Brain Advance Access originally published online on June 2, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Brain, Vol. 127, No. 7, 1626-1640,
July 2004
© 2004 Guarantors of Brain
doi: 10.1093/brain/awh181
GABAA receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex
1 Dipartimento di Fisiologia Umana e Farmacologia ‘V. Erspamer’, Università degli Studi di Roma ‘La Sapienza’, Roma, 2 IRCCS Neuromed, Pozzilli (Is) and 3 IRCCS Fondazione Santa Lucia, Roma, Italy, 4 INSERM U 109, Centre de Recherche P. Broca and Hôpital Sainte-Anne, Paris, France, 5 Department of Epileptology, University of Bonn, Bonn, Germany and 6 Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, Montréal, Québec, Canada
Correspondence to: M. Avoli, MD, PhD, 3801 University Street, Montreal, QC, H3A 2B4 Canada E-mail: massimo.avoli{at}mcgill.ca
Patients with Taylor’s type focal cortical dysplasia (FCD) present with seizures that are often medically intractable. Here, we attempted to identify the cellular and pharmacological mechanisms responsible for this epileptogenic state by using field potential and K+-selective recordings in neocortical slices obtained from epileptic patients with FCD and, for purposes of comparison, with mesial temporal lobe epilepsy (MTLE), an epileptic disorder that, at least in the neocortex, is not characterized by any obvious structural aberration of neuronal networks. Spontaneous epileptiform activity was induced in vitro by applying 4-aminopyridine (4AP)-containing medium. Under these conditions, we could identify in FCD slices a close temporal relationship between ictal activity onset and the occurrence of slow interictal-like events that were mainly contributed by GABAA receptor activation. We also found that in FCD slices, pharmacological procedures capable of decreasing or increasing GABAA receptor function abolished or potentiated ictal discharges, respectively. In addition, the initiation of ictal events in FCD tissue coincided with the occurrence of GABAA receptor-dependent interictal events leading to [K+]o elevations that were larger than those seen during the interictal period. Finally, by testing the effects induced by baclofen on epileptiform events generated by FCD and MTLE slices, we discovered that the function of GABAB receptors (presumably located at presynaptic inhibitory terminals) was markedly decreased in FCD tissue. Thus, epileptiform synchronization leading to in vitro ictal activity in the human FCD tissue is initiated by a synchronizing mechanism that paradoxically relies on GABAA receptor activation causing sizeable increases in [K+]o. This mechanism may be facilitated by the decreased ability of GABAB receptors to control GABA release from interneuron terminals.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  F.-W. Zhou, H.-X. Chen, and S. N. Roper Balance of Inhibitory and Excitatory Synaptic Activity Is Altered in Fast-Spiking Interneurons in Experimental Cortical Dysplasia J Neurophysiol, October 1, 2009; 102(4): 2514 - 2525. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ben-Ari, J.-L. Gaiarsa, R. Tyzio, and R. Khazipov GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations Physiol Rev, October 1, 2007; 87(4): 1215 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wu, Y. Chang, G. Li, F. Xue, J. DeChon, K. Ellsworth, Q. Liu, K. Yang, N. Bahadroani, C. Zheng, et al. Electrophysiological Properties and Subunit Composition of GABAA Receptors in Patients With Gelastic Seizures and Hypothalamic Hamartoma J Neurophysiol, July 1, 2007; 98(1): 5 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Laschet, I. Kurcewicz, F. Minier, S. Trottier, J. Khallou-Laschet, J. Louvel, S. Gigout, B. Turak, A. Biraben, J.-M. Scarabin, et al. Dysfunction of GABAA receptor glycolysis-dependent modulation in human partial epilepsy PNAS, February 27, 2007; 104(9): 3472 - 3477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Zsiros, I. Aradi, and G. Maccaferri Propagation of postsynaptic currents and potentials via gap junctions in GABAergic networks of the rat hippocampus J. Physiol., January 15, 2007; 578(2): 527 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Klaassen, J. Glykys, J. Maguire, C. Labarca, I. Mody, and J. Boulter Seizures and enhanced cortical GABAergic inhibition in two mouse models of human autosomal dominant nocturnal frontal lobe epilepsy PNAS, December 12, 2006; 103(50): 19152 - 19157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Xiang, H.-X. Chen, X.-X. Yu, M. A. King, and S. N. Roper Reduced Excitatory Drive in Interneurons in an Animal Model of Cortical Dysplasia J Neurophysiol, August 1, 2006; 96(2): 569 - 578. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Calcagnotto, M. F. Paredes, T. Tihan, N. M. Barbaro, and S. C. Baraban Dysfunction of Synaptic Inhibition in Epilepsy Associated with Focal Cortical Dysplasia J. Neurosci., October 19, 2005; 25(42): 9649 - 9657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bernasconi, D. Kinay, F. Andermann, S. Antel, and A. Bernasconi Analysis of shape and positioning of the hippocampal formation: an MRI study in patients with partial epilepsy and healthy controls Brain, October 1, 2005; 128(10): 2442 - 2452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Kantrowitz, N. N. Francis, A. Salah, and K. L. Perkins Synaptic Depolarizing GABA Response in Adults Is Excitatory and Proconvulsive When GABAB Receptors Are Blocked J Neurophysiol, May 1, 2005; 93(5): 2656 - 2667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Manikandan, P. K. Sinha, P. K. Neema, and R. C. Rathod Severe Seizures During Propofol Induction in a Patient with Syringomyelia Receiving Baclofen Anesth. Analg., May 1, 2005; 100(5): 1468 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Jacobs and D. A. Prince Excitatory and Inhibitory Postsynaptic Currents in a Rat Model of Epileptogenic Microgyria J Neurophysiol, February 1, 2005; 93(2): 687 - 696. [Abstract] [Full Text] [PDF]
|
|