Investigation of neuroplasticity mechanisms of in vitro neural networks

The past decade has seen increasingly rapid advances in the field of in vitro neural network modeling using human induced pluripotent stem cell (hiPSC) derived neural progenitor cells. These cells have the ability to differentiate into specific neuron types and afford the opportunity to study complex neural systems in a reductionist paradigm, using state of the art techniques such as multielectrode arrays (MEA) and microfluidic devices. In addition, by incorporating optogenetic, as well as chemogenetic tools such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), intrinsic mechanisms of network plasticity processes can be modulated and studied. While neural networks and plasticity have been intensively studied, the generalisability of much published literature on fundamental properties of neural development remains problematic. This leaves much to be elucidated on observed events such as spontaneous synchronous network firing and burst patterns, as well as the connections spontaneously formed throughout the network. This project aims to: - Monitor the development of cortical neurons differentiated from hiPSC-derived stem cells over a period of time and identify key aspects of network maturity - Study the properties of emerging electrophysiological activity and self-organization - Provide novel insights into intrinsic processes of synaptic plasticity mechanisms involving both Hebbian and homeostatic plasticity - Understand network response to induced perturbations through electrical, optogenetic and chemogenetic stimulations. - Determine mechanistic causes of disease in perturbed neural systems as reflected in their altered connectomes. The overarching hypothesis is that in vitro neural systems self-organize and develop electrophysiological properties akin to those found in vivo, and through direct modulation, network activity can be influenced towards malfunction or adaptive learning states.