Abstracts

Rationale: Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are paradoxically resistant to the progression of amygdaloid kindling. Rhythmic reciprocal oscillatory firing between the cortex and the thalamus plays a critical role in absence seizures. We hypothesized that, the progression to the later (convulsive) stages of amygdala involves acquired alterations to firing properties in the thalamic reticular nucleus (TRN) that predisposes to rhythmic synchronized epileptiform thalamo-cortical (TC) firing, and that baseline perturbations in TRN neurons in GAERS renders them resistant to this change. Methods: Extracellular single neuron recordings were performed in-vivo under neurolept anesthesia in GAERS and non-epileptic control (NEC) rats chronically implanted with a stimulating bipolar electrode in the left amygdala along with the cortical EEG. The recordings were performed in region of the thalamus, critical to the oscillatory TC rhythms that underlie absence seizures, the inhibitory TRN and ventrobasal thalamus (VB). The location of the recorded cells was confirmed histologically at the end of each experiment. Kindling stimulations were delivered at afterdischarge thresholds to reach Class 5 seizure (maximum stimulations=30). Results: The interictal firing patterns recorded in TRN were similar between non-kindled GAERS (n=10 cells, 5 rats) and NEC rats (n=6 cells, 3 rats) in all parameters examined (mean firing frequency, % burst firing, mean number of action potentials (APs) per burst, maximum number of AP/burst and intraburst firing frequency). In kindled NEC rats (n=10 cells, 6 rats) the TRN firing had evolved to a bursting (epileptiform), low frequency pattern, but this was not seen in GAERS (n=18 cells, 5 rats) subjected to the same number of stimulations as kindled NEC rats (Table 1). The thalamocortical cells in the VB thalamus in kindled NECs (n=19 cells, 8 rats) interictally had a lower firing frequency and more burst firing compared to GAERS (n=8 cells, 5 rats) subjected to the same number of stimulations. During a kindling seizure in control rats the firing pattern in TRN neurons was affected early in the seizure, with rhythmic synchronized burst firing (sometimes precede by a brief suppression) (n=18 cells, 5 rats). However, in GAERS the TRN firing engaged only late in the seizure or not at all (n=10 cells, 6 rats). Conclusions: This is the first in-vivo study of the effect of amygdala kindling on single neuron firing patterns in TC circuits. Kindling induces the thalamus (TRN and VB) to fire in a lower frequency bursting (epileptiform) pattern, which may play a mechanistic role in the synchronized TC firing underlying the secondary generalization of the limbic seizures. GAERS do not show this alteration in thalamic neuronal firing pattern, consistent with their resistance to developing secondary convulsive seizures. These findings provide new insights into the nature of the involvement of the thalamus during secondary generalization of limbic seizures.