The Role Of High Frequency Oscillations And Interictal Spiking In Hippocampal Epileptogenesis Assessed By In Vivo Electrophysiology, Molecular Cell Biology And Computer Modelling
Epileptic syndromes are one of the most frequent neurological diseases affecting 0.5-3% of the globe's population. This disease causes both suffering and stigmatization of patients and represents an important socio-economic burden for the society.
A better understanding of the fundamental processes that lie at the basis of epileptogenesis is essential for the improvement of the treatment of these patients which in term leads to the amelioration of the quality of life. This research application studies the hyperexcitability of neuronal populations during the development of epilepsy. The results of the study should lead to changes in the therapeutic strategies for epileptic patients.
There are several electrical phenomena associated with epilepsy among which high frequency oscillations (HFO) and interictal spikes (ISp). HFO can be reproduced in a large number of experimental and/or clinical paradigms and it seems to be related to normal and pathological synchronization of the central nervous system. ISp are morphologically defined, episodic, transient discharges of a neuronal population. The relationship of HFO, ISp and epileptic seizures has not been elucidated completely yet, although ISp are present at the vast majority of epileptic patients.
Our hypothesis is that high frequency oscillations produced by a small volume of nervous tissue with morphological/molecular modifications and pathologically synchronized activity can induce isp resulting later in the consolidation and expansion of pathologic activity and the initiation of epileptic seizures.
To study this hypothesis we will implement a relatively new in vivo experimental model of epilepsy which involves mild kindling. We will implant stimulation and recording electrodes to Wistar rats and later record simultaneously and repeatedly the electrocorticogramm and hippocampal field potential. We will study the occurrence, temporal evolution and implication in epileptogenesis of HFO and ISp. Using immunohistochemistry and RT-QPCR the cellular/molecular basis of these electrophysiological modifications will be assessed. Finally we will construct computational models of neural networks capable of reproducing the in vivo observed hfo and we will study the factors contributing to the generation and modulation of these oscillations. The results of this study may open the way for developing truly antiepileptic drugs instead of anticonvulsive ones.