Engineering neuronal networks with nanomaterials: graphene shaping of synaptic activity

Graphene is a single atomic plane material consisting of sp2 -hybridized carbon atoms with a hexagonal structural organization and characterized by unique properties such as high electrical conductivity, mechanical flexibility and optical transparency. Due to their peculiar features, graphene and its derivates have attracted an increasing interest for biomedical applications including drug and gene delivery, imaging and diagnostic or tissue engineering. However, using graphene-based nanomaterials (GBNs) in modern medicine, in particular neurology, needs a greater and deeper understanding of the cell-nanomaterial interactions. In this framework we focus on studying the impact of GBNs on the neuronal network and their ability in shaping synaptic transmission. First, we exploited 3D elastomeric scaffolds enriched with graphene to better understand the effects of this nanomaterial on the neural activity when interfacing neurons and synapses in the third dimension. Our results, using imaging techniques, show the ability of graphene to modulate the neuronal network formation in a 3D environment which might be due to modulations in the excitatory/inhibitory ratio. Afterwards we investigated the interactions between graphene oxide flakes with small lateral size (s-GO) and isolated amygdala neurons and synapses. Thus, we developed and characterized an in vitro model of amygdala network using immunofluorescence and electrophysiological techniques. When we acutely applied s-GO to these cultures, the nanomaterial was capable to selectively alter the glutamatergic excitatory activity. This peculiar interaction may be taken into account for exploiting s-GO as a novel tool to target central nervous system (CNS) synapses.