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Are Changes in Synaptic Function That Underlie Hyperexcitability Responsible for Seizure Activity?

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Issues in Clinical Epileptology: A View from the Bench

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 813))

Abstract

The synaptic and intrinsic mechanisms responsible for epileptic seizures and briefer interictal epileptic discharges have been characterized in some detail. This chapter will outline some aspects of this work in the context of focal epilepsies, particularly in the temporal lobe, and will identify some of the major questions that remain. Early work, mainly using the actions of convulsant treatments on brain slices in vitro, revealed synaptic circuitry that could recruit populations of neurons into synchronous epileptic discharges. Subsequent investigations into cellular mechanisms of chronic experimental and clinical foci, again often in vitro, have revealed complex changes in synaptic properties, synaptic connectivity, intrinsic neuronal properties and selective losses of neurons: unraveling their roles in generating seizures, interictal discharges and interictal dysfunctions/comorbidities remains a significant challenge. In vivo recordings have revealed aspects of the pathophysiology of epileptic foci that have practical implications, for instance high-frequency oscillations, and potentially high-frequency hypersynchronous neuronal firing, which have been useful in localizing the epileptogenic zone for surgical resection.

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Acknowledgements

I am grateful for research support from Epilepsy Research UK (P1102) and the Medical Research Council of the UK (G082162).

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  1. Departments of Pharmacology and Biochemistry, University of Oxford, Oxford, OX1 3QT, UK

    John G. R. Jefferys

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  1. Dept. of Child & Adoles. Psych., Phys. & Neurosc., and Psych., New York Univ. Langone Med. Ctr., Orangeburg, New York, USA

    Helen E. Scharfman

  2. Dept. of Comp. Med. and Neurol. & Neurol. Scs., Stanford University, Stanford, California, USA

    Paul S. Buckmaster

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Jefferys, J.G.R. (2014). Are Changes in Synaptic Function That Underlie Hyperexcitability Responsible for Seizure Activity?. 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_15

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