Abstracts

Memory disturbances are often observed in patients with epilepsy. With the kindling of seizures, a model of temporal lobe epilepsy, memory impairments occur that are specific to the site stimulated and persist in the interictal period. Kindling-induced alterations of behavior associated with various structures are consistent with the effects of lesions and activation of the same structures. In light of recent research indicating that the entorhinal cortex plays a critical role in spatial memory, we examined the effects of entorhinal kindling on spatial learning and memory. Bipolar electrodes were surgically implanted into either the lateral or medial entorhinal cortex (LEC or MEC) of adult male Long-Evans rats. After a recovery period, the afterdischarge threshold was determined; subsequently rats received kindling stimulation once daily until 5 generalized seizures developed. Stimulation was then suspended, and two days later water maze testing commenced consisting of: Day 2, 6 visible platform trials; Day 3, 18 acquisition trails and 1 probe trial; and Days 10 and 31, 3 retention trials and 1 probe trial. Nonkindled yoked control rats were also tested. On visible platform trials, all groups required similar distances and latencies to mount the visible platform, indicating that entorhinal kindling did not produced motivational or sensorimotor deficits. On submerged platform trials, the acquisition performance of the LEC kindled group was comparable to controls. However, 30 percent of the MEC kindled group failed to acquire the platform[apos]s location throughout the 18 acquisition trails, whereas the remainder of the MEC kindled group performed similarly to the control group. In retention testing, both the LEC and the MEC kindled groups displayed increased latency and distance as compared to controls during retention trials on day 28, but not day10. Although LEC kindling failed to affect spatial learning, 30 percent of the MEC kindled group failed to learn the position of the platform. In addition, both LEC and MEC kindling disrupted spatial memory measured 1 month after acquisition, suggesting that the persistence of memory was more fragile after entorhinal kindling. Recent evidence suggests that the firing patterns of neurons in caudal MEC change depending on the rat[apos]s spatial location. Furthermore, the MEC is monosynaptically connected with the septal dentate gyrus, which is important in spatial cognition. Thus it is not surprising that MEC kindling in particular affects spatial cognition. The kindling-induced learning and memory deficits we observed support the hypothesis that kindling produces site specific alterations in neuronal function. (Supported by a Discovery Grant from NSERC awarded to MEC.)