dr. joseph garnerlibrary01.forbiddenmousecity.com/l007.pdf · mouse behavior charles river europe,...

Mouse BehaviorCharles River Europe, 2008

Dr. Joseph [email protected]

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Normal mouse behavior:Normal mouse behavior:

Dr. Joseph Garner

Purdue University,Department of Animal Sciences

What is it, and why What is it, and why should we care?should we care?

Physiology alone can only cope with a Physiology alone can only cope with a narrow range of environments narrow range of environments

•• ComfortComfort–– No additional resources No additional resources

required to maintain required to maintain homeostasishomeostasis

•• StressStress–– Resources must be spent to Resources must be spent to

maintain homeostasismaintain homeostasis

•• DistressDistress–– No spare resourcesNo spare resources–– Biological functions are Biological functions are

compromised to maintain compromised to maintain homeostasishomeostasis

•• DeathDeath

••At best, how we house miceAt best, how we house mice



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Behavior makes inhospitable environments Behavior makes inhospitable environments tolerable, or even comfortable. As a resulttolerable, or even comfortable. As a result……

•• The animalThe animal’’s perception s perception of controllability is as of controllability is as influential as the stressorinfluential as the stressor

•• Which compounds issuesWhich compounds issues–– Animals are not omniscientAnimals are not omniscient–– Housing conditions are Housing conditions are

inherently uncontrollableinherently uncontrollable

•• Behaviors often need Behaviors often need substrates substrates –– EnrichmentsEnrichments

•• ‘‘PseudoenrichmentsPseudoenrichments’’, , which donwhich don’’t meet these t meet these needs, are of no benefitneeds, are of no benefit

From a mouseFrom a mouse’’s point of view: s point of view: performance, not engineering standards performance, not engineering standards

•• Without an understanding of mouse biology and Without an understanding of mouse biology and behavior, we make anthropocentric, convenient behavior, we make anthropocentric, convenient decisions, to the detriment of scientific meaning decisions, to the detriment of scientific meaning (validity) and animal welfare(validity) and animal welfare

•• Husbandry and housingHusbandry and housing–– E.g. Cage design, Room temperature, Ventilated racks, E.g. Cage design, Room temperature, Ventilated racks,

EnrichmentEnrichment–– Are we managing what matters, or what is convenient?Are we managing what matters, or what is convenient?

•• Behavioral phenotypingBehavioral phenotyping–– E.g. Morris water maze E.g. Morris water maze –– Are we measuring what matters, or what is convenient?Are we measuring what matters, or what is convenient?

•• Experimental designExperimental design–– E.g. E.g. ‘‘StandardizedStandardized’’ designsdesigns–– Are we controlling what matters, or what is convenient?Are we controlling what matters, or what is convenient?



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OutlineOutline

•• Theoretical conceptsTheoretical concepts•• Sensory world, life history, and normal Sensory world, life history, and normal

behaviorbehavior of miceof mice

•• Abnormal Abnormal behaviorbehavior

•• From a mouseFrom a mouse’’s point of views point of view

Stress and Distress (Moberg 2000)Stress and Distress (Moberg 2000)Example: Mouse thermoregulationExample: Mouse thermoregulation

•• But behaviorBut behavior……

•• Rodents select Rodents select temperatures temperatures depending ondepending on–– Time of day, Time of day,

reproductive cycle, reproductive cycle, activity, fever, group activity, fever, group size, diet, fur thickness, size, diet, fur thickness, acclimatizationacclimatization

•• They huddleThey huddle

•• They adjust nesting They adjust nesting behaviorbehavior

Physiological zones of stress and distressThermoneutral zone: 26-34ºCStress: 18-26ºC, Metabolism increased Distress: <18ºC, Growth rate compromised

Figure from Gordon 1993



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Nest quality and Cage temperatureNest quality and Cage temperature

•• Nest quality Nest quality increases as increases as temperature temperature decreasesdecreases

•• Effect is lost if Effect is lost if mice can mice can choose choose (move) to (move) to other other temperaturestemperatures

Temperature (C)20 25 30

Nes

t Sco

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0

1

2

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No choiceChoice*

The Importance of BehaviorThe Importance of Behavior

•• Under laboratory conditions, Under laboratory conditions, mice become hypothermic in mice become hypothermic in 1212--26 minutes at 26 minutes at --4040ººCC

