Abstracts

Rationale: Basal ganglia dysfunctions are increasingly described not only for experimental but also for clinical epilepsy. Several imaging studies revealed changes in the striatum of epileptic patients. A more detailed analysis of striatal dysfunctions on the cellular level is possible with animal models of epilepsy. A recent in-situ hybridization study of the striatum in amygdala-kindled rats, a model of temporal lobe epilepsy, revealed a long-lasting increased staining of GABAergic interneurons in the left anterior striatum. This was hypothesized to decrease inhibitory striatal output. The substantia nigra pars reticulata (SNr), which receives direct and indirect input from the striatum, consequently showed disinhibited spontaneous activity as revealed previously by in-vivo single-unit recordings in amygdala-kindled rats. These results prompted us to investigate the electrophysiological properties of striatal neurons in this rat kindling model of temporal lobe epilepsy. Methods: Adult female Wistar rats were implanted with a bipolar stainless steel kindling electrode into the right basolateral amygdala. After a recovery period of two weeks, the animals were stimulated until 10 secondarily generalized seizures were evoked. Extracellular in-vivo single-unit recordings were performed bilaterally in the anterior striatum 24 hrs after a generalized kindled seizure. Non-stimulated rats with kindling electrode (sham-kindled) and naive rats served as controls. Results: Analysis of firing rates revealed a significantly increased activity of GABAergic neurons in the left anterior striatum in amygdala-kindled rats compared to sham-kindled and naive controls. This alteration was restricted to the dorsolateral subregion of the left striatum (p<0.05, Kruskal-Wallis-ANOVA followed by Mann-Whitney U-test). Evaluation of recordings revealed a burst-like behavior of striatal neurons in amygdala-kindled rats as well as in sham-kindled and naive rats, indicating that the recorded neurons resemble striatal output neurons. However, the used method did not allow us to reliably assign these findings to a specific neuronal population of the striatum. Conclusions: The present data support the assumption of an abnormal basal ganglia circuit in amygdala-kindled rats. In line with the previous in-situ hybridization study mentioned above we now showed functional alterations in the anterior left striatum of kindled rats. Assuming the recorded neurons resemble striatal output neurons, the observed hyperactivity is possibly generated from compensatory mechanisms in this brain region. The detected restriction of hyperactive striatal neurons to the dorsolateral subregion is consistent with literature data which showed a somatotopic organization of the striatum. The dorsolateral part of the rat striatum is thought to be involved in forelimb movement and postural control. The findings add to a better understanding of the pathophysiology of the basal ganglia circuit. It may help to select appropriate targets for therapeutic interventions such as deep brain stimulation in pharmacoresistant epilepsy. Supported by the DFG (Ge1103/6)