Mouse Behavioral Testing

  • ID: 1768446
  • Book
  • 304 Pages
  • Elsevier Science and Technology
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Mouse Behavioral Testing: How to Use Mice in Behavioral Neuroscience provides detailed explanations of how to conduct an experiment on mouse behavior from the initial planning of the research design through every step of the process until the data analysis phase.

The book discusses the practical matters that need to be considered carefully when working with any species of animal, such as how many animals need to be tested. It describes the tests and techniques devised specifically for work with mice. Every step of the research process is illustrated with real situations encountered in previous studies. All examples are based on real experiments, and extensive details of several published experiments are provided. The essential features of a behavioral test protocol are outlined, and several complete protocols are provided. Methods to balance the order of tests and determine throughput are described, then a completely balanced order of tests in a complex experiment is presented.

The book will be useful for those already familiar with the general principles of research but are new to the realm of behavioral testing of live mice. It will also serve as a text for a formal course, most likely at the graduate level.

  • A guide to running a behavioral testing lab, including the many aspects of mouse research beyond the confines of the specific test
  • Diagrams and photographs are shown for many kinds of apparatus and test situations with sufficient details such as dimensions to enable building of replicas
  • Provides step-by-step instructions on planning and executing behavioral experiments in order to run them successfully

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Preface

Acknowledgments


Chapter 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


Policies


Chapter 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 Mutations


Chapter 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 Tests


Chapter 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 list


Chapter 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 factors


Chapter 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 Future


Chapter 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 Designs


Chapter 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 Day


Chapter 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 Process


Chapter 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 Learning


Chapter 12 Qualities of Behavioral Tests


Resolution, Accuracy, and Precision


Consistency


Reliability


Replicability


Validity


Chapter 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 Environment


Chapter 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 Length


Chapter 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 Environment


Appendix


Reference List


Index


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Wahlsten, Douglas
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.
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