Zebrafish embryos are able to survive anoxia for up to 24 hours. We are investigating the mechanisms underlying this remarkable tolerance as they may provide important clues on adaptive mechanisms for conserving brain energy that may have therapeutic relevance. We are using forward and reverse genetic approaches to identify key players in anoxia tolerance.  Candidate genes currently being considered are AMPK and Hif1-alpha. We hypothesize that these and other to-be identified genes confer anoxia tolerance by functioning as switches that are turned by low oxygen/ATP and that decrease brain metabolism by shutting down cellular processes that are energy-demanding.