Differential paired-pulse responses between the CA1 region and the dentate gyrus are related to altered CLC-2 immunoreactivity in the pilocarpine-induced rat epilepsy model

The epileptic hippocampus shows differential paired-pulse responses between the dentate gyrus and the CA1 region. However, little data are available to explain this phenomenon. In the present study, we identified the relationship between regional differences of paired-pulse response and voltage gated Cl(-) channel 2 (CLC-2)/vesicular GABA transport (VGAT) expression in a pilocarpine-induced rat model. During epileptogenic periods, paired-pulse inhibitions in the dentate gyrus and the CA1 region were markedly reduced. After recurrent seizure onset, paired-pulse inhibition in the dentate gyrus was markedly enhanced, while that in the CA1 region more reduced. Unlike VGAT, CLC-2 immunoreactivity was markedly reduced in the hippocampus during epileptogenic periods and was re-enhanced only in the dentate gyrus after recurrent seizure onset. Linear regression analysis showed an inverse proportional relationship between alterations in CLC-2 immunoreactivity and changes in normalized population spike amplitude ratio within the CA1 region and the dentate gyrus. Therefore, our findings suggest that the regionally specific alterations in CLC-2 immunoreactivity after SE may determine the properties of paired-pulse responses in the hippocampus of the pilocarpine-induced rat epilepsy model.

[1]  U. Heinemann,et al.  Entorhinal cortex entrains epileptiform activity in CA1 in pilocarpine-treated rats , 2005, Neurobiology of Disease.

[2]  R. S. Sloviter,et al.  Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. , 1987, Science.

[3]  H. Michelson,et al.  Reduction of paired pulse inhibition in the CA1 region of the hippocampus by pilocarpine in naive and in amygdala-kindled rats , 1989, Experimental Neurology.

[4]  E. Cherubini,et al.  Low expression of the ClC-2 chloride channel during postnatal development: a mechanism for the paradoxical depolarizing action of GABA and glycine in the hippocampus , 1999, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[5]  R. Dingledine,et al.  Reduced Excitatory Drive onto Interneurons in the Dentate Gyrus after Status Epilepticus , 2001, The Journal of Neuroscience.

[6]  D. Coulter,et al.  Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy , 1998, Nature Medicine.

[7]  I. Jang,et al.  Contribution of the Na–K–Cl Cotransporter on GABAAReceptor-Mediated Presynaptic Depolarization in Excitatory Nerve Terminals , 2001, The Journal of Neuroscience.

[8]  D. Prince,et al.  Relative contributions of passive equilibrium and active transport to the distribution of chloride in mammalian cortical neurons. , 1988, Journal of neurophysiology.

[9]  E. Lothman,et al.  Dormancy of inhibitory interneurons in a model of temporal lobe epilepsy. , 1993, Science.

[10]  S. Bostel,et al.  Cellular resistance to Evans blue toxicity involves an up‐regulation of a phosphate transporter implicated in vesicular glutamate storage , 2001, Journal of neurochemistry.

[11]  T. Babb,et al.  Circuit Mechanisms of Seizures in the Pilocarpine Model of Chronic Epilepsy: Cell Loss and Mossy Fiber Sprouting , 1993, Epilepsia.

[12]  J. Tepper,et al.  Cell Type-Specific Differences in Chloride-Regulatory Mechanisms and GABAA Receptor-Mediated Inhibition in Rat Substantia Nigra , 2003, The Journal of Neuroscience.

[13]  K. Kaila,et al.  Ionic basis of GABAA receptor channel function in the nervous system , 1994, Progress in Neurobiology.

[14]  Soo‐Young Choi,et al.  Effects of GABAergic transmissions on the immunoreactivities of calcium binding proteins in the gerbil hippocampus , 2005, The Journal of comparative neurology.

[15]  A. Nehlig,et al.  Pharmacological plasticity of GABAA receptors at dentate gyrus synapses in a rat model of temporal lobe epilepsy , 2004 .

[16]  K. Wu,et al.  Increased dendritic excitability in hippocampal ca1 in vivo in the kainic acid model of temporal lobe epilepsy: a study using current source density analysis , 2003, Neuroscience.

[17]  J. Haycock,et al.  Synaptic Vesicle Transporter Expression Regulates Vesicle Phenotype and Quantal Size , 2000, The Journal of Neuroscience.

[18]  H. Dodt,et al.  The role of chloride transport in postsynaptic inhibition of hippocampal neurons. , 1986, Science.

[19]  R. Racine,et al.  Modification of seizure activity by electrical stimulation. II. Motor seizure. , 1972, Electroencephalography and clinical neurophysiology.

[20]  C. Wilcox,et al.  Developmental expression of ClC-2 in the rat nervous system 1 Published on the World Wide Web on 7 A , 1998 .

[21]  I. Módy,et al.  Zinc-Induced Collapse of Augmented Inhibition by GABA in a Temporal Lobe Epilepsy Model , 1996, Science.

[22]  G. Sperk,et al.  Expression of plasma membrane GABA transporters but not of the vesicular GABA transporter in dentate granule cells after kainic acid seizures , 2003, Hippocampus.

[23]  B H Gähwiler,et al.  Activity-dependent disinhibition. II. Effects of extracellular potassium, furosemide, and membrane potential on ECl- in hippocampal CA3 neurons. , 1989, Journal of neurophysiology.

[24]  S. Thompson.  Modulation of inhibitory synaptic transmission in the hippocampus , 1994, Progress in Neurobiology.

[25]  K. Yoo,et al.  Elevated voltage gated Cl− channel expression enhances fast paired-pulse inhibition in the dentate gyrus of seizure sensitive gerbil , 2005, Neuroscience Research.

[26]  Aaron DiAntonio,et al.  Increased Expression of the Drosophila Vesicular Glutamate Transporter Leads to Excess Glutamate Release and a Compensatory Decrease in Quantal Content , 2004, The Journal of Neuroscience.

[27]  L. Sivilotti,et al.  GABA receptor mechanisms in the central nervous system , 1991, Progress in Neurobiology.

[28]  D. Coulter,et al.  Dentate granule cell GABAA receptors in epileptic hippocampus: enhanced synaptic efficacy and altered pharmacology , 2003, The European journal of neuroscience.

[29]  Masayuki Kobayashi,et al.  Reduced Inhibition of Dentate Granule Cells in a Model of Temporal Lobe Epilepsy , 2003, The Journal of Neuroscience.

[30]  J. H. Kim,et al.  Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy , 1989, Brain Research.

[31]  P. Schwartzkroin,et al.  Extracellular chloride and the maintenance of spontaneous epileptiform activity in rat hippocampal slices. , 1999, Journal of neurophysiology.

[32]  A. Obenaus,et al.  Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[33]  C. Marescaux,et al.  Vigabatrin protects against hippocampal damage but is not antiepileptogenic in the lithium-pilocarpine model of temporal lobe epilepsy , 2001, Epilepsy Research.