RT Journal Article SR Electronic T1 Focal epilepsy modulates vesicular positioning at cortical synapses JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.05.895029 DO 10.1101/2020.01.05.895029 A1 Eleonora Vannini A1 Laura Restani A1 Marialaura Dilillo A1 Liam McDonnell A1 Matteo Caleo A1 Vincenzo Marra YR 2020 UL http://biorxiv.org/content/early/2020/01/06/2020.01.05.895029.abstract AB Neuronal networks’ hyperexcitability often results from an unbalance between excitatory and inhibitory neurotransmission; however, underlying synaptic alterations leading to this condition remains poorly understood. Here, we assess synaptic changes in the visual cortex of epileptic tetanus neurotoxin-injected mice. Using an ultrastructural measure of synaptic activity, we quantified functional differences at excitatory and inhibitory synapses. We found homeostatic changes in hyperexcitable networks, expressed as an early onset lengthening of active zones at inhibitory synapses followed by spatial reorganization of recycled vesicles at excitatory synapses. A proteomic analysis of synaptic content revealed an upregulation of Carboxypeptidase E (CPE) following Tetanus NeuroToxin (TeNT) injection. Remarkably, inhibition of CPE rapidly decreased network discharges in vivo. These analyses reveal a complex landscape of homeostatic changes affecting the epileptic synaptic release machinery, differentially at inhibitory and excitatory terminals. Our study unveil homeostatic presynaptic mechanisms which may impact release timing rather than synaptic strength.