Effects of brain-derived neurotrophic factor and noise on transitions in temporal lobe epilepsy in a hippocampal network

Brain-derived neurotrophic factor (BDNF) has recently been implicated in the modulation of receptor activation leading to dynamic state transitions in temporal lobe epilepsy (TLE). In addition, the crucial role of neuronal noise in these transitions has been studied in electrophysiological experiments. However, the precise role of these factors during seizure generation in TLE is not known. Building on a previously proposed model of an epileptogenic hippocampal network, we included the actions of BDNF-regulated receptors and intrinsic noise. We found that the effects of both BDNF and noise can increase the activation of N-methyl-D-aspartate receptors leading to excessive C a 2 + flux, which induces abnormal fast spiking and bursting. Our results indicate that the combined effects have a strong influence on the seizure-generating network, resulting in higher firing frequency and amplitude. As correlations between firing increase, the synchronization of the entire network increases, a marker of the ictogenic transitions from normal to seizures-like dynamics. Our work on the effects of BDNF dynamics in a noisy environment might lead to an improved model-based understanding of the pathological mechanisms in TLE.