Project Title:

Astrocytic plasticity and dysfunctions in the cortical “initiation site” of absence seizures

Francis Delicata

Objectives:

The cellular, molecular and synaptic abnormalities of the putative “cortical initiation site” of absence seizures are largely unknown, and limited available work has only focused on neuronal deficits. Here, we will test the hypothesis that the underlying dysfunction at the “cortical initiation site” is astrocytic.

Methodology:

The project will start by investigating the relative hyperexcitability of astrocytes compared to neurons, using patch-clamp recordings, alone or combined with Ca2+ imaging, thereby providing a systematic characterization of astrocytic and neuronal dysfunctions in this cortical area. Using selective optogenetic stimulation (light activation of the opto-alpha1 adrenergic receptor and ChR2 targeted cell type-selectively to astrocytes and neurons), the mechanisms of intercellular communication will be investigated in non-epileptic animals and in genetic models of AE.

Rheinallt Parri