•• Yet mice can live in meat Yet mice can live in meat freezers at the same freezers at the same temperaturestemperatures…… due to nestsdue to nests

•• Thus the temperature of Thus the temperature of distress, depends entirely on distress, depends entirely on the animals perception of its the animals perception of its ability to control itability to control it



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Impact of prediction and control Impact of prediction and control (Weiss 1970)(Weiss 1970)

•• However it is actually However it is actually the animalthe animal’’s s PERCEPTIONPERCEPTION of its of its ability to predict, ability to predict, control, and correct a control, and correct a stressor that stressor that ultimately determines ultimately determines its physiological its physiological impactimpact

•• This is a key point of This is a key point of MobergMoberg’’s arguments argument

Consequences Consequences –– impaired wellimpaired well--being being impairs scienceimpairs science

•• Controllability & predictability Controllability & predictability ultimately determine behavioral, ultimately determine behavioral, immunological, neuroendocrine immunological, neuroendocrine and autonomic stress responses. and autonomic stress responses. –– Stimulation of lymphocyte Stimulation of lymphocyte

proliferation by phytohemagglutinin proliferation by phytohemagglutinin (Laudenslager et al 1983)(Laudenslager et al 1983)

–– Suppression of male reproductive Suppression of male reproductive behavior (Holmer et al 2003)behavior (Holmer et al 2003)

–– Social disruption accelerates diseases Social disruption accelerates diseases progression in SIV (Capitanio et al progression in SIV (Capitanio et al 1998)1998)



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What is environmental enrichment?What is environmental enrichment?

•• Enrichments are Enrichments are ‘‘biologically relevantbiologically relevant’’

•• Enrichments shield the animal from stressorsEnrichments shield the animal from stressors

•• Enrichments give the animal control Enrichments give the animal control –– Provide stimuli, or substrates for normal behaviorProvide stimuli, or substrates for normal behavior

–– Facilitate homeostatic goals of behavior Facilitate homeostatic goals of behavior

–– Increase the range of Increase the range of ‘‘normalnormal’’ behaviorbehavior

–– Decrease Decrease ‘‘abnormalabnormal’’ behaviorbehavior

•• They must be ratified by behavioral studiesThey must be ratified by behavioral studies

OutlineOutline

•• Theoretical conceptsTheoretical concepts

•• Sensory world, life history, and normal Sensory world, life history, and normal behaviorbehavior of miceof mice–– Natural historyNatural history

–– Sensory worldSensory world

–– Social Social behaviorsbehaviors•• Abnormal Abnormal behaviorbehavior

•• From a mouseFrom a mouse’’s point of views point of view



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The mouseness of mouseThe mouseness of mouse

•• House mice evolved in arid House mice evolved in arid grasslandsgrasslands

•• House mice are the only House mice are the only mice to live commensally mice to live commensally with humanswith humans

–– To follow us around the To follow us around the world they have had to be world they have had to be as adaptable to differing as adaptable to differing environments as humansenvironments as humans

Figure: Silver, 1995Figure: Silver, 1995

•• There are no There are no ‘‘wildwild’’ lab micelab mice–– Lab mice originate from hybridization of house mouse sub speciesLab mice originate from hybridization of house mouse sub species, and , and

related speciesrelated species–– ……specifically bred to look as unusual as possiblespecifically bred to look as unusual as possible

Mouse senses: vision Mouse senses: vision

•• Mouse vision is adapted to their niche as a Mouse vision is adapted to their niche as a nocturnal/crepuscular prey speciesnocturnal/crepuscular prey species–– Fixed focus, with very deep field of focusFixed focus, with very deep field of focus

–– Sensitive to movement, not formSensitive to movement, not form

•• Low spatial acuity: 0.6 cpd, (i.e. 1/50Low spatial acuity: 0.6 cpd, (i.e. 1/50thth human)human)

•• High ratio of rods to conesHigh ratio of rods to cones

–– Mice lack red cones, but have UV cones Mice lack red cones, but have UV cones

HUMAN

MOUSE UV



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What can mice see with an acuity of What can mice see with an acuity of 0.6 cpd (cycles per degree)?0.6 cpd (cycles per degree)?

