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Recurrent neonatal seizures result in long-term increases in neuronal network excitability in the rat neocortex. Eur J Neurosci 2010 Apr;31(8):1446-55



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Scopus ID

2-s2.0-77951155970   42 Citations


Neonatal seizures are associated with a high likelihood of adverse neurological outcomes, including mental retardation, behavioral disorders, and epilepsy. Early seizures typically involve the neocortex, and post-neonatal epilepsy is often of neocortical origin. However, our understanding of the consequences of neonatal seizures for neocortical function is limited. In the present study, we show that neonatal seizures induced by flurothyl result in markedly enhanced susceptibility of the neocortex to seizure-like activity. This change occurs in young rats studied weeks after the last induced seizure and in adult rats studied months after the initial seizures. Neonatal seizures resulted in reductions in the amplitude of spontaneous inhibitory postsynaptic currents and the frequency of miniature inhibitory postsynaptic currents, and significant increases in the amplitude and frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and in the frequency of miniature excitatory postsynaptic currents (mEPSCs) in pyramidal cells of layer 2/3 of the somatosensory cortex. The selective N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonovalerate eliminated the differences in amplitude and frequency of sEPSCs and mEPSCs in the control and flurothyl groups, suggesting that NMDA receptors contribute significantly to the enhanced excitability seen in slices from rats that experienced recurrent neonatal seizures. Taken together, our results suggest that recurrent seizures in infancy result in a persistent enhancement of neocortical excitability.

Author List

Isaeva E, Isaev D, Savrasova A, Khazipov R, Holmes GL


Olena Isaeva PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals, Newborn
Excitatory Amino Acid Antagonists
Excitatory Postsynaptic Potentials
In Vitro Techniques
Inhibitory Postsynaptic Potentials
Neural Pathways
Pyramidal Cells
Rats, Sprague-Dawley
Receptors, N-Methyl-D-Aspartate
Somatosensory Cortex
Time Factors