Editors' ChoiceNeuroscience

Seizing the Moment

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Science Translational Medicine  02 Dec 2009:
Vol. 1, Issue 9, pp. 9ec33
DOI: 10.1126/scitranslmed.3000670

Epileptic seizures manifest in various ways and are characterized by the severity and the participating neuronal networks. Petit mal seizures, also known as absence seizures, can sometimes cause an arm to jerk or the eyes to rapidly blink, but they can also have no noticeable symptoms at all except for brief periods of lapses of consciousness. Absence seizures are arise from thalamocortical neuronal networks. Although the differential activation of GABA receptors in the thalamus is known to control the oscillation frequency of thalamocortical networks, the mechanisms underlying the emergence of absence seizures emerge are still unknown. Now, Cope et al. show in a rat polygenic model of general absence epilepsy that aberrant tonic inhibition generated by the GABAA receptor is required for the appearance of absence seizures. The authors found in thalamic slices from diseased rodents that, prior to seizure onset, there is a selective enhancement of GABAA receptor function, a result of inefficient GABA uptake by GABA transporters leading to enhanced tonic current in thalamocortical neurons. In mice lacking GABAA receptors, absence seizures could not be induced with pharmacological agonists, and intrathalamic injection of antisense oligodeoxynucleotides targeting GABAA receptors in rodents significantly reduced the amount of time spent in seizure. Moreover, intrathalamic administration of a GABAA receptor agonist in normal rats initiated absence seizures in rats that do not normally have them, demonstrating that enhanced GABAA receptor function in the thalamus is necessary and sufficient for absence seizures.

D. W. Cope et al., Enhanced tonic GABAA inhibition in typical absence epilepsy. Nat. Med. 22 November 2009 (10.1038/nm.2058) [Abstract]

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