Calcium dynamics of living neural networks under modulated brain metabolic stresses

Information processing in living neural networks (LNNs) varies greatly across numerous biological conditions and parameters. For instance, brain metabolic stress from conditions such as excess Reactive Oxygen Species (ROS), hyperglycemia, and hypoglycemia has been implicated in impaired cognitive function and neurodegenerative diseases. However, ROS is also a crucial second messenger with impacts on cellular maturation and learning, and local glucose demand varies strongly with dynamic neural activity. Methods to modulate and record ROS and glucose levels will enable studies on their impact on information processing in LNNs. We develop photobiomodulation (PBM) with high-UV (370 nm) light as an effective means to dynamically increase local ROS levels in human neural progenitor cell (hNPC) cultures. The photoinduction of ROS selectively impacts ROS levels in the illuminated cells and increases basal levels of calcium. However, this basal increase did not impact spontaneous calcium signaling. We also study the calcium activity of the hNPCs under constrained and abundant glucose concentrations during spontaneous and driven activity. With titration, we benchmark glucose consumption both during culture maturation and after experiments. By estimating glucose consumption, we characterize both energy-dependent calcium dynamics and a potential confound for long-duration, high-activity in vitro experiments.