Lubrano, Claudia (2022) Interactive Biohybrid Synapses. [Tesi di dottorato]

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Synaptic plasticity is at the base of learning and memory capabilities of the human brain and lately recent studies reported a strong correlation between synaptic dysfunction and neurodegenerative diseases. Unfortunately, the complexity of the brain and the nervous system prevents the investigation of mechanisms underlying cognitive impairment, and for this reason the possibility to inhibit neurodegeneration at the early stage of disease is still far from being concrete. The impossibility to study neuronal cells in their native environment pushed the neuroelectronic field towards the implementation of biomimetic in vitro platforms which could resemble the main features of biological synapses, like geometrical shape, structure and functionalities. At this purpose, in recent years supported lipid bilayers and 3D patterned electrodes emerged as promising strategies to mimic neuronal membrane composition and dendritic spines shapes. Additionally, the advent of neuromorphic devices based on conductive polymers provided artificial synapses exhibiting short and long-term plasticity, while being able to transduce biological ionic signals into electrical currents. In this thesis, we present the implementation of biohybrid biomimetic synapses which could pave the way for a new class of adaptable in vitro platforms able to trick cells to recognize electronic devices as part of their native environment. The first part of the project was focused on engineering a biohybrid synapse where a PEDOT:PSS-based OECT acts as artificial post-synaptic neuron while cells directly interfaced with the device represent the biological pre-synaptic end. Of note, the OECT conductance can be modulated by the oxidation of dopamine directly secreted from cells, demonstrating neurotransmitter-mediated short and long-term plasticity. In the second part of the project, the OECT was coupled with a synthetic phospholipid bilayer to implement an artificial synapse with biomimetic features. Finally, the role of the biomembrane on the short-term plasticity of the OECT was evaluated varying also the position of the gate electrode in respect to the neuromorphic channel. Here, the SLB behaving as an ionic barrier amplifies the short-term potentiation of the artificial synapse, especially when the top gate electrode forces ions to cross the double layer. In light of the results presented in this thesis, biomembrane-based organic neuromorphic transistor could represent a first step towards the implementation of fully biomimetic in vitro systems, which resemble composition and functionalities of neuronal networks and as such, could contribute to unwind the complex mechanisms underlying neurodegeneration and synaptic plasticity loss.

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