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Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy

Abstract

Impaired inhibition is thought to be important in temporal lobe epilepsy (TLE), the most common form of epilepsy in adult patients. We report that, in experimental TLE, spontaneous GABAergic inhibition was increased in the soma but reduced in the dendrites of pyramidal neurons. The former resulted from the hyperactivity of somatic projecting interneurons, whereas the latter was probably due to the degeneration of a subpopulation of dendritic projecting interneurons. A deficit in dendritic inhibition could reduce seizure threshold, whereas enhanced somatic inhibition would prevent the continuous occurrence of epileptiform activity.

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Figure 1: GAD67-, somatostatin- and calbindin-containing neurons in the CA1 region of the hippocampal formation in control (a, c, e, g) and pilocarpine-treated (b, d, f, h, i, j) rats.
Figure 2: Density of asymmetrical and symmetrical synapses in stratum lacunosum moleculare.
Figure 3: Stratum radiatum and stratum pyramidale interneurons are hyperactive in TLE.
Figure 4: Recordings from basket cells in control and epileptic rats.
Figure 5: Recordings from stratum oriens interneurons in control and epileptic rats.
Figure 6: Recordings from the apical dendrites of CA1 pyramidal cells.
Figure 7: Somatic recordings from CA1 pyramidal cells.
Figure 8: Functional consequences of the decrease of dendritic inhibition.

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Acknowledgements

We thank A.J. Tobin and N.J.K. Tillakaratne for the GAD67 cDNA and D. Diabira for the kainate-lesioned animals. This work was supported by I.N.S.E.R.M and the Simone and Cino del Duca Foundation.

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Correspondence to Y. Ben-Ari.

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Cossart, R., Dinocourt, C., Hirsch, J. et al. Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy. Nat Neurosci 4, 52–62 (2001). https://doi.org/10.1038/82900

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