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How Is Homeostatic Plasticity Important in Epilepsy?

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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

Maintaining physiological variables within narrow operating limits by homeostatic mechanisms is a fundamental property of most if not all living cells and organisms. In recent years, research from many laboratories has shown that the activity of neurons and neural circuits are also homeostatically regulated. Here, we attempt to apply concepts of homeostasis in general, and more specifically synaptic homeostatic plasticity, to the study of epilepsy. We hypothesize that homeostatic mechanisms are actively engaged in the epileptic brain. These processes attempt to re-establish normal neuronal and network activity, but are opposed by the concurrent mechanisms underlying epileptogenesis. In forms of intractable epilepsy, seizures are so frequent and intense that homeostatic mechanisms are unable to restore normal levels of neuronal activity. In such cases, we contend that homeostatic plasticity mechanisms nevertheless remain active. However, their continuing attempts to reset neuronal activity become maladaptive and results in dyshomeostasis with neurobehavioral consequences. Using the developing hippocampus as a model system, we briefly review experimental results and present a series of arguments to propose that the cognitive neurobehavioral comorbidities of childhood epilepsy result, at least in part, from unchecked homeostatic mechanisms.

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Acknowledgement

From John Swann: I remember first meeting you at the 1981 SfN Meeting. At that point, I had inadvertently stumbled into epilepsy research but became intrigued by how little was known about the basic mechanisms of the childhood epilepsies. You had recently published your first papers on epileptiform activity in immature hippocampal slices and I was in the midst of somewhat similar experiments as a newly minted independent investigator. During our conversation, you encouraged me to continue my line of investigation even though we were potential competitors. Your generous gesture contributed importantly to my commitment to epilepsy research and I have valued you as a friend and colleague throughout the intervening years. I think this book in many ways reflects the positive influence you have had on the careers of so many scientists – in epilepsy and the neurosciences more generally. This is a legacy to be proud of and emulated by your students and the future generations of their students.

From Jong Rho: We first met while I was interviewing for my first faculty position at the University of Washington and the Seattle Children’s Hospital in 1994. Your remarkable presence and the opportunity to launch an independent research career under your guidance were critical factors in my decision to relocate there after my post-doctoral training at the NIH. Without your constant support and mentorship, I would not have been able to secure my first research grant through the Epilepsy Foundation of America and a career development award from the NIH. The high point of my tenure in Seattle was working with you in creating the Pediatric Epilepsy Research Center, and to jointly delve into the mechanisms of ketogenic diet action in epileptic brain – an interest that has remained to this day. You have always been a role model for me, and have continued to exemplify the highest standards of scientific integrity, intellectual rigor, selflessness and humility, and most important of all, the humanity and love of those with whom you worked. This volume is a testament to all of that and more.

Other acknowledgement

Work in the Swann Lab has been supported by grants from NIH-NINDS and CURE, and in the Rho Lab by grants from NIH-NINDS and Canadian Institutes for Health Research.

Author information

Authors and Affiliations

  1. The Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Baylor College of Medicine, 1250 Moursund St, Houston, TX, 77030, USA

    John W. Swann

  2. Departments of Pediatrics and Clinical Neurosciences, Alberta Children’s Hospital, Calgary, AB, Canada

    Jong M. Rho

  3. Faculty of Medicine, University of Calgary, Calgary, AB, Canada

    Jong M. Rho

Authors
  1. John W. Swann
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Correspondence to John W. Swann .

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Editors and Affiliations

  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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Swann, J.W., Rho, J.M. (2014). How Is Homeostatic Plasticity Important in Epilepsy?. 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_10

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  • DOI: https://doi.org/10.1007/978-94-017-8914-1_10

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  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-017-8913-4

  • Online ISBN: 978-94-017-8914-1

  • eBook Packages: MedicineMedicine (R0)

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