Mouse Behavioral Testing

Dr. Wahlsten received his Ph.D. degree in psychology from the University of California Irvine and completed his postdoctoral work in behavior genetics at the Institute for Behavioral Genetics at the University of Colorado. He then established research laboratories at the University of Waterloo, the University of Alberta, and the University of North Carolina. The laboratory work involved genetic and developmental analysis of mouse brain defects and methods of behavioral testing. He also acquired expertise in statistical data analysis and theoretical issues central to the field. He was a co-founder of the very successful journal Genes, Brain and Behavior, and was given the Distinguished Scientist award by the International Behavioral and Neural Genetics Society. Throughout his career, he has taught behavioral and neural genetics to undergraduate and graduate students.

PrefaceAcknowledgmentsChapter 1 Introduction to the Research Process The Research Process: Scientific Aspects Adapting the approach to the stage of an investigation Mice, mice, and more mice Measuring instruments: Tests The formal research design Sample size Ethics approval Logistics Obtaining subjects The test day Prelude to data analysis Data analysis Publishing results The Institutional Context of Research People Facilities PoliciesChapter 2 Mice Mice Versus Rats Models of Human Functions Origins of Standard Mouse Strains Kinds of Breeding Schemes Outbred animals Closed colony Inbred strains F1 hybrids Selectively bred lines The Process of Close Inbreeding Inbred Strains for Research Special Genotypes Derived from Inbred Strains Coisogenic strains Congenic strains Consomic strains Conplastic strains Recombinant inbred strains Designer Mice: Transgenic Methods and Targeted MutationsChapter 3 Tests of Mouse Behavior Popularity of Tests Commercial Devices Exploration Open field Nose poke hole board Symmetrical Y maze Home cage activity Anxiety Lightdark box Elevated plus maze Elevated zero and square mazes Vogel conflict test Geller conflict test Motor Function Ataxia observation Grip strength Balance beam Grid test Rotarod Running wheel Treadmill Learning Operant learning Mazes Spatial memory Electric shock Other TestsChapter 4 Designs One Group Two Groups Matched Pairs Repeated Measures Single-Factor Study With More Than Two Groups (One-Way Design) Two-Factor Studies Multi-Factor Studies Specialized Designs Reciprocal hybrid crosses Manipulations of the maternal environment Transgenerational influences Selective breeding with control for environmental influences Complications Fixed and random effects Nested factors Litter as unit Consulting experts Utilities One- and two-factor studies Three- and higher factor studies Breeding listChapter 5 Sample Size Utilities to do the Calculations Population and Sample Two kinds of populations Specifying an entire population Random choice of a sample Comparing two groups Comparing several groups Size of an Effect What is an effect? Index of effect size Effect size for a study with two groups Effect size for more than two groups Finding effect size from published data Significance of an Effect False positives happen The more tests, the higher the risk of a false positive Power of a Test Finding the Correct Sample Size Two independent groups 2 2 design, 4 groups J groups, omnibus test J groups, linear contrast Two-way factorial design Designs with more than two factorsChapter 6 Ethics Approval Good Ethics and Good Science The Era Before Regulation The Era of Regulated Research With Animals Ethical Status of Mice and Rats The Fundamental Ethical Principle of Animal Research The 3Rs Replacement Reduction Refinement Case Studies Death as an end point Food deprivation Categories of Invasiveness and Severity Categories for Behavioral Tests Used with Mice The FutureChapter 7 Logistics The Total Experiment One-factor design Two-, three- and four-factor designs The Principle of Balancing and Randomization The Total Sample Divided into Smaller Units Throughput Partitioning the Work Day The Balancing Act Enumeration Latin square Randomization to the Rescue Shipments, Cages, Tail Marks, and Id Numbers Cages in the Colony Room The Data Sheet Final Consultation Other Examples More Intricate DesignsChapter 8 Getting Ready for Testing Ordering Mice Shipping Unpacking Marking for Individual Identification Housing Group versus individual housing Cage enrichment Lightdark cycle Going to School: Test DayChapter 9 Prelude to Data Analysis Know Your Object Contents of One Row of Data The Id Code Order of Variables Across a Row Naming Variables The Value of Using the Right Values The Plague Called Missing Data Importing the Spreadsheet into the Statistical Program Checking for Errors in the Data The Crucial Distinction Between Errors and Exceptions Looking at Results Statistical Data Analysis as a Final Step in the ProcessChapter 10 Domains and Test Batteries Types of Observations Whole behavior versus criterion response Free expression versus highly constrained actions Microscopic analysis versus the whole picture Short duration versus full day observation The Ethological Method Domains and Subdomains Complexity of Domains Test Batteries Every test changes the mouse Advantages of using different mice for different tests Efficiency and economy of numbers comes at a price Current wisdom about test batteries Testing effects of batteries Effect size and importance of test order effects One solution: Standard test orders How stressful are tests?Chapter 11 Motivating Mice Hunger and Food Deprivation Appetite without deprivation IntelliCage Methods of food deprivation A refined method for daily deprivation Degree of hunger and eating Revised eating test Electric Shock Basic features of a shock source Variables that influence intensity Determining the correct level of shock Threshold of sensation Threshold of overt reaction Kinds of responses and task requirements Water Escape Depth Temperature Number of trials Opacity Cleanliness Air Puff Aversion Parameters of air puffs Determining optimal air flow rate Avoidance of air puffs Motivation and LearningChapter 12 Qualities of Behavioral Tests Resolution, Accuracy, and Precision Consistency Reliability Replicability ValidityChapter 13 Task Refinement and Standardization Flawed Tests and Missteps in the Research Process The lab cat Mouse shuttle avoidance Bar press avoidance Task Complexity The relatively simple open field The submerged platform water escape task Do task parameters matter? Probe trial performance Escape latencies and rate of learning Task Refinement The accelerating rotarod The submerged platform water escape task Prospects for refining other tests Test Standardization Standardizing Lab EnvironmentChapter 14 Video Tracking Basic Features Camera and lens Spectral sensitivity and filters Focus of the lens Hardware Modifications for Video Tracking Solid floors for uniform fields of view Paint in the water tank Eliminating shadows and blind spots The experimenters hand Doubts about the Accuracy of Video Tracking Tracking in Edmonton and Portland VideoScan versus ANY-maze Accuracy and Precision from a Mechanical Device The Solution: Ir Backlighting The True Path LengthChapter 15 The Laboratory Environment Two Sources of Environmental Variance in Test Scores Environmental Effects on Test Scores: Early Studies Interactions with Lab Environment: Recent Studies Complexity of the Lab Environment Standardizing the Lab Environment Heterogenization of the Lab Environment Strategies for Standardizing the Lab EnvironmentAppendixReference ListIndex