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Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits

Nature Medicine volume 5, pages 888–894 (1999)Cite this article

Abstract

Febrile (fever-induced) seizures affect 3–5% of infants and young children. Despite the high incidence of febrile seizures, their contribution to the development of epilepsy later in life has remained controversial. Combining a new rat model of complex febrile seizures and patch clamp techniques, we determined that hyperthermia-induced seizures in the immature rat cause a selective presynaptic increase in inhibitory synaptic transmission in the hippocampus that lasts into adulthood. The long-lasting nature of these potent alterations in synaptic communication after febrile seizures does not support the prevalent view of the 'benign' nature of early-life febrile convulsions.

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Figure 1: Hyperthermia-induced seizures result in a GABAA receptor-dependent, long-term depression of the discharges of CA1 pyramidal cells.
Figure 2: The GABAA receptor-mediated inhibitory postsynaptic currents in CA1 pyramidal cells is enhanced in rats that experienced seizures.
Figure 3: The frequency, but not the amplitude, of the miniature IPSCs (mIPSCs) is increased in rats that experienced seizures.
Figure 4: The effects of protein kinase blockers on the enhanced amplitude of the evoked IPSCs in CA1 pyramidal cells after hyperthermia-induced seizures.

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Acknowledgements

We thank M. Ahmadi and R. Zhu for technical assistance. This work was financially supported by NIH (NS35439 to T.Z.B. and NS38580 to I.S.), by UC Systemwide Biotechnology Research and Education Program (BREP-98-02 to T.Z.B. & I.S.) and by the Epilepsy Foundation of America (EFA-24106 to I.S).

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, University of California, Irvine, 92697-1280, California

    Kang Chen, Tallie Z. Baram & Ivan Soltesz

  2. Department of Pediatrics, University of California, Irvine, 92697-1280, California

    Kang Chen & Tallie Z. Baram

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Correspondence to Ivan Soltesz.

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Chen, K., Baram, T. & Soltesz, I. Febrile seizures in the developing brain result in persistent modification of neuronal excitability in limbic circuits. Nat Med 5, 888–894 (1999). https://doi.org/10.1038/11330

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