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The activity within the CA3 excitatory network during Theiler's virus encephalitis is distinct from that observed during chronic epilepsy

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Abstract

Viral infections of the central nervous system (CNS) are associated with an increased risk for seizures during the acute infection period and the subsequent development of chronic epilepsy that is often difficult to treat. In previous work, we have shown that mice of the C57BL/6 strain infected with Theiler's murine encephalomyelitis virus (TMEV) exhibit a similar sequence, thereby providing a potential useful model of virus-induced epilepsy. The present study examines spontaneous and miniature excitatory postsynaptic currents in CA3 pyramidal cells recorded from brain slices prepared during both the acute phase during encephalitis and 2 months following TMEV infection. Animals that develop chronic epilepsy following TMEV infection exhibit considerable hippocampal sclerosis, directly implicating this brain region in the process of epileptogenesis. There are significant increases in amplitude and frequency of spontaneous and miniature excitatory currents in CA3 cells recorded in brain slices prepared during the acute infection period and 2 months after infection. However, the patterns of changes observed are markedly different during these two periods, suggesting that there are underlying changes in the network over time. These differences have implications for the treatment used during the acute infection and after chronic seizures develop.

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Acknowledgments

The authors would like to acknowledge the financial support of Robert and Joyce Rice (Salt Lake City, UT), the Margolis Foundation (Salt Lake City, UT), Citizens United for Research in Epilepsy (HSW and RSF), National Institutes of Health 1R01NS065714 (RSF), the Epilepsy Foundation (KAS), and the American Epilepsy Society (KAS), the Dumke Foundation (KSW) and National Institutes of Health R21 NS41673 (KSW). We would also like to thank Dr. Alla Borisyuk for advice about data analysis.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, University of Utah, 417 Wakara Way, Suite 3211, Salt Lake City, UT, 84108, USA

    Roy M. Smeal, H. Steve White & Karen S. Wilcox

  2. Interdepartmental Program in Neuroscience, University of Utah, 401 MREB, 20N 1900 E, Salt Lake City, UT, 84132, USA

    Kerry-Ann Stewart, Eli Iacob, H. Steve White & Karen S. Wilcox

  3. Department of Pathology, University of Utah, 15 N Medical Drive East, Salt Lake City, UT, 84112, USA

    Robert S. Fujinami

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  1. Roy M. Smeal
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Correspondence to Roy M. Smeal.

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Smeal, R.M., Stewart, KA., Iacob, E. et al. The activity within the CA3 excitatory network during Theiler's virus encephalitis is distinct from that observed during chronic epilepsy. J. Neurovirol. 18, 30–44 (2012). https://doi.org/10.1007/s13365-012-0082-5

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