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.
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Acknowledgements
This article is dedicated to Philip A. Schwartzkroin, a pioneer and leader in epilepsy research, esteemed mentor, and outstanding colleague.
Other Acknowledgements
Supported by R01 NS-081203, R21 MH-090606 and the New York State Office of Mental Health (HES) and R01 NS-038595, R01 NS-051710, R01-NS-050393 and grants from Citizens United for Research in Epilepsy, Department of Defense and the American Epilepsy Society (ABK).
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Scharfman, H.E., Brooks-Kayal, A.R. (2014). Is Plasticity of GABAergic Mechanisms Relevant to Epileptogenesis?. In: Scharfman, H., Buckmaster, P. (eds) Issues in Clinical Epileptology: A View from the Bench. Advances in Experimental Medicine and Biology, vol 813. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-8914-1_11
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