Thermoplasmonics and hydrogel-based neural chip platform for manipulation of structure and function of neuronal networks

Abstract

Cultured neuronal networks have been widely studied as an in vitro model system to explore the relationship between network structure and function. To design networks with a controlled structure, various cell patterning methods were developed to regulate neuron adhesion and neurite outgrowth. However, most of the techniques lack the ability to control network structures after cell cultivation, making it difficult to assess functional changes by specific structural alterations. In this dissertation, I present a neural chip platform for manipulation of structure and function of neuronal networks during cell cultivation. First, a technological platform based on gold-nanorod-mediated thermoplasmonics, micropatterning with thermosensitive agarose hydrogel, and neural recording using a microelectrode array was constructed. The developed platform could successfully induce new neurite outgrowths or eliminate interconnecting neurites in mature neuronal networks. Second, functional changes of neuronal networks by structural alteration were analyzed. The emergence of synchronization or desynchronization between networks derived from the creation or removal of neurite connections was confirmed. Third, network activity was modulated through thermoplasmonic neural inhibition technique to estimate functional connectivity of networks. Based on activity suppression of networks, functional influence between the connected networks was evaluated. Fourth, the developed platform was applied to assays of neurite outgrowth and synaptogenesis. By utilizing the advantage of the platform that neurite guidance and connection could be induced at the desired time points, the development-dependent characteristics of cultured neurons were investigated. Taken together, the neural chip platform developed in this dissertation is expected to be useful for studying structure-function relationship and neural development of neuronal networks.