We propose to use the in vitro brain slice technique with cortical and medullary-based (cerebellar) neuronal networks, to unravel adaptive neuronal mechanisms to hypoxia in higher vertebrates. In this context, we will also investigate the possible role of the respiratory pigment neuroglobin in this respect. We will use diving animals (seals and ducks) which in their everyday life are frequently asphyxiated, and compare their hypoxic responses with those of non-diving controls (mice and domestic chicks), t o reveal the specific, neuronal mechanisms that allow brains of diving animals to survive hypoxic conditions that would be detrimental to any human brain. Brain slice preparations of functionally intact networks combine the unique advantage of being both accessible to a rigorous cellular analysis and amenable to a systems-level analysis, and the technique is generally accepted in studies of general principles of brain functions/malfunctions that underlie various disease states. The proposed research combi nes the forces of leading laboratories in a) comparative integrative physiological research (Blix and Folkow), b) the brain slice preparation technique (Ramirez), and c) the investigation of the occurrence, distribution and physiological role of neuroglob in (Burmester, Hankeln and Brix), and we expect that the insights gained using this novel approach may be of direct relevance for developing new strategies to make the mammalian brain more tolerant to hypoxia.