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Slide 25

Block of GABA-A Receptors Results in the Transformation of Spindle Waves into Events that Resemble Absence Seizures.

Spindle waves are normally mediated through the activation of GABA-A receptors on thalamocortical neurons (A). Surprisingly, when these receptors are block with application of bicuculline, the spindle waves are transformed into events that resemble absence seizures (B). During normal spindle waves, the IPSPs are about 100 msec in duration. Block of GABA-A receptors results in the IPSPs being about 300 msec in duration and the oscillation slowing down from 6-10 Hz to about 3 Hz (compare D and E).

Since thalamocortical cells like to burst at 3 Hz, these bursts become very strong. (The intrinsic harmonics of the thalamocortical cells matches that of the thalamocortical-PGN loop.) This results in the generation of a massive synchronized discharge at about 3 Hz. In this manner, normal spindle waves in vitro can be perverted into seizure-like events. These "seizures" are blocked by antagonizing GABA-B receptors, indicating that the slow IPSPs that underlie them are mediated through these receptors.

This result suggests that the GABAergic neurons in the PGN may be discharging very strongly during the generation of the bicuculline-induced paroxysmal activity.