1º

1.7º

≠

Mouse

Human

•• Acuity is measured as the angular Acuity is measured as the angular separation at which black and white separation at which black and white lines appear greylines appear grey

•• 1 1 ‘‘cyclecycle’’ ≈≈ 2 2 ‘‘pixelspixels’’

•• So a mouse can see with the same So a mouse can see with the same resolution at 1m, what we can see at resolution at 1m, what we can see at 50m50m

Mouse senses: hearingMouse senses: hearing

•• Mice hear well into the ultrasoundMice hear well into the ultrasound

•• Ultrasound Ultrasound maymay be used for echolocation (sonar)be used for echolocation (sonar)

•• Ultrasonic calls used in social interactions, pup Ultrasonic calls used in social interactions, pup distress calls, alarm calls, and male mating song!distress calls, alarm calls, and male mating song!

0 10 20 30 40 50 60 70 80 90 100kHz

Mice

Humans



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Mouse senses: hearingMouse senses: hearing

•• Mice hear well into the ultrasoundMice hear well into the ultrasound

•• Ultrasound Ultrasound maymay be used for echolocation (sonar)be used for echolocation (sonar)

•• Ultrasonic calls used in social interactions, pup Ultrasonic calls used in social interactions, pup distress calls, alarm calls, and male mating song!distress calls, alarm calls, and male mating song!

0 10 20 30 40 50 60 70 80 90 100kHz

Mice

Humans

(Audio: Holy 2005)

Mouse senses: touchMouse senses: touch

•• TouchTouch--sensitive body hairs detect the presence of sensitive body hairs detect the presence of surfaces against the body, including coversurfaces against the body, including cover

•• Mice find draughts, especially airMice find draughts, especially air--puffs aversivepuffs aversive

•• Whiskers are extremely sensitive and acute touchWhiskers are extremely sensitive and acute touch--sensors. Using active sensors. Using active ‘‘whiskingwhisking’’ movements, they can movements, they can detecting and discriminatedetecting and discriminate–– Textures (e.g. grades of sandpaper)Textures (e.g. grades of sandpaper)

–– Edges (e.g. sizes and shapes of openings)Edges (e.g. sizes and shapes of openings)

–– ObstaclesObstacles



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Sensory homunculi: Sensory homunculi: Mouse whiskers, human fingersMouse whiskers, human fingers

London Natural History Museum

Vanderhaeghen et al 2000 / Moskowitz, AMG

•• Sensory maps in the cortex Sensory maps in the cortex reflect neuronal number, reflect neuronal number, and hence the acuity and and hence the acuity and complexity of processingcomplexity of processing

Mouse senses: SmellMouse senses: Smell

•• Smell is the most important mouse senseSmell is the most important mouse sense

•• Smell is crucial to predatorSmell is crucial to predator--avoidance, feeding avoidance, feeding mating, parental, territorial, & social behaviorsmating, parental, territorial, & social behaviors

•• Urinary and plantar cues are also used in Urinary and plantar cues are also used in navigation, and edgenavigation, and edge--detectiondetection

•• Urinary, fecal, and plantar odors cue identity, Urinary, fecal, and plantar odors cue identity, age, sex, dominance, reproductive status, age, sex, dominance, reproductive status, relatedness, immunocompetence, health status, relatedness, immunocompetence, health status, and recent fright to other miceand recent fright to other mice



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Mouse senses: MagnetismMouse senses: Magnetism

•• Muheim et al (2006) Muheim et al (2006) trained mice to build trained mice to build nests in 1 of 4 nests in 1 of 4 orientationsorientations

•• The local magnetic field The local magnetic field was rotated by 90was rotated by 90ºº, 180, 180ººor 270or 270ºº

•• And mice built their And mice built their nests in the same nests in the same magnetic orientation, not magnetic orientation, not the physical locationthe physical location

Social structureSocial structure

•• Mice live in lose kin groups called Mice live in lose kin groups called ‘‘demesdemes’’

•• The degree of territoriality; homeThe degree of territoriality; home--range or range or territory size; and many other aspects of social territory size; and many other aspects of social behavior depend on the environmentbehavior depend on the environment–– Generally mice become more territorial, more Generally mice become more territorial, more

aggressive, and more infanticidal as population aggressive, and more infanticidal as population density increasesdensity increases

