A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy
A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy
Post mortem studies on the hippocampi of human epileptics have shown altered anatomy and remodelling of the circuitry in the dentate gyrus, which is also found in many of the animal models of TLE. Electrophysiological studies in these models have produced conflicting data on the excitability and inhibition of granule cells in the dentate gyrus. The unilateral injection of the excitotoxin kainic acid into the lateral ventricle of the rat causes a lesion similar to endfolium sclerosis seen in humans and induces epileptiform activity in the hippocampus. I have performed electrophysiological studies in this model to assess the excitatory and inhibitory influences on granule cells at various times after the injection of kainic acid. I have also used immunocytochemical and in situ hybridization techniques in order to investigate changes in the numbers of inhibitory and modulatory interneurons in the dentate gyrus following kainic acid. I have shown an increase in granule cell excitability up to 12 weeks after injection demonstrated by increased population responses and a left shift in the E/S relationship. Further, there is a progressive and permanent reduction in granule cell feedforward inhibition initiated by commissural stimulation, but no change in feedback inhibition. Long latency inhibition and granule cell plasticity in the form of long term potentiation and depression were unaffected. I have also shown that there is no change in the numbers of somatostatin and neuropeptide-Y (NPY) immunoreactive interneurons in the dentate gyrus, indicating that changes in the population of these cells are not responsible for the functional changes seen; however a novel expression of NPY was seen in granule cells in kainic acid treated animals.
University of Southampton
1997
Barrow, Paul Anthony
(1997)
A study of the changes in dentate granule cell excitability and inhibition in the kainic acid model of temporal lobe epilepsy.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Post mortem studies on the hippocampi of human epileptics have shown altered anatomy and remodelling of the circuitry in the dentate gyrus, which is also found in many of the animal models of TLE. Electrophysiological studies in these models have produced conflicting data on the excitability and inhibition of granule cells in the dentate gyrus. The unilateral injection of the excitotoxin kainic acid into the lateral ventricle of the rat causes a lesion similar to endfolium sclerosis seen in humans and induces epileptiform activity in the hippocampus. I have performed electrophysiological studies in this model to assess the excitatory and inhibitory influences on granule cells at various times after the injection of kainic acid. I have also used immunocytochemical and in situ hybridization techniques in order to investigate changes in the numbers of inhibitory and modulatory interneurons in the dentate gyrus following kainic acid. I have shown an increase in granule cell excitability up to 12 weeks after injection demonstrated by increased population responses and a left shift in the E/S relationship. Further, there is a progressive and permanent reduction in granule cell feedforward inhibition initiated by commissural stimulation, but no change in feedback inhibition. Long latency inhibition and granule cell plasticity in the form of long term potentiation and depression were unaffected. I have also shown that there is no change in the numbers of somatostatin and neuropeptide-Y (NPY) immunoreactive interneurons in the dentate gyrus, indicating that changes in the population of these cells are not responsible for the functional changes seen; however a novel expression of NPY was seen in granule cells in kainic acid treated animals.
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Published date: 1997
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Local EPrints ID: 460269
URI: http://eprints.soton.ac.uk/id/eprint/460269
PURE UUID: cda13d9d-02b6-4a1c-9cf9-20ebb20671d6
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Date deposited: 04 Jul 2022 18:17
Last modified: 04 Jul 2022 18:17
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Author:
Paul Anthony Barrow
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