Characterization of a mice model of human epilepsy with Multi-Electrode Arrays

We applied microelectrode array (MEA) recordings to study the generation and propagation of epileptform activity in various connected regions of cortico-hippocampal slices obtained from SynapsinI/II/III knockout (TKO) mice and the effects of the synaptic vesicle-targeted anti epileptic drug levetiracetam (LEV). Synapsins (SynI, SynII and SynIII) are synaptic vesicle phosphoproteins playing a role in synaptic transmission and plasticity. TKO mice display an epileptic phenotype and mutation of the SYN1 gene is associated with epilepsy in man. We found that both interictal (IIC) and ictal (IC) discharges induced by 4AP were more pronounced and widespread in TKO mice, revealing a state of hyperexcitability of TKO networks. To get insight into the frequencies characterizing the IC seizures, we analyzed the average IC power spectral density (PSD) in the 10-50 Hz range in different cortical regions. TKO slices exhibited an increase of power for frequencies above 20Hz with respect to Wild- Type (TWT). To determine whether the hyperexcitability of TKO slices is also reflected by an increased spread of IC discharges and taking advantage of the spatial resolution of the MEA device, we measured the percentage of electrodes recording IC discharges over the total number of cortical electrodes. The spread of excitation was significantly higher in TKO slices than in TWT ones and treatment with LEV decreased the spread of IC discharges in the entorhinal of TKO slices. In order to better characterize the propagation of the IIC events in the hippocampus, we recently coupled MEA recordings with optical imaging using voltage-sensitive dyes by exploiting the possibility of simultaneous recordings with a high spatial and temporal resolution to reveal more detailed patterns of propagation.