Optogenetic modulation of stress signaling - towards a new animal model for depression

• Antragstellerin: Professorin Soojin Ryu, Ph.D.
• Fachliche Zuordnung: Biophysik
• Förderung: Förderung von 2010 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 119438981

Light-gated/actuated channels and enzymes provide a unique opportunity to noninvasively and precisely control cellular responses. The usage of “Light-switch” proteins to investigate complex animal physiology and behavior is an exciting field, which is just beginning. The zebrafish offers an attractive system for optogenetic analysis of vertebrate behavior and physiology due to its genetically amenable and transparent embryos. However, the zebrafish system has been under-explored so far with only two publications reporting the usage of optogenetic tools. Therefore a major goal of this proposal is to expand the toolbox of light-switches for the usage in zebrafish. We will implement and test the functionality of several novel light-switches generated by members of FOR. The second aim of the proposal is to use these optogenetic tools to control neuroendocrine responses in zebrafish. A focus will be the complex adaptive hormonal response of an animal to environmental stimuli that threaten homeostasis, called the stress response. The stress response is critical for the survival of an animal and malfunctioning of the stress response system is implicated in a number of human diseases including anxiety and depression. By implementing new light switches including Channelrhodopsin variants with different color tuning, photo-activated adenylate cyclase (PAC) and light-actuated glutamate receptors (GluRs), we will generate animals where the stress response can be precisely controlled by light. These animal models will provide hitherto unprecedented opportunities to investigate the effects of chronic stress.

• DFG-Verfahren: Forschungsgruppen
• Teilprojekt zu: FOR 1279: "Protein-based Photoswitches" as optogenetic tools