–– Territoriality may also vary with season, especially Territoriality may also vary with season, especially in colder environmentsin colder environments



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At the center of a homeAt the center of a home--range is a nest siterange is a nest site……

•• Mice build Mice build complex burrows complex burrows and nests, for and nests, for predator predator avoidance and avoidance and thermoregulationthermoregulation

•• Mice readily Mice readily burrow given the burrow given the chancechance

Photo: Chris SherwinPhoto: Chris Sherwin

Life historyLife history

•• Maternal experience affects offspring behavior Maternal experience affects offspring behavior from before birth to weaningfrom before birth to weaning

•• 1010--17 days: 17 days: First solid foodFirst solid food1414--15 days: 15 days: Eyes openEyes open2121--28 days: 28 days: First leave nest with parentFirst leave nest with parent2121--35 days: 35 days: Weaned to solid foodWeaned to solid food4545--84 days: 84 days: Sexual maturitySexual maturity45 days onwards: 45 days onwards: DispersalDispersal

•• Selecting dispersal strategy is essential to Selecting dispersal strategy is essential to reproductive successreproductive success



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The daily routine of a house mouseThe daily routine of a house mouse

•• Sleep during the day, and at nightSleep during the day, and at night……

•• Patrol home range (may involve hundreds of Patrol home range (may involve hundreds of meters of travel)meters of travel)–– Update urine marksUpdate urine marks

–– Assess neighborsAssess neighbors’’ urine marksurine marks

–– Detect and repel intrudersDetect and repel intruders

–– Detect and find potential mates Detect and find potential mates

–– Investigate novel objectsInvestigate novel objects

–– Find food (seeds, berries, insects, larvae, etc)Find food (seeds, berries, insects, larvae, etc)

•• Maintain nest, groom, tend to youngMaintain nest, groom, tend to young……

Social behaviorSocial behavior

•• Social behavior involves interactions between two or Social behavior involves interactions between two or more animals, from reproductive to territorial to more animals, from reproductive to territorial to altruistic behavioraltruistic behavior

•• Animals often come to Animals often come to ‘‘agreementsagreements’’ to avoid to avoid unnecessary conflictunnecessary conflict–– Territories Territories –– agreements in spaceagreements in space–– Dominance Dominance –– agreements in timeagreements in time

•• Mice show both kinds of behavior in their social Mice show both kinds of behavior in their social organizationorganization

•• Classifications of social behavior typically reflect the Classifications of social behavior typically reflect the question a researcher wants to ask... Letquestion a researcher wants to ask... Let’’s keep it simples keep it simple



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22½½ really important classesreally important classes

•• Affiliative Affiliative –– Reinforce social bonds Reinforce social bonds –– Mutual benefitMutual benefit–– Inherently enrichingInherently enriching

•• AggressiveAggressive–– Mediated Mediated –– one animal backs down by making a submissive one animal backs down by making a submissive

gesture, or fleeing before a fightgesture, or fleeing before a fight•• healthy and stable social hierarchyhealthy and stable social hierarchy

–– Escalated Escalated –– neither animal backs down, and the aggressive neither animal backs down, and the aggressive interaction escalates into a full fightinteraction escalates into a full fight

•• social unrest, potential for injury, and poor wellbeingsocial unrest, potential for injury, and poor wellbeing

•• The devil is in the detailsThe devil is in the details–– Escalated aggression is only a small percentage.Escalated aggression is only a small percentage.–– So if you donSo if you don’’t separate them, you are likely to lose information.t separate them, you are likely to lose information.

Affiliative: Attend, approach,Affiliative: Attend, approach,facial explorationfacial exploration



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Affiliative: Stretched Affiliative: Stretched attention postureattention posture

Affiliative: AllogroomingAffiliative: Allogrooming



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Aggression: Mediated aggressionAggression: Mediated aggression

Aggression: Mediated aggressionAggression: Mediated aggression



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Aggression: Escalated aggressionAggression: Escalated aggression

Importance and adaptability Importance and adaptability of social behaviorof social behavior

•• The social environment is a prominent and The social environment is a prominent and highly influential aspect of a mousehighly influential aspect of a mouse’’s worlds world

