The effect of amygdala kindling on neuronal firing patterns in the lateral thalamus in the GAERS model of absence epilepsy

Abstract

SUMMARYObjective: The co-occurrence of absence and mesial temporal lobe epilepsy is rare in both humans and animal models. Consistent with this, rat models of absence epilepsy, including genetic absence epilepsy rats from Strasbourg (GAERS), are resistant to experimental temporal lobe epileptogenesis, in particular by amygdala kindling. Structures within the cortical-thalamocortical system are critically involved in the generation and maintenance of the electrographic spike-and-wave discharges (SWDs) that characterize absence seizures. Using in vivo electrophysiologic recordings, this study investigated the role of thalamocortical circuitry in the generalization of amygdalakindling induced seizures in the GAERS and the nonepileptic control (NEC) strain of Wistar rats. Methods: GAERS and NEC rats were implanted with a stimulating electrode in amygdala and stimulated at afterdischarge threshold twice daily to a maximum number of 30 stimulations. Thereafter extracellular single neuron recordings were performed in vivo under neuroleptanesthesia in the thalamocortical network. Results: In NEC rats, amygdala kindling induced convulsive class V seizures and altered characteristics of neuronal activity in the thalamic reticular nucleus (TRN), in particular decreased firing rates and increased burst firing patterns. Less marked changes were seen in other regions examined: the ventroposteromedial nucleus of thalamus (VPM), the CA3 region of the hippocampus, and the deep layers (V/VI) of the cortex. GAERS did not progress beyond class II seizures, with a matched number of kindling stimulations, and the thalamic neuronal firing alterations observed in NEC rats were not seen. Significance: These data suggest that the TRN plays an important role in kindling resistance in GAERS and is central to the control of secondary generalization of limbic seizures.

Mapping Epileptic Activity: Sources or Networks for the Clinicians?

“…Spontaneous epileptic disease occurs in animals, as in the case of the genetic absence epileptic rats of Strasbourg (GAERS) or in the WAG/Rij rats (225–227); other models studied are epileptic conditions induced by – mainly – chemical or electrical interventions (220). A major animal model of TLE is the kainate, or pilocarpine, model of hippocampal sclerosis (HS) (228–232).…”

“…Different animal models of focal epilepsy exist (220), such as the kainate- or pilocarpine-models of MTLE (228, 229, 260), posttraumatic epilepsy (261, 262), or electrical kindling (227, 263). Despite an initially focal insult, recent evidence (e.g., 242) shows that remote brain areas become affected by the pathological activity of the epileptic focus.…”

“…Carcak et al (227) took advantage of the fact that absence epilepsy may increase the resistance to limbic seizures. They investigated the role of the cortico-thalamo-cortical circuitry, involved in SWDs, in the development of limbic seizures induced by unilateral electrical stimulation of the rat amygdala.…”

“…They investigated the role of the cortico-thalamo-cortical circuitry, involved in SWDs, in the development of limbic seizures induced by unilateral electrical stimulation of the rat amygdala. Whereas control rats, i.e., those without absence epilepsy, presented all convulsive epileptic seizures following amygdala electrical stimulation, rats suffering from absence epilepsy did not (227). In order to understand how the circuit involved in absence epilepsy could affect the one of TLE, the authors investigated the spontaneous activity in the reticular thalamic nucleus (RTN), known to be involved in the slow-waves discharges that characterize absence epilepsy (227).…”

“…Whereas control rats, i.e., those without absence epilepsy, presented all convulsive epileptic seizures following amygdala electrical stimulation, rats suffering from absence epilepsy did not (227). In order to understand how the circuit involved in absence epilepsy could affect the one of TLE, the authors investigated the spontaneous activity in the reticular thalamic nucleus (RTN), known to be involved in the slow-waves discharges that characterize absence epilepsy (227). Remarkably, the electrical stimulation of the amygdala had a different effect on the mean firing frequency of neurons of the RTN: in not-stimulated animals, there was no significant difference between epileptic and non-epileptic rats, whereas the increase after stimulation was higher in epileptic rats when compared to non-epileptic rats (227).…”