Biochemical and morphological changes in the rat hippocampus following transection of the fimbria-fornix

According to electrophysiological studies, the subcortically denervated hippocampus has been suggested as a model for limbic epilepsy. We investigated a) whether fimbrial lesioning leads to any biochemical or morphological changes in the rat hippocampus, b) if these changes give any explanation to the previously indicated hyperexcitability, and c) if the changes are in line with the findings in other experimental models and human epilepsy. The fimbria-fornix transection was done by aspiration. Four months later, spontaneous EEG activities were recorded, and the hippocampal formation was processed for histology. In addition, a separate group of lesioned rats was used for hippocampal amino acid analysis. Hyperexcitable functioning of the hippocampus was seen as frequent and rhythmic spiking activity in 25% of the fimbria-fornix-lesioned rats, although the rest of them had spikes occasionally. The amino acids analysis revealed a notable decrease in the concentration of GABA but no significant changes in the amount of excitatory amino acids. This suggests impaired GABAergic functioning but does not exclude possible abnormalities in the release of both excitatory and inhibitory amino acids. The number of somatostatin-immunoreactive (SOM-IR) neurons, a subpopulation of GABAergic neurons, was decreased in all the areas of the hippocampus (CA3 > CA1 > hilus), but this was statistically significant only in the CA3 area. Interestingly, it is the region from which interictal spiking activity in the subcortically denervated rat presumable originates. Immunostaining for synaptophysin showed a dense band of granules in the inner molecular layer of the dentate gyrus, indicating probable synaptic reorganization of associational afferents.

[1]  T. Halonen,et al.  Effects of Vigabatrin (γ‐vinyl GAB A) on Neuro transmission‐Related Amino Acids and on GAB A nd Benzodiazepine Receptor Binding in Rats , 1991 .

[2]  R. Bakay,et al.  A decrease in the number of GABAergic somata is associated with the preferential loss of GABAergic terminals at epileptic foci , 1986, Brain Research.

[3]  Y. Ben-Ari,et al.  Hippocampal plasticity in childhood epilepsy , 1989, Neuroscience Letters.

[4]  G. Buzsáki,et al.  Emergence and propagation of interictal spikes in the subcortically denervated hippocampus , 1991, Hippocampus.

[5]  G. Lynch,et al.  Terminal proliferation and synaptogenesis following partial deafferentation: The reinnervation of the inner molecular layer of the dentate gyrus following removal of its commissural afferents , 1978, The Journal of comparative neurology.

[6]  G. Buzsáki.  Two-stage model of memory trace formation: A role for “noisy” brain states , 1989, Neuroscience.

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

[8]  J. Cavazos,et al.  Synaptic reorganization in the hippocampus induced by abnormal functional activity. , 1988, Science.

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

[10]  P. Greengard,et al.  Protein p38: an integral membrane protein specific for small vesicles of neurons and neuroendocrine cells , 1986, The Journal of cell biology.

[11]  D. Price,et al.  A modified histochemical technique to visualize acetylcholinesterase-containing axons. , 1985, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[12]  G. M. Peterson,et al.  Intragranular mossy fibers in rats and gerbils from synapses with the somata and proximal dendrites of basket cells in the dentate gyrus , 1991, Hippocampus.

[13]  A. Dravid,et al.  Noradrenergic, serotonergic, and cholinergic sprouting in the hippocampus that follows partial or complete transection of the septohippocampal pathway: Contributions of spared inputs , 1987, Experimental Neurology.

[14]  G. Sperk,et al.  Neuropeptide Y biosynthesis is markedly induced in mossy fibers during temporal lobe epilepsy of the rat , 1990, Neuroscience Letters.

[15]  Fred H. Gage,et al.  Reinnervation of the partially deafferented hippocampus by compensatory collateral sprouting from spared cholinergic and noradrenergic afferents , 1983, Brain Research.

[16]  G. Buzsáki.  Feed-forward inhibition in the hippocampal formation , 1984, Progress in Neurobiology.

[17]  H. Scharfman,et al.  Selective depression of GABA-mediated IPSPs by somatostatin in area CA1 of rabbit hippocampal slices , 1989, Brain Research.

