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Science 15 November 2002:
Vol. 298. no. 5597, pp. 1418 - 1421
DOI: 10.1126/science.1076510
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Reports

On the Origin of Interictal Activity in Human Temporal Lobe Epilepsy in Vitro

Ivan Cohen,1 Vincent Navarro,24 Stéphane Clemenceau,13 Michel Baulac,12 Richard Miles1*

The origin and mechanisms of human interictal epileptic discharges remain unclear. Here, we describe a spontaneous, rhythmic activity initiated in the subiculum of slices from patients with temporal lobe epilepsy. Synchronous events were similar to interictal discharges of patient electroencephalograms. They were suppressed by antagonists of either glutamatergic or gamma -aminobutyric acid (GABA)-ergic signaling. The network of neurons discharging during population events comprises both subicular interneurons and a subgroup of pyramidal cells. In these pyramidal cells, GABAergic synaptic events reversed at depolarized potentials. Depolarizing GABAergic responses in neurons downstream to the sclerotic CA1 region contribute to human interictal activity.

1 EMI 0224, CHU Pitié-Salpêtrière, Université Paris VI, 75013 Paris, France.
2 Epilepsy Unit,
3 Department of Neurosurgery,
4 CNRS UPR640, Hôpital Pitié-Salpêtrière AP-HP, 75013, Paris, France.
*   To whom correspondence should be addressed. E-mail: rmiles{at}biomedicale.univ-paris5.fr.

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Neurosci. 25, 3601-3612
   Abstract »    Full Text »    PDF »
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Y. Fan, B. Zou, Y. Ruan, Z. Pang, and Z. C. Xu (2005)
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   Abstract »    Full Text »    PDF »
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E. Palma, G. Spinelli, G. Torchia, A. Martinez-Torres, D. Ragozzino, R. Miledi, and F. Eusebi (2005)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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C. Bernard, A. Anderson, A. Becker, N. P. Poolos, H. Beck, and D. Johnston (2004)
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   Abstract »    Full Text »    PDF »
Phosphatase inhibitors remove the run-down of {gamma}-aminobutyric acid type A receptors in the human epileptic brain.
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   Abstract »    Full Text »    PDF »
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J. Neurosci. 24, 5525-5536
   Abstract »    Full Text »    PDF »
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Y. Fujiwara-Tsukamoto, Y. Isomura, K. Kaneda, and M. Takada (2004)
J. Physiol. 557, 961-979
   Abstract »    Full Text »    PDF »
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Y. Zhu, R. L. Stornetta, and J. J. Zhu (2004)
J. Neurosci. 24, 5101-5108
   Abstract »    Full Text »    PDF »
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C. Rivera, J. Voipio, J. Thomas-Crusells, H. Li, Z. Emri, S. Sipila, J. A. Payne, L. Minichiello, M. Saarma, and K. Kaila (2004)
J. Neurosci. 24, 4683-4691
   Abstract »    Full Text »    PDF »
Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus.
J. I. Arellano, A. Munoz, I. Ballesteros-Yanez, R. G. Sola, and J. DeFelipe (2004)
Brain 127, 45-64
   Abstract »    Full Text »    PDF »
Glutamatergic Propagation of GABAergic Seizure-Like Afterdischarge in the Hippocampus In Vitro.
Y. Isomura, Y. Fujiwara-Tsukamoto, and M. Takada (2003)
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   Abstract »    Full Text »    PDF »
Synaptically Activated Cl- Accumulation Responsible for Depolarizing GABAergic Responses in Mature Hippocampal Neurons.
Y. Isomura, M. Sugimoto, Y. Fujiwara-Tsukamoto, S. Yamamoto-Muraki, J. Yamada, and A. Fukuda (2003)
J Neurophysiol 90, 2752-2756
   Abstract »    Full Text »    PDF »
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M. J. Wallace, R. E. Blair, K. W. Falenski, B. R. Martin, and R. J. DeLorenzo (2003)
J. Pharmacol. Exp. Ther. 307, 129-137
   Abstract »    Full Text »    PDF »
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C. Vale, J. Schoorlemmer, and D. H. Sanes (2003)
J. Neurosci. 23, 7516-7524
   Abstract »    Full Text »    PDF »
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Science 301, 463d
   Full Text »    PDF »
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J. Neurosci. 23, 5337-5341
   Abstract »    Full Text »    PDF »
Control of bursting by local inhibition in the rat subiculum in vitro.
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   Abstract »    Full Text »    PDF »
The Role of the Hyperpolarization-Activated Cationic Current Ih in the Timing of Interictal Bursts in the Neonatal Hippocampus.
A. Agmon and J. E. Wells (2003)
J. Neurosci. 23, 3658-3668
   Abstract »    Full Text »    PDF »


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