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Genetic analysis of behavior

Genetic analysis of behavior. February 24 th , 2010 Part I. Overview. Part I Animal behavior example Levels of analysis of behavior Gene-environment interactions Methods of Behavioral Genetics Classical Methods Molecular Methods Examples of single gene mutations (loss) on behavior.

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Genetic analysis of behavior

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  1. Genetic analysis of behavior February 24th, 2010 Part I

  2. Overview Part I • Animal behavior example • Levels of analysis of behavior • Gene-environment interactions • Methods of Behavioral Genetics • Classical Methods • Molecular Methods • Examples of single gene mutations (loss) on behavior

  3. Overview Part II • Zebrafish visual system • Visually-mediated behaviors in the zebrafish (and electrophysiology) • Identifying genes essential for visual behavior • Examples • The zebrafish nrc mutant • Photoreceptor development in the rainbow trout

  4. Examples of specific behaviors in animals

  5. The monogamous prairie vole • Mammal, found in United States in Canada • In contrast to other voles the prairie vole • is monogamous What is the basis of this behavior?

  6. What causes its monogamy? Neural basis Genetic basis Environmental basis Increased expression of Vasopression receptors (V1a) in brain Positive feedback mechanism avpr1a encodes for V1a receptor Difference in promoter region in prairie Voles Transgenic animal, over-expressing avpr1a in VP leads to increased bonding with the partner Reproductive benefits of mating with only one partner Mate-guarding males might have had more offspring that polygynous males under specific conditions

  7. Levels of analysing animal behavior

  8. What is Behavioral Genetics? GENES ENVIRONMENT “Nature” versus “Nurture” Aim of Behavioral Genetics – Studying the influence of genes on behavior

  9. Shoaling Behavior in Zebrafish Our results demonstrate that larval zebrafish shoal early in their development, but do not exhibit a shoaling preference until they are juveniles. Moreover, we find that the shoaling preference is stable, as changing the social environment of fish after they had acquired a preference did not change their preference. Raymond et al., Animal Behavior 2007

  10. Food preferences of garter snakes • coastal snakes – love banana slugs • inland snakes – primarily feed on fish and frogs • Does this difference have a hereditary basis? • - isolate offspring of two populations • Present offspring with diet (banana slugs) • - crossing experiment – phenotypic variation in the • resulting offspring

  11. More examples of links between genes and behavior • Mutation in the Shaker gene in Drosophila – flies shake violently under anesthesia = mutation in potassium channel structural protein • Physical and behavioral changes in puberty – steroid hormones induce expression of genes in cells having receptors specific for these hormones (such receptors are most concentrated in brain regions known to be essential for the control of sexual behavior) • Birdsong: young zebrafish imitate the songs of adult males; the expression levels of the zenk gene is increased greatly when young birds are exposed to songs of their own species males Normalized density of zenk mRNA Mello et al., Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6818-22

  12. Methods of studying the influence of genes on behavior • “Classical” techniques • Molecular techniques

  13. Classical experimental methods to demonstrate the influence of genes on behavior • INBREEDING • ARTIFICIAL SELECTION • HYBRIDIZATION

  14. INBREEDING • Mating of brothers and sisters to hold genetic input constant • Genetic effects on behavior can be separated from environmental effects, as the resulting strains are virtually genetically identical • Example for genetic trait: coat color in mice after about 20 generations of inbreeding offspring will be 98% identical http://blogs.knoxnews.com/knx/munger/miceblog.jpg

  15. Showing the role of Genes difference in genetic background - different behavior Example: Antipredator behavior in paradise fish Showing the role of the environment difference in environment – different behavior Example: Cross-fostering of prairie/ meadow voles Prairie voles show more parental care than meadow voles. Is that difference due to genes or early experience? Cross-fostering showed that meadow voles fostered to prairie voles showed higher parental care than those raised by meadow vole parents Comparison of inbred strains Miklosi et al., Behav Genet. 1997 May;27(3):191-200.

  16. ARTIFICIAL SELECTION If the frequency of a trait can be altered by choosing the appropriate breeders,it must have a genetic basis. Example: Artifical selection for nesting behavior in house mice Lynch, Genetics. 1980 Nov;96(3):757-65.

