期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 9, 页码 3567-3572出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1216958110
关键词
functional connectivity; neuronal networks
资金
- National Institute of Neurological Disorders and Stroke [T32NS045540]
- International Incoming Fellowships Marie Curie Fellowship
- National Institutes of Health [NS35915]
- European Research Council [242852]
- ERA-Net Network of European Funding for Neuroscience Research: EpiNet Grant
- Equipe Fondation pour la Recherche Medicate
- European Research Council (ERC) [242852] Funding Source: European Research Council (ERC)
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 synchronizations are well described at the macroscopic level using electrophysiological 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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