Slide 28

The normal generation of spindle waves involves a cyclical interaction between thalamocortical relay cells and the GABAergic neurons of the perigeniculate nucleus. PGN neurons burst and inhibit thalamocortical cells. Some of these rebound burst and re-excite the PGN cells. The generalization of this activity throughout the network results in propagation of the oscillation and the "waxing" of the spindle wave in the EEG. Normally, PGN cells inhibit one and another and therefore regulate the amplitude of each burst of action potentials during spindle wave generation.

The block of GABA-A receptors with bicuculline results in removal of the PGN to PGN cell inhibition. This results in a greatly enhanced duration and amplitude of action potential bursts in PGN cells. The enhanced release of GABA is proposed to result in strong activation of GABA-B receptors on thalamocortical neurons. This results in a slow, long duration IPSP in thalamocortical cells that is particularly effective in activating large rebound low threshold Ca2+ spikes. The subsequent strong bursts of action potentials in thalamocortical cells excites PGN neurons even more, resulting in a positive feedback loop and the generation of seizures.

Finally, we get to the last question of this talk:

How is it that the synchronized oscillations of sleep disappear in the transition to the waking state and what neurotransmitters mediate this?