Synaptome and Synaptopathies

The research is focused on the role of presynaptic proteins in the definition of the functional properties of central synapses. Several mutations in presynaptic and extracellular matrix proteins are associated with epilepsy and ASD. Autism has a complex genetic architecture, and a major question is how alterations in these many genes translate into similar behavioral phenotypes. We study the effects of downregulation and overexpression of an array of pathogenic candidates, including synapsins (Farisello et al., 2013; Medrihan et al., 2013; Michetti et al., 2017; Gerth et al., 2017), calcium channels (Thalhammer et al., 2017), PRRT2 (Valente et al., 2016; Valtorta et al., 2016; Michetti et al., 2017; Valente et al.,  2018) TBC1D24 (Falace et al.,  2014; Tagliatti et al., 2016), vATPase (Fassio et al., 2018), APache (Piccini et al., 2017), Kidins220 (Cesca et al., 2015; Fiala et al., 2015) to uncover their physiological role in synaptic transmission, excitation/inhibition balance and network activity. We aim at identifying new therapeutic targets and developing treatments for 'opening a window' of persistent structural normalization of neural circuitries. To this end, we employ electrophysiological recordings coupled with optogenetics and electron microscopy in brain slices and primary neuronal cultures, behavioral analysis in constitutive and conditional knockout mice, as well as apply viral-mediated rescue strategies.

People: Benfenati, Cesca, Cingolani, Maragliano