Intermediate Stage of Epileptogenesis Is Not Affected by Disrupting Memory Consolidation Processes.

Abstract

Epilepsy affects 50 to 70 million people worldwide and is characterized by recurring seizures that accelerate neurodegeneration; however, its mechanisms are still not well understood. It was proposed that epileptogenesis may be "hijacking" the mechanisms underlying normal memory formation, where synapses involved in seizure activity are strengthened after each seizure, similarly to the strengthening of memories during the consolidation processes. To investigate this link, we used a kindling model of temporal lobe epilepsy in mice and tested whether disrupting memory consolidation could alter epileptogenesis. Animals were kindled until stage 3 behavioral seizures on the Racine scale were reached. In subsequent sessions, rapamycin was administered within 10 min following kindling to inhibit protein synthesis essential for memory consolidation in the neurons involved in a seizure. Rapamycin reduced the freezing response to sensory stimuli preceding a seizure, suggesting that memory consolidation was disrupted; however, epileptogenesis was not affected. Additionally, we tested whether administering isoflurane, which reduces neuronal activity, could weaken seizure-associated patterns by interfering with memory reconsolidation processes. This intervention also did not reduce the intensity of seizures. Altogether, these preliminary results appear to be inconsistent with the hypothesis that epileptogenesis involves the same mechanisms as memory formation processes.