Astrocytes and epilepsy

Abstract

Event Abstract Back to Event Astrocytes and epilepsy Giorgio Carmignoto1* 1 National Reserch Council (CNR), Institute of Neuroscience and University of Padova, Italy Epilepsy is a brain disorder characterized by unpredictable episodes of uncontrolled seizures. At a cellular level, seizure-like ictal events manifest as synchronous, intense firing discharges involving large populations of neurons. Our knowledge of the mechanisms underlying the initiation, the propagation and the cessation of focal seizures is, however, unsatisfactory. Using an experimental model of focal epilepsy in enthorinal or temporal cortex slice preparations, we recently revealed a contribution of astrocytes to the generation of focal ictal discharges. We found that in a cortical neuronal network prone to seizures due to slice perfusion with 4-aminopyridine and low Mg2+, an episode of neuronal hyperactivity triggered by local NMDA applications, evoked metabotropic glutamate receptor-mediated Ca2+ elevations in astrocytes which lowered seizure threshold. At the basis of this astrocyte action is probably the release of glutamate which enhances synchronous activities in pyramidal neurons. Because focal ictal discharge propagation is governed by a feed-forward inhibition mainly generated by parvalbumim fast-spiking (Pv-FS) interneurons (Trevelyan et al., 2006, 2007; Cammarota et al. 2013), we advance the hypothesis that this action of GABAergic interneurons can be also affected by astrocyte signaling. In favour of this hypothesis, a large number of astrocytes from both the enthorinal and temporal cortex were found to respond to local GABA applications with repetitive GABAB-mediated Ca2+ elevations. Activation of individual Pv-FS interneurons by intracellular injections of depolarizing current pulses also triggered Ca2+ elevations and gliotransmitter release from nearby astrocytes which activated NMDAR-mediated slow inward currents in Pv-FS interneurons. Astrocytic glutamate can have on these GABAergic interneurons a dual action that may ultimately: i) oppose seizure generation/spread; ii) favour hyperactivity (by enhancing neuronal synchrony or the depolarizing, excitatory effects of GABA). Clarification of astrocyte-interneuron reciprocal signaling may represent an important step towards a better understanding of the cellular events at the basis of generation, propagation and cessation of focal ictal discharges. References Trevelyan, A. J., Sussillo, D., Watson, B. O. & Yuste, R. Modular propagation of epileptiform activity: evidence for an inhibitory veto in neocortex. J. Neurosci. 26, 12447-12455 (2006). Trevelyan, A. J., Sussillo, D. & Yuste, R. Feedforward inhibition contributes to the control of epileptiform propagation speed. J. Neurosci. 27, 3383-3387 (2007). Cammarota, M., Losi, G., Chiavegato, A., Zonta, M. & Carmignoto, G. Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy. J. Physiol. 591, 807-822 (2013). Keywords: glia, neuronal synchrony, Seizures, inhibition, fast-spiking interneurons Conference: 4th Conference of the Mediterrarnean Neuroscience Society, Istanbul, Turkey, 30 Sep - 3 Oct, 2012. Presentation Type: Symposium Topic: Abstracts Citation: Carmignoto G (2013). Astrocytes and epilepsy. Conference Abstract: 4th Conference of the Mediterrarnean Neuroscience Society. doi: 10.3389/conf.fnhum.2013.210.00013 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2013; Published Online: 11 Apr 2013. * Correspondence: Dr. Giorgio Carmignoto, National Reserch Council (CNR), Institute of Neuroscience and University of Padova, Padova, 35121, Italy, giorgio.carmignoto@bio.unipd.it Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Giorgio Carmignoto Google Giorgio Carmignoto Google Scholar Giorgio Carmignoto PubMed Giorgio Carmignoto Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.