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Issues in Clinical Epileptology: A View from the Bench

Volume 813 of the series Advances in Experimental Medicine and Biology pp 133-150

Date:

Is Plasticity of GABAergic Mechanisms Relevant to Epileptogenesis?

  • Helen E. ScharfmanAffiliated withThe Nathan S. Kline Institute for Psychiatric ResearchDepartments of Child & Adolescent Psychiatry, Physiology & Neuroscience, and Psychiatry, New York University Langone Medical Center Email author 
  • , Amy R. Brooks-KayalAffiliated withDepartments of Pediatrics, Neurology and Pharmaceutical Sciences, University of Colorado School of MedicineSkaggs School of Pharmacy and Pharmaceutical SciencesChildren’s Hospital Colorado

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Abstract

Numerous changes in GABAergic neurons, receptors, and inhibitory mechanisms have been described in temporal lobe epilepsy (TLE), either in humans or in animal models. Nevertheless, there remains a common assumption that epilepsy can be explained by simply an insufficiency of GABAergic inhibition. Alternatively, investigators have suggested that there is hyperinhibition that masks an underlying hyperexcitability. Here we examine the status epilepticus (SE) models of TLE and focus on the dentate gyrus of the hippocampus, where a great deal of data have been collected. The types of GABAergic neurons and GABAA receptors are summarized under normal conditions and after SE. The role of GABA in development and in adult neurogenesis is discussed. We suggest that instead of “too little or too much” GABA there is a complexity of changes after SE that makes the emergence of chronic seizures (epileptogenesis) difficult to understand mechanistically, and difficult to treat. We also suggest that this complexity arises, at least in part, because of the remarkable plasticity of GABAergic neurons and GABAA receptors in response to insult or injury.

Keywords

GABA GABAA receptor Interneuron α1 subunit Chloride channel Granule cell Adult neurogenesis Status epilepticus Febrile seizures Aberrant neurogenesis Ectopic granule cell