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      Disinhibition-induced transitions between absence and tonic-clonic epileptic seizures

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      1 , 1 , a , 2 , 3 , 4
      Scientific Reports
      Nature Publishing Group

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          Abstract

          Electrophysiological experiments have long revealed the existence of two-way transitions between absence and tonic-clonic epileptic seizures in the cerebral cortex. Based on a modified spatially-extended Taylor & Baier neural field model, we here propose a computational framework to mathematically describe the transition dynamics between these epileptic seizures. We first demonstrate the existence of various transition types that are induced by disinhibitory functions between two inhibitory variables in an isolated Taylor & Baier model. Moreover, we show that these disinhibition-induced transitions can lead to stable tonic-clonic oscillations as well as periodic spike with slow-wave discharges, which are the hallmark of absence seizures. We also observe fascinating dynamical states, such as periodic 2-spike with slow-wave discharges, tonic death, bursting oscillations, as well as saturated firing. Most importantly, we identify paths that represent physiologically plausible transitions between absence and tonic-clonic seizures in the modified spatially-extended Taylor & Baier model.

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          Most cited references33

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          Cortical interneurons that specialize in disinhibitory control

          In the mammalian cerebral cortex, the diversity of interneuronal subtypes underlies a division of labor subserving distinct modes of inhibitory control 1–7 . A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation 8,9 . Although several interneuron populations are known to target other interneurons to varying degrees 10–15 , little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells, respectively 3,6,16,17 . During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in auditory cortex, and in turn VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell-type and microcircuit underlying disinhibitory control in cortex and demonstrate that it is activated under specific behavioural conditions.
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            Dynamics of pattern formation in lateral-inhibition type neural fields.

            S Amari (1977)
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              On the cellular and network bases of epileptic seizures.

              The highly interconnected networks of the mammalian forebrain can generate a wide variety of synchronized activities, including those underlying epileptic seizures, which often appear as a transformation of otherwise normal brain rhythms. The cerebral cortex and hippocampus are particularly prone to the generation of the large, synchronized bursts of activity underlying many forms of seizures owing to strong recurrent excitatory connections, the presence of intrinsically burst-generating neurons, ephaptic interactions among closely spaced neurons, and synaptic plasticity. The simplest form of epileptiform activity in these structures is the interictal spike, a synchronized burst of action potentials generated by recurrent excitation, followed by a period of hyperpolarization, in a localized pool of pyramidal neurons. Seizures can also be generated in response to a loss of balance between excitatory and inhibitory influences and can take the form of either tonic depolarizations or repetitive, rhythmic burst discharges, either as clonic or spike-wave activity, again mediated both by intrinsic membrane properties and synaptic interactions. The interaction of the cerebral cortex and the thalamus, in conjunction with intrathalamic communication, can also generate spike waves similar to those occurring during human absence seizure discharges. Although epileptic syndromes and their causes are diverse, the cellular mechanisms of seizure generation appear to fall into only two categories: rhythmic or tonic "runaway" excitation or the synchronized and rhythmic interplay between excitatory and inhibitory neurons and membrane conductances.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                30 July 2015
                2015
                : 5
                : 12618
                Affiliations
                [1 ]Department of Dynamics and Control, Beihang University , Beijing 100191, China
                [2 ]Department of Physics, Faculty of Science, King Abdulaziz University , Jeddah, Saudi Arabia
                [3 ]Faculty of Natural Sciences and Mathematics, University of Maribor , Koroška cesta 160, SI-2000 Maribor, Slovenia
                [4 ]CAMTP—Center for Applied Mathematics and Theoretical Physics, University of Maribor , Krekova 2, SI-2000 Maribor, Slovenia
                Author notes
                Article
                srep12618
                10.1038/srep12618
                4519733
                26224066
                269879cc-7f23-4b7b-b805-73d793ad9272
                Copyright © 2015, Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 27 February 2015
                : 02 July 2015
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