•• Mouse social behavior is highly adaptable: the Mouse social behavior is highly adaptable: the physical environment radically alters how physical environment radically alters how mice perceive and respond to social stimulimice perceive and respond to social stimuli–– Mice are more aggressive when interacting over a Mice are more aggressive when interacting over a

valued resourcevalued resource

–– Mice will suppress territorial aggression in cold Mice will suppress territorial aggression in cold weather and nest togetherweather and nest together

–– Maternal behavior and diet affect later tendencies Maternal behavior and diet affect later tendencies to aggressionto aggression



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Phenotypic Phenotypic plasticityplasticity

•• Mice are generalists: each generation may find itself Mice are generalists: each generation may find itself in a different environment, so their genome is a huge in a different environment, so their genome is a huge toolkit, but only a few tools are used in a lifetime.toolkit, but only a few tools are used in a lifetime.

•• In mice mothers can direct the development of stress In mice mothers can direct the development of stress physiology, and fearfulness. In rats this programming physiology, and fearfulness. In rats this programming continues across generations.continues across generations.

Francis et al. 1999; 2003

This plasticity involves changes in gene This plasticity involves changes in gene expression expression –– which can be inheritedwhich can be inherited

•• Different phenotypes of Different phenotypes of the Athe Avyvy allele, reflect allele, reflect different levels of different levels of epigenetic silencing epigenetic silencing (yellow = low silencing)(yellow = low silencing)

•• Offspring are more likely Offspring are more likely to resemble their mothersto resemble their mothers

•• Mothers or grandmothers Mothers or grandmothers fed methyl supplemented fed methyl supplemented diets produce more diets produce more pseudoagouti offspringpseudoagouti offspring

Morgan et al. 1999; Cropley et al. 2006



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OutlineOutline


•• Sensory world, life history, and normal Sensory world, life history, and normal behaviorbehavior of miceof mice

•• Abnormal Abnormal behaviorbehavior•• From a mouseFrom a mouse’’s point of views point of view

Standardized lab environments do Standardized lab environments do not allow this rich range of not allow this rich range of behaviorbehavior……



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…… and expose mice to important cues that and expose mice to important cues that they can do little or nothing about they can do little or nothing about ……

•• Cold and draughtsCold and draughts

•• No shelter or nest siteNo shelter or nest site–– high predation riskhigh predation risk

–– no ability to aid no ability to aid thermoregulationthermoregulation

–– no shelter from draughtsno shelter from draughts

•• Little opportunity for Little opportunity for locomotionlocomotion

•• Constant presence of Constant presence of human predatorshuman predators

…… of which most are social of which most are social ……

•• Unnatural early separation from motherUnnatural early separation from mother

•• No ability to control dispersalNo ability to control dispersal

•• Controlled sex ratios (and associated urinary effects)Controlled sex ratios (and associated urinary effects)

•• Unnaturally high stocking densityUnnaturally high stocking density–– small home rangesmall home range

•• Unnatural proximity of other breedersUnnatural proximity of other breeders

•• No ability to select matesNo ability to select mates–– Time to first litter, number of littersTime to first litter, number of litters

–– Pup number, viability, growth, weightPup number, viability, growth, weight

•• No shelter from aggressorsNo shelter from aggressors



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……and disrupt cues that are essential and disrupt cues that are essential to normal house mouse behaviorto normal house mouse behavior

•• PhysicalPhysical–– Background noise, especially ultrasoundBackground noise, especially ultrasound–– In nature, light levels at night are low, not zeroIn nature, light levels at night are low, not zero–– No UV lightNo UV light–– ?Magnetic fields??Magnetic fields?

•• SocialSocial–– Diffuse odor and auditory cues from nearby mice, Diffuse odor and auditory cues from nearby mice,

perhaps including motherperhaps including mother–– Urinary marks essential to social behavior are Urinary marks essential to social behavior are

disrupted every cage cleaningdisrupted every cage cleaning–– Inbred mice are nonInbred mice are non--distinguishable by odordistinguishable by odor

Abnormal behavior as a consequenceAbnormal behavior as a consequence

•• Standardized environments introduce stressors, or Standardized environments introduce stressors, or prevent or disrupt behaviors that would control themprevent or disrupt behaviors that would control them

