Corticothalamic feedback: a key to explain absence seizures.
In: Computational Neuroscience in Epilepsy, Edited by
Soltesz, I. and Staley, K., Elsevier, Amsterdam, pp. 184-214 (2008).
Over the last years, decisive experimental data have been obtained
concerning the biophysical mechanisms and ion channels properties
important for seizure generation. Computational models have
succeeded in proposing plausible mechanisms to explain the sudden
emergence of hypersynchronized oscillations at ~3 Hz (or 5-10 Hz in
some species), which are associated with "spike-and-wave" complexes
in the electroencephalogram (EEG). The underlying mechanisms of such
seizures involve thalamocortical loops, the particular oscillatory
properties of thalamic neurons, and the particular biophysical
properties of some receptor types (such as the GABAB
receptor). Here, we overview these mechanisms step by step, starting
from the genesis of hypersynchronized oscillations by thalamic
circuits. We next consider how cortical circuits can generate
spike-and-wave EEG patterns. These mechanisms are then merged
together in thalamocortical loops, where we emphasize the central
role played by the "feedback" projections from cortex to thalamus.
If for some reason the corticothalamic feedback becomes too strong,
thalamic circuits can switch to a slower and hypersynchronized
oscillatory mode, which in turn entrains the whole thalamocortical
system into hypersynchronized oscillations with spike-and-wave EEG
patterns. We suggest that the key to explain absence seizures is
this switching mechanism of thalamic circuits, induced by exceedingly
strong corticothalamic feedback. Such a switch was identified in
experiments in vitro, in which oscillatory properties could be
controlled by stimulating corticothalamic fibers. According to this
mechanism, absence seizures result from anomalously high cortical
excitability with a physiologically intact thalamus.
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