Abstract
Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. Current labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescent indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended time scales. We report on a dual-mode high-density microelectrode array, which can simultaneously record in (i) full-frame mode with 19,584 recording sites and (ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we develop reliable analysis tools, which drastically increase the throughput to infer axonal morphology and conduction speed.
Highlights
Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function
By combining the two recording modes, full-frame active pixel sensor (APS) and high-signal-to-noise ratios (SNRs) switch-matrix (SM) mode, the dual-mode MEA (DM-MEA) can significantly enhance the characterization of extracellular signals of neurogenic cells
We presented a highly versatile DM-MEA for live-cell analysis of neurogenic cells and demonstrated its applicability for the functional characterization of neuronal preparations at subcellular, single-cell and network levels
Summary
Chronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. An approach for comprehensive functional characterization of neuronal cultures is still lacking, as it requires a high-throughput method with high spatial-temporal resolution to capture neuronal features at subcellular, single-cell, and network levels. Live-cell functional imaging should be (2) highly sensitive and offer sufficient spatiotemporal resolution to detect biologically relevant details that unfold over days and weeks It should allow for (3) reliable data acquisition and (4) feature extraction that ensure high reproducibility of the results. Fullframe architectures with so-called active-pixel-sensors (APSs)[20,21,22,23], enable simultaneous recording from every electrode of the array, but are limited by relatively low signal-to-noise ratios (SNRs) caused by circuit-design constraints, i.e., the little available area in a pixel to realize high-performance circuits.
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