•• Failure to control transforms stress into distressFailure to control transforms stress into distress

•• Abnormal behaviors are important indicatorsAbnormal behaviors are important indicators–– of persistent failed attempts to cope, and/orof persistent failed attempts to cope, and/or

–– of abnormal brain development or functionof abnormal brain development or function

–– And therefore of poor welfareAnd therefore of poor welfare

•• Enrichment should reduce abnormal behaviorEnrichment should reduce abnormal behavior

•• The two most common examples areThe two most common examples are–– Stereotypy Stereotypy

–– BarberingBarbering



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•• Stereotypies are Stereotypies are unvarying, unvarying, repetitive, repetitive, functionless functionless behaviorsbehaviors



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The causes of stereotypiesThe causes of stereotypies

•• Stereotypies are generally seen in barren Stereotypies are generally seen in barren environments in many speciesenvironments in many species

•• Stereotypies in mice are related toStereotypies in mice are related to–– Early weaning, lack of cover or nesting material, Early weaning, lack of cover or nesting material,

‘‘enrichmentsenrichments’’ that induce aggressionthat induce aggression

–– Motivation to explore or leave the cage?Motivation to explore or leave the cage?

•• Stereotypies in mice and other species may Stereotypies in mice and other species may involve the same abnormal brain function as involve the same abnormal brain function as stereotypies in human mental disorderstereotypies in human mental disorder–– Experimental impact?Experimental impact?

BarberingBarbering



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One mouse is the barber, plucking One mouse is the barber, plucking consistent patterns of hair lossconsistent patterns of hair loss

•• Patterns of hair loss are similarPatterns of hair loss are similar–– mean r = 0.87 for cagemates mean r = 0.87 for cagemates

mean r = 0.47 for nonmean r = 0.47 for non--cagemates cagemates (t=14.23; df=80; p <0.001)(t=14.23; df=80; p <0.001)

Dispelling some mythsDispelling some myths(Garner (Garner et alet al 2004)2004)

•• Barbering is not a dominance behaviorBarbering is not a dominance behavior–– Barbers are just as likely to be subordinate as Barbers are just as likely to be subordinate as

dominant to the animals they pluckdominant to the animals they pluck

•• Barbering involves group housed miceBarbering involves group housed mice–– Barbering is equally common in singly housed Barbering is equally common in singly housed

animalsanimals

•• Barbering always involves the whiskersBarbering always involves the whiskers–– 23% of barbers do not pluck whiskers23% of barbers do not pluck whiskers



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Impact of abnormal behaviorImpact of abnormal behavior

•• Psychological welfarePsychological welfare–– Stereotypy generally indicates welfare problemsStereotypy generally indicates welfare problems

–– Barbering is painful and involves sensory lossBarbering is painful and involves sensory loss

•• Medical welfareMedical welfare–– Barbering and stereotypy are associated with Barbering and stereotypy are associated with

differentdifferent measures of brain function that measures of brain function that correspond to these behaviors in human patientscorrespond to these behaviors in human patients

•• Therefore barbering and stereotypy may also Therefore barbering and stereotypy may also affect experimental outcomesaffect experimental outcomes

OutlineOutline




•• From a mouseFrom a mouse’’s point of views point of view–– Husbandry, Husbandry, behaviorbehavior and enrichmentand enrichment

–– behaviorbehavior and scienceand science



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Why do we house mice in plastic Why do we house mice in plastic shoebox cages?shoebox cages?

•• Mice find brightly lit, open, elevated spaces Mice find brightly lit, open, elevated spaces aversive aversive -- the basis of anxiety / fear teststhe basis of anxiety / fear tests

•• Light/dark box, open field, elevated plusLight/dark box, open field, elevated plus

•• Even in a safe environment they Even in a safe environment they ‘‘hug wallshug walls’’

Crowcroft, 1966

Why do we use cage ventilation?Why do we use cage ventilation?Why do we house mice at 20Why do we house mice at 20--2424ººC?C?

•• Mice find ventilation Mice find ventilation aversive (Baumans et al. aversive (Baumans et al. 2002)2002)

•• Mice in ventilated cages Mice in ventilated cages are more fearful are more fearful (Kallnick 2007)(Kallnick 2007)

•• Mice in ventilated cages Mice in ventilated cages show HPA sensitization, show HPA sensitization, and are immune and are immune suppressed (Neigh, suppressed (Neigh, 2005)2005)

•• Mice prefer warmer cages Mice prefer warmer cages (Gaskill et al., subm.)(Gaskill et al., subm.)

