The Journal of Neuroscience, February 15, 2001, 21(4):1378-1384
Contribution of GABAA and GABAB Receptors
to Thalamic Neuronal Activity during Spontaneous Absence Seizures in
Rats
Rainer
Staak and
Hans-Christian
Pape
Institute of Physiology, Medical School, Otto-von-Guericke
University, 39120 Magdeburg, Germany
The contribution of GABAergic mechanisms in thalamic relay nuclei
to spike and wave discharges (SWDs) during spontaneous seizures was
assessed using the WAG/Rij strain of rats, an established genetic model of absence epilepsy, in combination with single-unit recordings and microiontophoretic techniques in the ventrobasal thalamic complex in vivo. Spontaneous SWDs
occurring on the electroencephalogram at 5-9 Hz were associated with
burst firing in thalamocortical neurons, which was phase-locked with
the spike component. Microiontophoretic application of the
GABAA receptor antagonist bicuculline significantly increased the magnitude of SWD-related firing in all tested cells. Application of the GABAB receptor antagonist CGP 55845A
exerted a statistically insignificant modulatory effect on neuronal
activity during spontaneous SWDs but significantly attenuated the
bicuculline-evoked aggravation of SWD-related firing. The data indicate
that, in thalamocortical neurons, (1) GABAA
receptor-mediated events are recruited with each SWD, (2) SWD-related
activity can be evoked with no significant contribution of
GABAB receptors, and (3) blockade of GABAA
receptors potentiates SWD-related activity, presumably through an
indirect effect mediated through GABAB receptors. These results vote against a predominant or even exclusive contribution of
GABAB receptors to spontaneous SWDs in thalamic relay
nuclei in the WAG/Rij strain, but rather point to a critical role of GABAA receptor activation. This conclusion is in support of
the view that the two subtypes of GABA receptors play a differential role in fast (5-10 Hz) and slow (3 Hz) spike-wave paroxysms observed during absence seizures.
Key words:
absence epilepsy; spike and wave discharges; thalamus; GABAA; GABAB; microiontophoresis; GAERS; WAG/Rij
Copyright © 2001 Society for Neuroscience 0270-6474/01/2141378-07$05.00/0
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