Neurobiology of Epilepsy (Continued)

The cellular events that underlie the ability of NRT neurons to shift between an oscillatory and tonic firing mode are the low-threshold (T) Ca²⁺ spikes that are present in thalamocortical and NRT neurons. These T-type Ca²⁺ channels are a key membrane property involved in burst-firing excitation and are associated with the change from oscillatory to burst-firing in thalamocortical cells. Mild depolarization of these neurons is sufficient to activate these channels and to allow the influx of extracellular Ca²⁺. Further depolarization produced by Ca²⁺ inflow will exceed the threshold for firing a burst of action potentials. After T-channels are activated, they become inactivated rather quickly, hence the name transient. Deinactivation of T-channels requires a relatively lengthy hyperpolarization. GABA_B receptor–mediated hyperpolarization is a primary factor in the deinactivation of T-channels.

Recurrent collateral GABAergic fibers from the NRT neurons activate GABA_A receptors on adjacent NRT neurons. Activating GABA_A receptors in the NRT therefore results in an inhibition of inhibitory output to the thalamic relay neurons. Because of the decreased GABA_B activation, there would be a reduced likelihood that Ca²⁺ deinactivation would occur. This would result in decreased oscillatory firing. However, direct GABA_A and GABA_B activation of thalamic relay neurons would be expected to have detrimental effects, increasing hyperpolarization and therefore increasing the likelihood of deinactivation of the T-channels. The abnormal oscillatory rhythms in absence seizures can be caused by abnormalities of the T-type Ca²⁺ channels or enhanced GABA_B function.