•• Mice are immune Mice are immune suppressed below 20suppressed below 20ººC C (Yamauchi 1983)(Yamauchi 1983)

Temperature20°C 25°C 30°C

Pop

ulat

ion

Tim

e B

udge

t(%

of t

ime)

0%

10%

20%

30%

40%

50%60%70%80%

*

* p-value< 0.05**p-value< 0.0001

**

**



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Why do we choose the enrichments Why do we choose the enrichments we do?we do?

•• For enrichment to be enriching, it must be For enrichment to be enriching, it must be ‘‘biologically relevantbiologically relevant’’

•• It must address a behavioral need, correct a It must address a behavioral need, correct a disruption of sensory cues, or allow mice to disruption of sensory cues, or allow mice to control their environmentcontrol their environment

•• Poker chips, marbles, leaving the radio on, etc. Poker chips, marbles, leaving the radio on, etc. are NOT enrichmentsare NOT enrichments

•• The enrichment best supported by good The enrichment best supported by good scientific data is nesting materialscientific data is nesting material

Biologically relevant enrichment Biologically relevant enrichment ––a case in pointa case in point

Deacon 2006

Nesting MaterialControl Nestlet Tissue Eco-bedding

Mea

n N

est S

core

0

1

2

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4

5

a

ab

a

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Hess et al, subm.



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Classifying enrichmentsClassifying enrichments(W(Wüürbel and Garner 2007)rbel and Garner 2007)

Pseudo-enrichments Conditionally beneficial enrichments

Beneficial enrichments

NoneNone NoneNoneNone to High: differs by None to High: differs by individual, sex, strain, or individual, sex, strain, or

managementmanagement

NoNo NoNo YesYes YesYes

HighHigh

Classification:

Welfare benefits:

Welfare detriments: High to LowHigh to Low Low to NoneLow to None High to none: as aboveHigh to none: as above

Mouse examples:MarblesMarbles11 ?? SheltersShelters22

Cage ventilationCage ventilation33Nesting Nesting materialmaterial44

Welfare consequences:

Impaired to Impaired to unaffectedunaffectedImpairedImpaired Impaired to benefitedImpaired to benefited BenefitedBenefited

Low to NoneLow to None

Biologically relevant?

Assessing enrichmentsAssessing enrichments

•• The first step in assessing enrichment is behavioralThe first step in assessing enrichment is behavioral–– Does the enrichment allow the desired control behaviors?Does the enrichment allow the desired control behaviors?

–– Does the enrichment reduce or prevent abnormal behavior?Does the enrichment reduce or prevent abnormal behavior?

–– Does the enrichment induce behavioral problems?Does the enrichment induce behavioral problems?

•• The second step is physiologicalThe second step is physiological–– Are stress measures reduced?Are stress measures reduced?

–– Is immune function and health improved?Is immune function and health improved?

•• If you skip to the first step, you run the risk of false If you skip to the first step, you run the risk of false negatives: the physiological data is almost impossible negatives: the physiological data is almost impossible to interpret without the context provided by behaviorto interpret without the context provided by behavior

•• If you skip the second step, you cannot assess the If you skip the second step, you cannot assess the broader impact of the enrichmentbroader impact of the enrichment



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Examples of behavioral assessmentExamples of behavioral assessment

•• Nest quality decreases with reduced cold stress Nest quality decreases with reduced cold stress

•• Shelters induce aggression Shelters induce aggression

Temperature (C)20 25 30

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0%

2%

4%

6%

8%

10%

Control Shelter + Fixedwheel

Shelter + Wheel

BeforeAfter

OutlineOutline




•• From a mouseFrom a mouse’’s point of views point of view–– Husbandry, Husbandry, behaviorbehavior and enrichmentand enrichment

–– behaviorbehavior and scienceand science



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Why do we use highWhy do we use high--throughput throughput phenotyping? phenotyping?

