Aim: 

Epilepsy has a strong genetic component. Mutant mice lacking synapsins (Syn), a family of synaptic vesicles (SV) proteins principally implicated in the regulation of neurotransmitter release, are epileptic. The attacks appear after the third month of age and their severity increases with age. Recently mutations of Syn genes have been found in patients with epilepsy.

Methods: 

We used Micro-Electrode Arrays to study spontaneous and chemically evoked epileptiform activities in horizontal brain slices, obtained from wild-type (WT) and SynKO mice.

Results: 

6-months old SynKO mice show spontaneous sporadic ictal (IC) events in the entorhinal cortex. The application of convulsant agent 4-aminopyridine (4AP), elicits IC and I-IC events in both WT and SynKO slices. In the hippocampus of young SynKO mice, 4AP induces I-IC events with a higher frequency than in WT mice. Also the frequency of IC events, mainly observed in the cortex, is higher in SynKO animals. The analysis of adult mice revealed a clear age-related aggravation, which paralleled the increase in the severity of the epileptic phenotype observed in vivo. More than 60% of slices from adult SynKO mice showed an IC event, while WT slices were refractory at this age to experience IC activity.

Conclusion: 

Our data show that acute brain slices obtained from SynKO mice represent a reliable in vitro model of human epilepsy, useful to study how neuronal network hyperexcitabilty due to mutations in SV proteins leads to the development of epileptiform activity.