Abstracts

Low frequency stimulation (LFS) applied to the amygdala or hippocampus has the ability to change the threshold for triggering focal seizure activity and/or alter kindling epileptogenesis. Here, we questioned whether the suppressive effect of LFS was only associated with the kindling electrode itself, or was evident when applied to the general area in which the kindling electrode resided. Genetically seizure-prone Fast kindling rats were implanted in one amygdala area with two electrodes. One electrode, consisting of typical bipolar construction, involved two twisted wires whose tips were separated by the thickness of the insulation (called the [apos]tight[apos] electrode). It was positioned in the basolateral amygdala. The second or [apos]spanning[apos] electrode was similar in construction, however, one of its poles was positioned 2mm anterior and the other 2 mm posterior to the tight electrode. The spanning electrode also had 2 mm of insulation removed from its tips to increase its area of activation. After first kindling the tight electrode and determining stability of its afterdischarge threshold (ADT), a single session of 1 Hz stimulation at 100 [mu]A was applied to that electrode for 90 sec, and its ADT redetermined one min later. Without reapplication of the LFS, the ADT at the tight electrode was redetermined each day for the next 5 days. In the second experiment, a new stable ADT was determined at the tight electrode. This was followed the next day by LFS to the spanning electrode and then measuring its impact on the ADTs of the tight electrode in the same temporal sequence as above. In the concluding experiment, increases in the intensity and/or duration of LFS to the spanning electrode occurred before various ADT tests at the tight electrode. LFS applied to the kindled tight electrode produced a 200-500% increase in the ADT at that site, which declined slowly over days. A much smaller and shorter increase in the ADTs at the tight electrode was evident after moderate LFS was applied to the spanning electrode. In contrast, high intensity (600 [mu]A) LFS applied to the spanning electrode produced a 500% increase in the tight electrode ADTs for a few days, which dissipated. Lastly, and unexpectedly, longer duration (5 min) LFS at the spanning electrode created a neurological environment where reaching the ADT at the tight electrode provoked status epilepticus or continuous electrographic seizures with occasional convulsive seizures for hours. Not surprisingly, this activity was followed by a significant and unrelenting elevation of the tight electrode ADTs, yet little histological damage was evident. Sufficient intensity of LFS can induce substantial elevation in the threshold for triggering an afterdischarge in a kindled amygdala. However, with longer durations of LFS, conditions conducive for status epilpticus can be engaged, suggesting empirically-derived care should be realized in the application of such treatment. (Supported by CIHR and NSERC to DCM.)