Progression of temporal lobe epilepsy in the rat is associated with immunocytochemical changes in inhibitory interneurons in specific regions of the hippocampal formation

Immunocytochemical markers of specific rat hippocampal interneuron subpopulations, including the calcium binding proteins parvalbumin (PV), and calretinin (CR) were examined in relation to the evolution of spontaneous seizures after electrically induced status epilepticus (SE). PV/CR/NeuN immunoreactive neurons were counted in the hippocampal formation at different time intervals after SE and related to spontaneous hippocampal discharge activity. Decreased PV immunoreactivity was observed within 1 day after SE in the hilus, pre- and parasubiculum, and in the entorhinal cortex layers II and V/VI. In layer III, the density of detectable PV immunoreactive neurons did not decrease significantly, whereas the number of surrounding principal neurons was extensively decreased within a week in most post-SE rats, and after 3-4.5 months in all rats that had developed a progressive evolution of seizures. CR immunoreactive neuron number decreased in all hippocampal subregions except for the stratum lacunosum-moleculare and the EC layer II, in which the density did not decrease significantly. The apparent decrease in the number of PV and CR immunoreactive hilar neurons was correlated with the duration of the SE and was most extensive in rats with a progressive form of epilepsy. The loss of CR and PV expression or the loss of CR- and PV-containing neurons in specific regions of the hippocampal formation may play a role in the progressive nature of epilepsy possibly via increasing the entorhinal-hippocampal activity.

[1]  M. Frotscher,et al.  Axo‐axonic chandelier cells in the rat fascia dentata: Golgi‐electron microscopy and immunocytochemical studies , 1990, The Journal of comparative neurology.

[2]  R. S. Sloviter,et al.  A simplified timm stain procedure compatible with formaldehyde fixation and routine paraffin embedding of rat brain , 1982, Brain Research Bulletin.

[3]  J. Rogers,et al.  Calretinin and calbindin-D28k in rat brain: Patterns of partial co-localization , 1992, Neuroscience.

[4]  D. Prince,et al.  Inhibitory function in two models of chronic epileptogenesis , 1998, Epilepsy Research.

[5]  Floris G. Wouterlood.  Spotlight on the neurones (I): cell types, local connectivity, microcircuits, and distribution of markers , 2002 .

[6]  H. Katsumaru,et al.  GABAergic neurons containing the Ca2+-binding protein parvalbumin in the rat hippocampus and dentate gyrus , 1987, Brain Research.

[7]  G. Paxinos.  The Rat nervous system , 1985 .

[8]  M. Frotscher,et al.  “Dormant basket cell” hypothesis revisited: Relative vulnerabilities of dentate gyrus mossy cells and inhibitory interneurons after hippocampal status epilepticus in the rat , 2003, The Journal of comparative neurology.

[9]  R. S. Sloviter,et al.  Substance P receptor expression by inhibitory interneurons of the rat hippocampus: Enhanced detection using improved immunocytochemical methods for the preservation and colocalization of GABA and other neuronal markers , 2001, The Journal of comparative neurology.

[10]  A. Pitkänen,et al.  Distribution of calretinin‐immunoreactivity in the rat entorhinal cortex: Coexistence with GABA , 1997, The Journal of comparative neurology.

[11]  R. Miettinen,et al.  Characterization of Target Cells for Aberrant Mossy Fiber Collaterals in the Dentate Gyrus of Epileptic Rat , 1997, Experimental Neurology.

[12]  T. Freund,et al.  Delayed cell death in the contralateral hippocampus following kainate injection into the CA3 subfield , 1995, Neuroscience.

[13]  T. Babb,et al.  In contrast to kindled seizures, the frequency of spontaneous epilepsy in the limbic status model correlates with greater aberrant fascia dentata excitatory and inhibitory axon sprouting, and increased staining for N-methyl-d-aspartate, AMPA and GABAA receptors , 1997, Neuroscience.

[14]  R. Schwarcz,et al.  Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  T. Babb,et al.  Sprouting of GABAergic and mossy fiber axons in dentate gyrus following intrahippocampal kainate in the rat , 1990, Experimental Neurology.

[16]  A. Lörincz,et al.  Physiological patterns in the hippocampo‐entorhinal cortex system , 2000, Hippocampus.

[17]  Alterations of hippocampal GABAergic system contribute to development of spontaneous recurrent seizures in the rat lithium‐pilocarpine model of temporal lobe epilepsy , 2001, Hippocampus.

[18]  T. Babb,et al.  Synaptic reorganization by mossy fibers in human epileptic fascia dentata , 1991, Neuroscience.

[19]  Z. Borhegyi,et al.  Preservation of perisomatic inhibitory input of granule cells in the epileptic human dentate gyrus , 2001, Neuroscience.

[20]  D. Tauck,et al.  Evidence of functional mossy fiber sprouting in hippocampal formation of kainic acid-treated rats , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[21]  E. Aronica,et al.  Progression of spontaneous seizures after status epilepticus is associated with mossy fibre sprouting and extensive bilateral loss of hilar parvalbumin and somatostatin‐immunoreactive neurons , 2001, The European journal of neuroscience.

[22]  G. Cascino,et al.  Mossy fiber synaptic reorganization in the epileptic human temporal lobe , 1989, Annals of neurology.

[23]  Z. Borhegyi,et al.  Changes in the distribution and connectivity of interneurons in the epileptic human dentate gyrus , 2000, Neuroscience.