[18]  James N. Davis,et al.  Sympathetic noradrenergic sprouting in response to central cholinergic denervation: A histochemical study of neuronal sprouting in the rat hippocampal formation , 1981, Brain Research.

[19]  Y. Ben-Ari,et al.  Limbic seizure and brain damage produced by kainic acid: Mechanisms and relevance to human temporal lobe epilepsy , 1985, Neuroscience.

[20]  C. Ribak,et al.  Direct commissural connections to the basket cells of the hippocampal dentate gyrus: anatomical evidence for feed-forward inhibition , 1984, Journal of neurocytology.

[21]  G. Buzsáki,et al.  Neuronal activity in the subcortically denervated hippocampus: A chronic model for epilepsy , 1989, Neuroscience.

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

[23]  David A. Drachman,et al.  Synaptic loss in Alzheimer's disease and other dementias , 1989, Neurology.

[24]  R. S. Sloviter.  Possible functional consequences of synaptic reorganization in the dentate gyrus of kainate-treated rats , 1992, Neuroscience Letters.

[25]  Y. Ben-Ari,et al.  Hippocampal plasticity in the kindling model of epilepsy in rats , 1989, Neuroscience Letters.

[26]  R. S. Sloviter.  “Epileptic” brain damage in rats induced by sustained electrical stimulation of the perforant path. I. Acute electrophysiological and light microscopic studies , 1983, Brain Research Bulletin.

[27]  F. Dudek,et al.  Chronic seizures and collateral sprouting of dentate mossy fibers after kainic acid treatment in rats , 1988, Brain Research.

[28]  T. Babb,et al.  Recovery of decreased glutamate decarboxylase immunoreactivity after rat hippocampal kindling , 1989, Epilepsy Research.

[29]  C. Léránth,et al.  Synaptic connections of neuropeptide Y (NPY) immunoreactive neurons in the hilar area of the rat hippocampus , 1990, The Journal of comparative neurology.

[30]  Y. Ben-Ari,et al.  Brief seizure episodes induce long-term potentiation and mossy fibre sprouting in the hippocampus , 1990, Trends in Neurosciences.

[31]  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.

[32]  D. Spencer,et al.  A selective loss of somatostatin in the hippocampus of patients with temporal lobe epilepsy , 1991, Annals of neurology.

[33]  D. Prince,et al.  Cellular and field potential properties of epileptogenic hippocampal slices , 1978, Brain Research.

[34]  B. Stanfield.  Excessive intra- and supragranular mossy fibers in the dentate gyrus of tottering (tg/tg) mice , 1989, Brain Research.

[35]  D. Spencer,et al.  Neurotransmitter markers in human seizure foci , 1991 .

[36]  R. C. Collins,et al.  Excitotoxic mechanisms of epileptic brain damage. , 1986, Advances in neurology.

[37]  A. Ylinen,et al.  Behavioural, electrophysiological and histopathological changes following sustained stimulation of the perforant pathway input to the hippocampus: Effect of the NMDA receptor antagonist, CGP 39551 , 1991, Brain Research.

[38]  V. Chan‐Palay,et al.  Somatostatin-like immunoreactive neurons in the hippocampus: An immunocytochemical study in the rat , 1982, Neuroscience Letters.

[39]  M. Leach,et al.  Changes in cortical amino acids during electrical kindling in rats , 1985, Neuropharmacology.

[40]  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.

[41]  R. S. Sloviter,et al.  Immunocytochemical localization of GABA‐, cholecystokinin‐, vasoactive intestinal polypeptide‐, and somatostatin‐like immunoreactivity in the area dentata and hippocampus of the rat , 1987, The Journal of comparative neurology.

[42]  G. Chejfec,et al.  Tissue fixation methods alter the immunohistochemical demonstrability of synaptophysin. , 1988, Ultrastructural pathology.

[43]  J. Pretorius,et al.  Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[44]  M. Frotscher,et al.  Afferent and efferent synaptic conncetions sof somatostatin‐immunoreactive neurons in the rat fascia dentata , 1990, The Journal of comparative neurology.

[45]  Bertram Wiedenmann,et al.  Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles , 1985, Cell.