  17. HYBRIDIZATION Mating of two individuals displaying a particular type of behavior in distinct but different ways; behavior of offspring is observed Example: Feeding behavior of Drosophila larvae „Rover“ larvae: move around continually on their food „Sitter“ larvae: travel only short distances Crossbreeding experiments showed that the trait is controlled by one gene and that rover is dominant to sitter. Sokolowski Nature Reviews Genetics 2, 879-890

  18. Genetic engineering • Recombinant DNA technology • Loss of function Inactivation of genes (knock-out, knock-down) • Gain of function Overexpression of genes • Transgenes Expression studies, GFP fusion proteins,...

  19. Forward genetic approach Phenotype Genotype Zebrafish impaired in any aspect of visual system function Mutated gene responsible for the impairment

  20. Reverse genetic approach Genotype Phenotype Knock-down of gene of interest implicated in any aspect of visual system function Zebrafish impaired in this specific aspect of visual system function

  21. Examples of single gene mutations affecting behavior • Mutant (forward genetics) • Knock-out/Knock-down (reverse genetics)

  22. dunce deficiency rutabaga deficiency ATP Adenylyl-cyclase cAMP cAMP phosphodiesterase 5`AMP binds to and activates PKA (protein kinase A) activates CREB gene CREB protein turns on genes that cause changes in the structure and function of nerve cells that underlay memory Example: Drosophila dunce mutant • Mutations can be induced by mutagenic chemicals or irradiation • Mutant animals can be screened for impairments of a specific behavior • Example: Drosophila dunce mutant • Isolated by screening a mutagenized Drosophila population on the basis of their olfactory learning behavior • dunce mutants fail to learn to avoid odors associated with a shock, however they are able to detect both • If dunce flies are shocked in the presence of an odor without being exposed to a second odor, they will avoid this odor, but • this association fades quickly – early stage of memory formation is defective • dunce codes for an enzyme called cAMP phosphodiesterase • second mutant rutabaga has similar phenotype

  23. Example: Zebrafish mutants with altered nicotine response Petzold A M et al. PNAS 2009;106:18662-18667

  24. Creation of a knock-out mouse http://141.217.91.198/genereplacement.GIF

  25. Example: Mouse model for conflict resolution Understanding how emotion is generated, how conflicting emotionsare regulated, and how emotional states relate to sophisticatedbehaviors is a crucial challenge in brain research. Model animalsshowing selective emotion-related phenotypes are highly usefulfor examining these issues. Here, we describe a novel mousemodel that withdraws in approach-avoidance conflicts. X11-like(X11L)/Mint2 is a neuronal adapter protein with multiple protein-proteininteraction domains that interacts with several proteins involvedin modulating neuronal activity. X11L-KO mice are subordinated in competitive feeding conditions Social interaction against an intruder is significantly decreased in X11L-KO mice Marble burying are impaired in X11L-KO mice Sano et al. J NeuroSci 2009

  26. Example: Transgenic mouse overexpressing NMDA receptor Transgenic mice perform better than their wildtype littermates in the hidden-platform water test Tang et al., Nature. 1999 Sep 2;401(6748):63-9.

  27. AUG mRNA of gene of interest 1-cell stage Morpholino approach to create zebrafish morphants X Translation to protein Morpholino oligonucleotide Injection of optimal concentration of the morpholino (only transient knock-down)

  28. Knock-down of zebrafish pink1 results in locomotor deficits Mutations in the human PTEN-induced kinase 1 (PINK1) gene are linked to recessive familial Parkinson's disease Xi et al., EJN 2010

  29. Knock-down of zebrafish pink1 results in locomotor deficits Xi et al., EJN 2010

  30. Literature • Textbooks: • Animal Behavior (John Alcock) • Perspectives on Animal Behavior (Goodenough, McGuire, Wallace) • Articles: • Raymond et al., Anim Behav. 2007 November; 74(5): 1269–1275 • Petzold A M et al. PNAS 2009;106:18662-18667 • Xi et al., European Journal of Neuroscience, Vol. 31, Issue 4, Pages 623-633 • Sano et al., The Journal of Neuroscience, May 6, 2009, 29(18):5884-5896

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