation. Brain Research 2000, 871: 303–310.

    Article  CAS  PubMed  Google Scholar 

  67. Liang Z, Zhang L, Wang X, Gao F, Wang X, Zhou S, et al. Distribution and neurochemical features of neuronal nitric oxide synthase-expressing interneurons in the rat dentate gyrus. Brain Research 2013, 1505: 11–21.

    Article  CAS  PubMed  Google Scholar 

  68. Slaght SJ, Paz T, Chavez M, Deniau JM, Mahon S, Charpier S. On the activity of the corticostriatal networks during spike-and-wave discharges in a genetic model of absence epilepsy. J Neurosci 2004, 24: 6816–6825.

    Article  CAS  PubMed  Google Scholar 

  69. Maheshwari A, Nahm WK, Noebels JL. Paradoxical proepileptic resp onse to NMDA receptor blockade linked to cortical interneuron defect in stargazer mice. Front Cell Neurosci 2013, 7: 156.

    Article  PubMed Central  PubMed  Google Scholar 

  70. Sitnikova E. Thalamo-cortical mechanisms of sleep spindles and spike-wave discharges in rat model of absence epilepsy (a review). Epilepsy Res 2010, 89: 17–26.

    Article  PubMed  Google Scholar 

  71. Zhang W, Yamawaki R, Wen X, Uhl J, Diaz J, Prince DA, et al. Surviving hilar somatostatin interneurons enlarge, sprout axons, and form new synapses with granule cells in a mouse model of temporal lobe epilepsy. J Neurosci 2009, 29: 14247–14256.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Lowenstein DH, Bleck T, Macdonald RL. It’s time to revise the definition of status epilepticus. Epilepsia 1999, 40: 120–122.

    Article  CAS  PubMed  Google Scholar 

  73. Doherty J, Dingledine R. Reduced excitatory drive onto interneurons in the dentate gyrus after status epilepticus. J Neurosci 2001, 21: 2048–2057.

    CAS  PubMed  Google Scholar 

  74. Hellier JL, Patrylo PR, Dou P, Nett M, Rose GM, Dudek FE. Assessment of inhibition and epileptiform activity in the septal dentate gyrus of freely behaving rats during the first week after kainate treatment. J Neurosci 1999, 19: 10053–10064.

    CAS  PubMed  Google Scholar 

  75. Paul LA, Fried I, Watanabe K, Forsythe AB, Scheibel AB. Structural co rrelates of seizure behavior in the mongolian gerbil. Science 1981, 213: 924–926.

    Article  CAS  PubMed  Google Scholar 

  76. Rogawski MA, Loscher W. The neurobiology of antiepileptic drugs. Nat Rev Neurosci 2004, 5: 553–564.

    Article  CAS  PubMed  Google Scholar 

  77. Toda Y, Kobayashi K, Hayashi Y, Inoue T, Oka M, Ohtsuka Y. Effects of intravenous diazepam on high-frequency oscillations in EEGs with CSWS. Brain Dev 2013, 35: 540–547.

    Article  PubMed  Google Scholar 

  78. Braga MF, Aroniadou-Anderjaska V, Li H, Rogawski MA. Topiramate reduces excitability in the basolateral amygdala by selectively inhibiting GluK1 (GluR5) kainate receptors on interneurons and positively modulating GABAA receptors on principal neurons. J Pharmacol Exp Ther 2009, 330: 558–566.

    Article  CAS  PubMed  Google Scholar 

  79. Peng BW, Justice JA, Zhang K, Li JX, He XH, Sanchez RM. Gabapentin promot es inhibition by enhancing hyperpolarization-activatedcation currents and spontaneous firing in hippocampal CA1 interneurons. Neurosci Lett 2011, 494: 19–23.

    Article  CAS  PubMed  Google Scholar 

  80. Peng BW, Justice JA, Zhang K, He XH, Sanchez RM. Increased Basal Synaptic Inhibition of Hippocampal Area CA1 Pyramidal Neurons by an Antiepileptic Drug that Enhances I-H. Neuropsychopharmacology 2010, 35: 464–472.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Huang X, Zhang H, Yang J, Wu J, McMahon J, Lin Y, et al. Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy. Neurobiol Dis 2010, 40: 193–199.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Buckmaster PS, Wen X. Rapamycin suppresses axon sprouting by somatostatin interneurons in a mouse model of temporal lobe epilepsy. Epilepsia 2011, 52: 2057–2064.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Ylinen A, Valjakka A, Lahtinen H, Miettinen R, Freund TF, Riekkinen P. Vigabatrin pre-treatment prevents hilar somatostatin cell loss and the development of interictal spiking activity following sustained simulation of the perforant path. Neuropeptides 1991, 19: 205–211.

    Article  CAS  PubMed  Google Scholar 

  84. Kaputlu I, Uzbay T. L-NAME inhibits pentylenetetrazole and strychnine-induced seizures in mice. Brain Res 1997, 753: 98–101.

    Article  CAS  PubMed  Google Scholar 

  85. Broicher T, Seidenbecher T, Meuth P, Munsch T, Meuth SG, Kanyshkova T, et al. T-current related effects of antiepileptic drugs and a Ca2+ channel antagonist on thalamic relay and local circuit interneurons in a rat model of absence epilepsy. Neuropharmacology 2007, 53: 431–446.

    Article  CAS  PubMed  Google Scholar 

  86. Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol 2012, 11: 792–802.

    Article  CAS  PubMed  Google Scholar 

  87. Arber C, Li M. Cortical interneurons from human pluripotent stem cells: prospects for neurological and psychiatric disease. Front Cell Neurosci 2013, 7: 10.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Chu K, Kim M, Jung KH, Jeon D, Lee ST, Kim J, et al. Human neural stem cell trans plantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats. Brain Res 2004, 1023: 213–221.

    Article  CAS  PubMed  Google Scholar 

  89. Shetty AK, Hattiangady B. Restoration of calbindin after fetal hippocampal CA3 cell grafting into the injured hippocampus in a rat model of temporal lobe epilepsy. Hippocampus 2007, 17: 943–956.

    Article  PubMed Central  PubMed  Google Scholar 

  90. Shetty AK, Turner DA. Fetal hippocampal grafts containing CA3 cells restore host hippocampal glutamate decarboxylase-positive interneuron numbers in a rat model of temporal lobe epilepsy. J Neurosci 2000, 20: 8788–8801.

    CAS  PubMed  Google Scholar 

  91. Zipancic I, Calcagnotto ME, Piquer-Gil M, Mello LE, Alvarez-Dolado M. Transplant of GABAergic precursors restores hippocampal inhibitory function in a mouse model of seizure susceptibility. Cell Transplant 2010, 19: 549–564.

    Article  CAS  PubMed  Google Scholar 

  92. Sebe JY, Baraban SC. The promise of an interneuron-based cell therapy for epilepsy. Dev Neurobiol 2011, 71: 107–117.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bi-Wen Peng.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, YQ., Yu, F., Liu, WH. et al. Dysfunction of hippocampal interneurons in epilepsy. Neurosci. Bull. 30, 985–998 (2014). https://doi.org/10.1007/s12264-014-1478-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-014-1478-4

Keywords

Navigation