(Keynote) Biologically Targeted Janus Synapse between Ultramicroelectrode and Primary Neuron

Seamless neural interfaces conjoining neurons and electrochemical devices hold great potential for highly efficient signal transmission across neuronal systems and the external world. Signal transmission through chemical sensing and stimulation via electrochemistry is remarkable because communication occurs through the same chemical language of neurons. One promising approach is a synaptogenesis-involving method, which offers an opportunity for synaptic signaling between these systems. Janus synapses, one type of synaptic interface utilizing synaptic cell adhesion molecules for biotic-abiotic interface construction, possess unique features that enable the determination of location, direction of signal flow, and types of neurotransmitters involved, promoting directional and multifaceted communication. Such unique synaptic interfaces can directly exchange signals to and from neurons, in a similar manner to that of natural chemical synapses. In this talk, I summarize developments to improve the interface between neurons and electrodes by targeting neurons or sub-neuronal regions including synapses. Furthermore, recent progress in electrochemical neurosensing and iontronics-based chemical delivery made by my group is introduced. It includes the first successful establishment of Janus synapses between primary dopaminergic (DA) neurons and abiotic substrates using a neuroligin-2 (NLG2)-mediated synapse-inducing method. NLG2 immobilized on gold-coated microspheres can induce synaptogenesis upon contact with spatially isolated DA axons. The induced DA Janus synapses exhibit stable synaptic activities comparable to that of native synapses over time, suggesting their suitability for application in neural interfaces. By calling for DA presynaptic organizations, the NLG2-immobilized abiotic substrate is a promising tool for on-site detection of synaptic dopamine release. References Cho, W.; Jung, M.; Yoon, S. -h.; Jeon, J.; Oh, M. -A.; Kim, J. Y.; Park, M.; Kang, C. M.; Chung, T. D., On-Site Formation of Functional Dopaminergic Presynaptic Terminals on Neuroligin-2 Modified Gold-Coated Microspheres, ACS Appl. Mater. Interfaces , 2024 , 16 ( 3 ), 3082-3092. Cho, W.; Yoon, S. -h.; Chung, T. D., Streamlining the interface between electronics and neural systems for bidirectional electrochemical communication, Chem. Sci ., 2023 , 14 , 4463-4479. Han, S. H.; Kim, S. I.; Oh, M. -A.; Chung, T. D., Iontronic analog of synaptic plasticity: Hydrogel-based ionic diode with chemic