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Proc Natl Acad Sci U S A. 2008 Apr 22;105(16):6179-84. doi: 10.1073/pnas.0801372105. Epub 2008 Mar 28.

Nonrandom connectivity of the epileptic dentate gyrus predicts a major role for neuronal hubs in seizures.

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1
Department of Anatomy and Neurobiology, University of California, 193 Irvine Hall, Irvine, CA 92697, USA. rjmorgan@uci.edu

Abstract

Many complex neuronal circuits have been shown to display nonrandom features in their connectivity. However, the functional impact of nonrandom network topologies in neurological diseases is not well understood. The dentate gyrus is an excellent circuit in which to study such functional implications because proepileptic insults cause its structure to undergo a number of specific changes in both humans and animals, including the formation of previously nonexistent granule cell-to-granule cell recurrent excitatory connections. Here, we use a large-scale, biophysically realistic model of the epileptic rat dentate gyrus to reconnect the aberrant recurrent granule cell network in four biologically plausible ways to determine how nonrandom connectivity promotes hyperexcitability after injury. We find that network activity of the dentate gyrus is quite robust in the face of many major alterations in granule cell-to-granule cell connectivity. However, the incorporation of a small number of highly interconnected granule cell hubs greatly increases network activity, resulting in a hyperexcitable, potentially seizure-prone circuit. Our findings demonstrate the functional relevance of nonrandom microcircuits in epileptic brain networks, and they provide a mechanism that could explain the role of granule cells with hilar basal dendrites in contributing to hyperexcitability in the pathological dentate gyrus.

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PMID:
18375756
PMCID:
PMC2299224
DOI:
10.1073/pnas.0801372105
[Indexed for MEDLINE]
Free PMC Article

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