AUTHOR=Vannini Eleonora , Restani Laura , Dilillo Marialaura , McDonnell Liam A. , Caleo Matteo , Marra Vincenzo TITLE=Synaptic Vesicles Dynamics in Neocortical Epilepsy JOURNAL=Frontiers in Cellular Neuroscience VOLUME=14 YEAR=2020 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2020.606142 DOI=10.3389/fncel.2020.606142 ISSN=1662-5102 ABSTRACT=

Neuronal hyperexcitability often results from an unbalance between excitatory and inhibitory neurotransmission, but the synaptic alterations leading to enhanced seizure propensity are only partly understood. Taking advantage of a mouse model of neocortical epilepsy, we used a combination of photoconversion and electron microscopy to assess changes in synaptic vesicles pools in vivo. Our analyses reveal that epileptic networks show an early onset lengthening of active zones at inhibitory synapses, together with a delayed spatial reorganization of recycled vesicles at excitatory synapses. Proteomics of synaptic content indicate that specific proteins were increased in epileptic mice. Altogether, our data reveal a complex landscape of nanoscale changes affecting the epileptic synaptic release machinery. In particular, our findings show that an altered positioning of release-competent vesicles represent a novel signature of epileptic networks.