QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 19, 2005, 25(42):9649-9657; doi:10.1523/JNEUROSCI.2687-05.2005

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Calcagnotto, M. E. Articles by Baraban, S. C. Search for Related Content PubMed PubMed Citation Articles by Calcagnotto, M. E. Articles by Baraban, S. C.

 Previous Article  |  Next Article 

Neurobiology of Disease
Dysfunction of Synaptic Inhibition in Epilepsy Associated with Focal Cortical Dysplasia

Maria Elisa Calcagnotto,¹ Mercedes F. Paredes,^1,2 Tarik Tihan,³ Nicholas M. Barbaro,¹ and Scott C. Baraban^1,2

¹Epilepsy Research Laboratory, Department of Neurological Surgery, ²Graduate Program in Neuroscience, and ³Department of Pathology, University of California, San Francisco, San Francisco, California 94143

Focal cortical dysplasia (FCD) is a common and important cause of medically intractable epilepsy. In patients with temporal lobe epilepsy and in several animal models, compromised neuronal inhibition, mediated by GABA, contributes to seizure genesis. Although reduction in GABAergic interneuron density has been reported in FCD tissue samples, there is little available information on the resulting physiological changes in synaptic inhibition and the potential contribution of these changes to epileptogenesis in the dysplastic human brain. Using visualized whole-cell patch-clamp recordings from identified neurons in tissue slices obtained from patients with FCD, we demonstrate that GABA_A-receptor-mediated inhibition is substantially altered in regions of dysplasia. These alterations include a significant reduction in IPSC frequency and a potentially compensatory decrease in transporter-mediated GABA reuptake function; the latter is marked by a significant increase in the decay-time constant for evoked and spontaneous IPSCs and a lack of effect of the GABA transport-inhibitor 1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride on IPSC kinetics. Immunohistochemical staining revealed a scattering of GABAergic interneurons across dysplastic cortex and striking reductions in GABA transporter expression. Together, these results suggest that profound alterations in GABA-mediated synaptic inhibition play an essential role in the process of epileptogenesis in patients with FCD.

Key words: dysplasia; epilepsy; human brain slices; inhibition; GABA; GAT

---

Received June 29, 2005; revised August 19, 2005; accepted September 3, 2005.

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]

				R.-Z. Zhan and J. V. Nadler Enhanced Tonic GABA Current in Normotopic and Hilar Ectopic Dentate Granule Cells After Pilocarpine-Induced Status Epilepticus J Neurophysiol, August 1, 2009; 102(2): 670 - 681. [Abstract] [Full Text] [PDF]

				J. B. Ackman, L. Aniksztejn, V. Crepel, H. Becq, C. Pellegrino, C. Cardoso, Y. Ben-Ari, and A. Represa Abnormal Network Activity in a Targeted Genetic Model of Human Double Cortex J. Neurosci., January 14, 2009; 29(2): 313 - 327. [Abstract] [Full Text] [PDF]

				D. L. Jones and S. C. Baraban Characterization of Inhibitory Circuits in the Malformed Hippocampus of Lis1 Mutant Mice J Neurophysiol, November 1, 2007; 98(5): 2737 - 2746. [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]

				P. Lamparello, M. Baybis, J. Pollard, E. M. Hol, D. D. Eisenstat, E. Aronica, and P. B. Crino Developmental lineage of cell types in cortical dysplasia with balloon cells Brain, September 1, 2007; 130(9): 2267 - 2276. [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]

				S. A. Trotter, J. Kapur, M. J. Anzivino, and K. S. Lee GABAergic Synaptic Inhibition Is Reduced before Seizure Onset in a Genetic Model of Cortical Malformation. J. Neurosci., October 18, 2006; 26(42): 10756 - 10767. [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]

				J. Epsztein, M. Milh, R. Id Bihi, I. Jorquera, Y. Ben-Ari, A. Represa, and V. Crepel Ongoing epileptiform activity in the post-ischemic hippocampus is associated with a permanent shift of the excitatory-inhibitory synaptic balance in CA3 pyramidal neurons. J. Neurosci., June 28, 2006; 26(26): 7082 - 7092. [Abstract] [Full Text] [PDF]

				E. Palma, M. Amici, F. Sobrero, G. Spinelli, S. Di Angelantonio, D. Ragozzino, A. Mascia, C. Scoppetta, V. Esposito, R. Miledi, et al. Anomalous levels of Cl- transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory PNAS, May 30, 2006; 103(22): 8465 - 8468. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help