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Spatially clustered neuronal assemblies comprise the microstructure of synchrony in chronically epileptic networks

Abstract : Epilepsy is characterized by recurrent synchronizations of neuronal activity, which are both a cardinal clinical symptom and a debilitating phenomenon. Although the temporal dynamics of epileptiform syn-chronizations are well described at the macroscopic level using elec-trophysiological approaches, less is known about how spatially distributed microcircuits contribute to these events. It is important to understand the relationship between micro and macro network activity because the various mechanisms proposed to underlie the generation of such pathological dynamics are united by the assumption that epileptic activity is recurrent and hypersynchronous across multiple scales. However, quantitative analyses of epileptiform spatial dynamics with cellular resolution have been hampered by the difficulty of simultaneously recording from multiple neurons in lesioned, adult brain tissue. We have overcome this experimental limitation and used two-photon calcium imaging in combination with a functional clustering algorithm to uncover the functional network structure of the chronically epileptic dentate gyrus in the mouse pilocarpine model of temporal lobe epilepsy. We show that, under hyperexcitable conditions, slices from the epileptic dentate gyrus display recurrent interictal-like network events with a high diversity in the activity patterns of individual neurons. Analysis reveals that multiple functional clusters of spatially localized neurons comprise epileptic networks, and that network events are composed of the coactivation of variable subsets of these clusters, which show little repetition between events. Thus, these interictal-like recurrent macroscopic events are not necessarily recurrent when viewed at the microcircuit scale and instead display a patterned but variable structure.
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Sarah Feldt Muldoon, Ivan Soltesz, Rosa Cossart. Spatially clustered neuronal assemblies comprise the microstructure of synchrony in chronically epileptic networks. Proceedings of the National Academy of Sciences of the United States of America , National Academy of Sciences, 2013, 110 (9), pp.3567-3572. ⟨10.1073/pnas.1216958110⟩. ⟨hal-01848184⟩



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