[24]  M. Celio,et al.  Calbindin D-28k and parvalbumin in the rat nervous system , 1990, Neuroscience.

[25]  C. Ribak,et al.  Axon terminals of GABAergic chandelier cells are lost at epileptic foci , 1985, Brain Research.

[26]  R. S. Sloviter,et al.  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 , 1991, Hippocampus.

[27]  D. Jacobowitz,et al.  Calretinin is present in non-pyramidal cells of the rat hippocampus—II. Co-existence with other calcium binding proteins and gaba , 1992, Neuroscience.

[28]  H. Scharfman,et al.  Chronic changes in synaptic responses of entorhinal and hippocampal neurons after amino-oxyacetic acid (AOAA)-induced entorhinal cortical neuron loss. , 1998, Journal of neurophysiology.

[29]  A. Ylinen,et al.  Pattern of neuronal death in the rat hippocampus after status epilepticus. Relationship to calcium binding protein content and ischemic vulnerability , 1992, Brain Research Bulletin.

[30]  J. Rogers,et al.  Calretinin in rat brain: An immunohistochemical study , 1992, Neuroscience.

[31]  T. Freund,et al.  Interneurons Containing Calretinin Are Specialized to Control Other Interneurons in the Rat Hippocampus , 1996, The Journal of Neuroscience.

[32]  N. Barbaro,et al.  Calcium‐binding protein (calbindin‐D28K) and parvalbumin immunocytochemistry in the normal and epileptic human hippocampus , 1991, The Journal of comparative neurology.

[33]  J. DeFelipe.  Chandelier cells and epilepsy. , 1999, Brain : a journal of neurology.

[34]  F. H. Lopes da Silva,et al.  Long‐lasting increased excitability differs in dentate gyrus vs. CA1 in freely moving chronic epileptic rats after electrically induced status epilepticus , 2002, Hippocampus.

[35]  H. Scharfman.  The parahippocampal region in temporal lobe epilepsy , 2002 .

[36]  N. Fountain,et al.  Responses of the superficial entorhinal cortex in vitro in slices from naive and chronically epileptic rats. , 1996, Journal of neurophysiology.

[37]  G. Danscher,et al.  Histochemical demonstration of heavy metals , 1981, Histochemistry.

[38]  H. Wheal,et al.  Changes in parvalbumin-immunoreactive neurons in the rat hippocampus following a kainic acid lesion , 1993, Neuroscience Letters.

[39]  G. Buzsáki,et al.  Interneurons of the hippocampus , 1998, Hippocampus.

[40]  Edward H Bertram,et al.  Self-sustaining limbic status epilepticus induced by ‘continuous’ hippocampal stimulation: electrographic and behavioral characteristics , 1989, Epilepsy Research.

[41]  Xiling Wen,et al.  Reduced Inhibition and Increased Output of Layer II Neurons in the Medial Entorhinal Cortex in a Model of Temporal Lobe Epilepsy , 2003, The Journal of Neuroscience.

[42]  D. Spencer,et al.  Entorhinal‐Hippocampal Interactions in Medial Temporal Lobe Epilepsy , 1994, Epilepsia.

[43]  Christian E. Elger,et al.  Preservation of Calretinin‐immunoreactive Neurons in the Hippocampus of Epilepsy Patients with Ammon's Horn Sclerosis , 1996, Journal of neuropathology and experimental neurology.

[44]  Eleonora Aronica,et al.  Neuronal Cell Death in a Rat Model for Mesial Temporal Lobe Epilepsy Is Induced by the Initial Status Epilepticus and Not by Later Repeated Spontaneous Seizures , 2003, Epilepsia.

[45]  R. S. Sloviter.  Calcium‐binding protein (calbindin‐D28k) and parvalbumin immunocytochemistry: Localization in the rat hippocampus with specific reference to the selective vulnerability of hippocampal neurons to seizure activity , 1989, The Journal of comparative neurology.

[46]  M. Avoli,et al.  Laminar organization of epileptiform discharges in the rat entorhinal cortex in vitro , 1998, The Journal of physiology.

[47]  T. Freund,et al.  Selective neuronal death in the contralateral hippocampus following unilateral kainate injections into the CA3 subfield , 1993, Neuroscience.

[48]  D. Jacobowitz,et al.  Calretinin is present in non-pyramidal cells of the rat hippocampus—I. A new type of neuron specifically associated with the mossy fibre system , 1992, Neuroscience.

[49]  O. P. Ottersen,et al.  Ultrastructure and immunocytochemical distribution of GABA in layer III of the rat medial entorhinal cortex following aminooxyacetic acid-induced seizures , 1999, Experimental Brain Research.

[50]  N. Fountain,et al.  Responses of deep entorhinal cortex are epileptiform in an electrogenic rat model of chronic temporal lobe epilepsy. , 1998, Journal of Neurophysiology.

[51]  A. Alonso,et al.  Muscarinic Induction of Synchronous Population Activity in the Entorhinal Cortex , 1997, The Journal of Neuroscience.

[52]  N. Spruston,et al.  Interneurons in the stratum lucidum of the rat hippocampus: An anatomical and electrophysiological characterization , 1997, The Journal of comparative neurology.

[53]  F. Dudek,et al.  Electrophysiology of dentate granule cells after kainate-induced synaptic reorganization of the mossy fibers , 1992, Brain Research.