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The Journal of Neuroscience, March 18, 2009, 29(11):3660-3671; doi:10.1523/JNEUROSCI.5309-08.2009

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Neurobiology of Disease
The Cause of the Imbalance in the Neuronal Network Leading to Seizure Activity Can Be Predicted by the Electrographic Pattern of the Seizure Onset

Anatol Bragin,^1,3 Avetis Azizyan,¹ Joyel Almajano,¹ and Jerome Engel Jr^1,2,3

Departments of ¹Neurology and ²Neurobiology, and ³The Brain Research Institute, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, California 90095

Correspondence should be addressed to either Anatol Bragin or Jerome Engel Jr at the above address, Email: abragin{at}ucla.edu or Email: engel{at}ucla.edu

This study investigates the temporal dynamics of ictal electrical activity induced by injection of the GABA_A receptor antagonist bicuculline, and the glutamate agonist kainic acid, into the CA3 area of hippocampus. Experiments were conducted in freely moving adult Wistar rats implanted with microelectrodes in multiple brain areas. Wide-band electrical activity (0.1–3000 Hz) was recorded, and the latency of seizure onset as well as the pattern of electrical activity were investigated for each drug. The latencies between injection and the occurrence of first epileptiform events were 3.93 ± 2.76 (±STD) min for bicuculline and 6.37 ± 7.66 min for kainic acid, suggesting the existence of powerful seizure-suppressive mechanisms in the brain. Bicuculline evoked high-amplitude rhythmic epileptiform events at the site of injection which resembled interictal EEG spikes and rapidly propagated to adjacent and remote brain areas. Kainic acid evoked a completely different pattern with a gradual increase in the amplitude of 30–80 Hz activity. Whereas there was strong temporal correlation between EEG events at the site of bicuculline injection and discharges in distant areas, much less correlation was seen with kainic acid injection. Both patterns were followed by generalized ictal EEG discharges and behavioral seizures. Our results illustrate that the same area of the brain can trigger seizures with different electrographic patterns. The knowledge of the network mechanisms underlying these two distinct electrographic patterns might be helpful in designing differential strategies for preventing seizure occurrence.

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Received Nov. 4, 2008; revised Feb. 10, 2009; accepted Feb. 15, 2009.

Correspondence should be addressed to either Anatol Bragin or Jerome Engel Jr at the above address, Email: abragin{at}ucla.edu or Email: engel{at}ucla.edu

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