Multidimensional large-scale, high-density in vitro recording facility for the investigation of neural systems function

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Neural function in our central nervous system arises from complex interactions between different neuronal types within vast neural networks. To understand how these networks operate, simultaneous recordings from large neuronal populations are essential. This can be achieved ex vivo (for example in brain slices) using either imaging (to visualise fluorescent markers expressed in various cell types), or arrays of electrodes (multielectrode arrays; MEAs) that record electrical activity simultaneously from hundreds to thousands of neurons that are functionally connected to each other (or combining both approaches). When using brain slices, surface cells are damaged because of the slicing process that disrupts the integrity of their cellular processes. For that reason, these recordings are normally done in the depth of the tissue with penetrating electrodes or with optical recordings.Traditional MEAs consist of planar electrodes that can record only from the surface of the tissue. They are useful to record from cells in dissociated cultures, growing on the electrodes, or from the isolated retina, where the output cells form a single superficial layer. But these planar MEAs are not amenable to record from brain slices. Most MEA systems currently on the market with penetrating electrodes are too large for delicate isolated neural tissue, and they are limited to having no more than 100 electrodes, which is insufficient to analyse the network dynamics that we aim to study in the related projects we propose..With this proposal, we aim to establish a facility around a unique next-generation MEA system consisting of 4,096 densely packed electrodes, allowing recordings spaced at similar distance to that between adjacent neurones in neural networks. These electrodes consist of pillars that penetrate the tissue and can therefore record neural activity in depth, where cells are not damaged and neural networks are intact. We will combine this cutting-edge new recording system with a fluorescent microscope that will allow us to perform concurrent imaging of various physiological parameters while neurons signal to each other.This novel platform will allow us to study neural function in health and disease at macroscopic scale in health and disease using brain slices, retinas (from rodents and human tissue) and human stem-cell-derived artificial organs (retina, inner-ear).We expect that this new facility will attract exciting new collaborations and technology developments in Newcastle.