The project's idea stands on two main pillars: (i) the ability of focal subretinal microperfusion of glutamate to elicit retinal ganglion cells network-mediated responses in a blind rodent model; (ii) the ability of hollow plasmonic nanochannels to enhance electromagnetic radiations and directly interact with neurons in the size range of synaptic clefts. HyVIS will combine these two concepts to interface the retinal bipolar cells (BCs) with a plasmonic nanochannel filled with smart polymers able to release glutamate in response to optical stimuli, mimicking neurotransmitter release sites on presynaptic terminals. Inspired by the natural making of a synapse, we will induce the postsynaptic specialization in the denervated BC by single-cell virus stamping, thereby sealing the synaptic connection. The molecular mechanisms that regulate wiring specificity and synaptic diversity in the vertebrate brain rely on “individual identification tags” on pre- and postsynaptic cells that allow neurons to distinguish one another and selectively connect by “specific chemical affinities”. Both presynaptic adhesion molecules coating the nanochannels and viruses stamping will induce the denervated BC to express the cognate postsynaptic adhesion partner and ionotropic glutamate receptors to re-create the secluded synaptic cleft efficient in glutamate signal transduction.
HyVIS is a research project funded from the European Union’s Horizon 2020 research and innovation actions (RIA) scheme under grant agreement no. 964468.