Reports indicate that the amygdala, a limbic structure, is intimately involved in cases of intractable temporal lobe epilepsy. In this proposal, a model of human temporal lobe epilepsy will be used, namely, kindling using the amygdala as the focus. The amygdala focus resembles human temporal lobe epilepsy in resistance to antiepileptic drugs and in the behavioral characteristics of the kindled seizure. To promote an appropriate therapy it is essential to understand the etiology of temporal lobe epilepsy. The long term goals of this research are to elucidate the membrane or cellular mechanisms which underlie the kindling phenomenon in the amygdala and ultimately, through physiological and pharmacological analyses of these mechanisms, to suggest a rational basis for the pharmacological treatment of intractable temporal lobe epilepsy. Intracellular recordings from an in vitro rat brain slice preparation of the amygdaloid complex will be used to address three specific aims: I. to analyze and characterize in vitro the intrinsic electrophysiological properties of individual neurons in the basolateral nuclei at the focus (implanted side) of the amygdaloid complex as a result of kindling in vivo in the basolateral nucleus of the rat. The animals will be tested 28 days after reaching stage 5 of kindling. Changes in the membrane properties would refect alterations in ionic currents and channels underlying those parameters. The contralateral amygdala will also be analyzed. II. To compare the synaptic responses of basolateral cells on the contralateral side to stimulation of afferent input from the stria terminalis and the amygdalofugal pathway (in the area of the median forebrain bundle) in control and kindled animals and to assess the neurotransmitter systems which may be altered as a result of kindling. III. Because recent data suggest kindling may affect individual brain nuclei in different ways, the electrophysiological changes that occur in the ipsilateral central nucleus will be compared with those that occur in the basolateral nuclei. Results obtained from these experiments will provide essential information about the kindling phenomenon. This information will be directly applicable to our understanding of epileptogenesis involving the amygdala in human complex partial seizures.
Showing the most recent 10 out of 23 publications
