Enhanced sequential reaction time task performance in a rat model of mesial temporal lobe epilepsy with classic hippocampal sclerosis

Abstract

The human serial reaction time task (SRTT) has widely been used to study the neural basis of implicit learning. It is well documented, in both human and animal studies, that striatal dopaminergic processes play a major role in this task. However, findings on the role of the hippocampus - which is mainly associated with declarative memory - in implicit learning and performance are less univocal. We used a SRTT to evaluate implicit learning and performance in rats with perforant pathway stimulation-induced hippocampal neuron loss; a clinically-relevant animal model of mesial temporal lobe epilepsy (MTLS-HS). As has been previously reported for the Sprague-Dawley strain, 8h of continuous stimulation in male Wistar rats reliably induced widespread neuron loss in areas CA3 and CA1 with a characteristic sparing of CA2 and the granule cells. Histological analysis revealed that hippocampal volume was reduced by an average of 44%. Despite this severe hippocampal injury, rats showed superior performance in our instrumental SRTT, namely shorter reaction times, and without a loss in accuracy, especially during the second half of our 16-days testing period. These results demonstrate that a hippocampal lesion can improve performance in a rat SRTT, which is probably due to enhanced instrumental performance. In line with our previous findings based on ibotenic-acid induced hippocampal lesion, these data support the hypothesis that loss or impairment of hippocampal function can enhance specific task performance, especially when it is dependent on procedural (striatum-dependent) mechanisms with minimal spatial requirements. As the animal model used here exhibits the defining characteristics of MTLE-HS, these findings may have implications for the study and management of patients with MTLE.