Rattus norvegicus breed:Wistar Epigenomics. Rattus norvegicus breed:Wistar

Starting from dissociated primary neuronal cells from neonatal rat hippocampus, we demonstrate how a single and transient application of glutamate stimulated neurons to generate spontaneous synchronous spiking activity with further progression into spontaneous seizure-like events after a distinct latency period. Computational analysis and comparison of the observed neuronal activity in vitro with intracranial EEG data recorded from epilepsy patients identified strong similarities, including a related sequence of events with defined onset, progression, and termination. In particular, we show that the temporal development of epileptiform network activity correlated with increased neurite outgrowth and altered branching, increased ratio of glutamatergic over GABAergic synapses, loss of calbindin positive interneurons, as well as genome-wide alterations in DNA methylation. Differentially methylated genes were engaged in various cellular activities related to structure, signaling, and regulation of gene expression.