Intracellular correlates of the initiation and propagation of epileptic seizures using a novel chemo-optogenetic model
The goals of this study is to reveal the cellular and synaptic correlates of initiation and spread of epileptic seizures. To these aims, we have developed a new chemo-opto-genetic model for focal epileptic cortical seizures in mice. In this model initial focal seizures are induced chemogenetically by silencing inhibitory cells. Paradoxically, when the same inhibitory cells are optogenetically activated days later, reliable focal initiation of epileptic activity is observed minutes after the termination of light-based activation. Using this model we will test the prevailing hypothesis that initiation and propagation of seizures is caused by increased excitation to inhibition ratio. Moreover we will use this model to reveal the mechanisms by which seizures affect sensory processing and consequently impair perception. Finally, additional genetic methods will be used to identify the underlying mechanisms that promote the propagation of seizures from the site of initiation to distal brain structures. This study will help to understand how seizures initiate and spread to other brain regions and how they affect sensory processing. Such increased understanding may help in designing new therapeutic approaches, aimed to prevent seizure propagation.