Changes in Functional Connectivity in Cultured Neuronal Networks During and After Transient Hypoxia of Varying Depths and Durations

The absence of oxygen in the core of a brain infarct quickly leads to cell death. Remaining but limited perfusion in the penumbra causes energy depletion, and disrupts synaptic transmission. Connectivity loss probably correlates with loss of cognition and restoration of connectivity seems crucial for possible recovery. However, in vivo, connectivity is difficult to assess due to limited access to the neurons and restricted experimental freedom. We studied the effects of hypoxia of varying depth and duration on functional connectivity in cultured neuronal networks on multi-electrode arrays. The first six hours of hypoxia resulted in reduced connectivity, followed by restoration of functional connectivity to baseline values upon re-oxygenation. Under persisting hypoxic conditions, beyond 6 hours some recovery of connectivity occurred, until ~24 hours, when connectivity further declined. In cultures that survived 48 hours of hypoxia, strength of persisting connections tended to remain around baseline values, but the number of remaining connections was significantly lower. The probability that a certain connection survived hypoxia was uncorrelated to its baseline strength. Still, even during hypoxia, new connections were formed. This occurred at a rate seemingly independent of the hypoxic conditions. On average, the loss of baseline connections exceeded the formation of new ones during hypoxia.