Behavioral Neurobiology of Drosophila Dr. E. Axel Gorostiza Brno, 17.03.2015 A little bit of history. Charles W. Woodworth (USA) Entomologist (April 28, 1865 – November 19, 1940) William Ernest Castle (USA) Embryologist and geneticist (October 25, 1867 – June 3, 1962) Thomas Hunt Morgan (USA) evolutionary biologist, geneticist and embryologist (September 25, 1866 – December 4, 1945) The Nobel Prize in Physiology or Medicine 1933 was awarded to Thomas H. Morgan "for his discoveries concerning the role played by the chromosome in heredity". Why Drosophila? http://drosophiladrawings.blogspot.de/ http://www.theflyroom.com/ But, what about behavior? The American Naturalist, Mar., 1905, pp. 157-171 J. Exptl. Zool., 1918, 49–106. Seymour Benzer Physicist, molecular biologist and behavioral geneticist (October 15, 1921 – November 30, 2007) The father of Neurogenetics Jerry Hirsch Behavioral geneticist (September 20, 1922 – May 3, 2008) period perlong pershort per0 Drosophila as a model for neurodegenerative diseases Drosophila as a model for neurodegenerative diseases 1) To model human diseases. 3) To find modulators, interacting genes or treatments related to diseases. 2) To find genes involved in neurodegeneration or diseases. Again, why Drosophila? Again, why Drosophila? L1: 3 million synapses estimated 100000 neurons Shafer OT, Taghert PH, PLoS ONE, 2009 L1: 10000 neurons http://albert.rierol.net/lab.html Schmidt I. et al, The Journal of Neuroscience, 2012 Metamorphosis: new body, new neurons, new behaviors André Klarsfeld et al., The Journal of Neuroscience 2011 C. Helfrich-Förster et al., The Journal of Comparative Neurology 2007 Drosophila’s toolbox Genetic tools: balancers fruitless  Sex determination  Development structures necessary for courtship: o Muscle development o Neurons  Aggressive behavior  Male courtship behavior: o wing vibration o song production o mating o etc.  etc. Genetic tools: balancers Genetic tools: balancers Genetic tools: transgenic flies Koen J. T. et al, Development 2007 Drosophila transgenesis: white+ transgene DNA (red) is injected into generation zero Drosophila embryos (G0) of less than 1 hour old, which have been obtained from a parental (P) generation. Genetic tools: transgenic flies Demir E. & Dickson B, Cell 2005 Genetic tools: GAL4/UAS and other tools Genetic tools: GAL4/UAS and other tools Test 32°C 19°C Neuronal inhibition and activation Genetic tools: GAL4/UAS and other tools GAL4 collection + UAS-dTrpA1 Genetic tools: GAL4/UAS and other tools Genetic tools: GAL4/UAS and other tools Genetic tools: GAL4/UAS and other tools Optogenetics: Channelrodopsin & others UAS-ChR2 UAS-ReaChR UAS-Chrimson UAS-Chronos Proboscis extension reflex sugar-sensing gustatory receptor neurons (GRNs) Genetic tools: GAL4/UAS and other tools Genetic tools: GAL4/UAS and other tools Calcium activity sensors: GCaMP Chiappe M.E. et al, Current Biology 2010 Behavioral paradigms Behavioral paradigms: Taxis Phototaxis Geotaxis Behavioral paradigms: geotaxis Behavioral paradigms: phototaxis Otsuna H. et al, Front. Neural Circuits, 2014 Behavioral paradigms: phototaxis Single fly assay Population assay Behavioral paradigms: phototaxis Behavioral paradigms: circadian rhythms & sleep Ozgur Tataroglu & Patrick Emery, Methods, 2014, 140 - 150 Behavioral paradigms: circadian rhythms & sleep Behavioral paradigms: gap Motor coordination Goal-directed actions Behavioral paradigms: courtship Behavioral paradigms: aggression Tachykinin-expressing neurons Behavioral paradigms: Buridan Behavioral paradigms: Buridan Colomb J and Brembs B, F1000Research 2014 Behavioral paradigms: detour & visual place learning Behavioral paradigms: olfactory learning Behavioral paradigms: visual learning Behavioral paradigms: flight simulator Brembs, B & Heisenberg, M., J Exp Biol 2001 Thank you!