•• Many highMany high--throughput throughput measures are measures are notoriously difficult to notoriously difficult to replicate between labsreplicate between labs

•• Many highMany high--throughput throughput measures are measures are notoriously sensitive to notoriously sensitive to extraneous noiseextraneous noise

Many clearly do not measure what they Many clearly do not measure what they are supposed toare supposed to

•• The Morris water maze is The Morris water maze is one of the most widely used one of the most widely used –– and widely criticizedand widely criticized

•• It makes little sense for a It makes little sense for a desert speciesdesert species–– Marshland mice species Marshland mice species

generally perform bettergenerally perform better–– Gerlai & Clayton 1999Gerlai & Clayton 1999

•• Mice do not have the visual Mice do not have the visual acuity to use cues outside of acuity to use cues outside of the mazethe maze

•• Approximately 50% of the Approximately 50% of the variation between strains is variation between strains is due to visual abilitydue to visual ability

Brown & Wong, 2007



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Why do we use Why do we use ‘‘standardizedstandardized’’designs?designs?

•• Mice are phenotypically plastic Mice are phenotypically plastic –– the same genotype the same genotype produces different phenotypes in different produces different phenotypes in different environmentsenvironments

•• So when we So when we ‘‘standardizestandardize’’ the environment all we do is the environment all we do is make one particular GxE interaction that can never be make one particular GxE interaction that can never be replicated, and means nothing in terms of general replicated, and means nothing in terms of general validity.validity.

•• We certainly donWe certainly don’’t perform a human drug trial in only t perform a human drug trial in only 43 year old, vegetarian, middle class, white males, 43 year old, vegetarian, middle class, white males, from the same school and college, earning identical from the same school and college, earning identical incomes, living in identical houses in one small town incomes, living in identical houses in one small town in Wisconsin.in Wisconsin.

Standardization is the cause of poor Standardization is the cause of poor replicabilityreplicability

•• Human designs reduce sample size 5Human designs reduce sample size 5--10 fold, reduce false 10 fold, reduce false positives, and increase replicability (Garner et al 2006; Wpositives, and increase replicability (Garner et al 2006; Wüürbel rbel & Garner, 2007; Richter et al submitted)& Garner, 2007; Richter et al submitted)

Number of mice10 100 1000

Sim

ulat

ed P

- va

lue

of tr

eatm

ent e

ffect

0.0

0.2

0.4

0.6

0.8

1.0

C+ S+ I+ C+ S− I+ C+ S+ I− C+ S− I− C− S+ I+ C− S− I+ C− S+ I− C− S− I−



32

SummarySummary

•• Behavior is pivotal to good management, good Behavior is pivotal to good management, good science, and good welfarescience, and good welfare

•• Control, and the perception of control, is Control, and the perception of control, is pivotal in separating stress from distresspivotal in separating stress from distress

•• Enrichments must be biologically relevantEnrichments must be biologically relevant

•• Issues in housing, and experimentation, might Issues in housing, and experimentation, might be better resolved by taking the animalbe better resolved by taking the animal’’s point s point of view.of view.

Thanks to...Thanks to...

•• NIMHNIMH•• StudentsStudents

–– Brett Dufour, Brett Dufour, Brianna Gaskill, Brianna Gaskill, Sarah Hess, Sarah Hess, Chris Chris HowertonHowertonAria Prater, Aria Prater, Stephanie Rohr, Stephanie Rohr, Collette ThogersonCollette Thogerson

•• CollaboratorsCollaborators–– James Murray, James Murray,

Joy Mench, Joy Mench, Ed Pajor, Ed Pajor, Helene Richter,Helene Richter,Hanno Hanno WWüürbelrbel



33

Further readingFurther reading

1.1. P. P. CrowcroftCrowcroft, , Mice all overMice all over ((FoulisFoulis, London,, 1966)., London,, 1966).2.2. J. P. Garner, B. Dufour, L. E. Gregg, S. M. J. P. Garner, B. Dufour, L. E. Gregg, S. M. WeiskerWeisker, J. A. Mench, , J. A. Mench, Applied Applied

Animal behavior ScienceAnimal behavior Science 8989, 263, 263--282 (2004).282 (2004).3.3. J. P. Garner, in J. P. Garner, in Stereotypic Animal behavior: Fundamentals and Stereotypic Animal behavior: Fundamentals and

Applications to WelfareApplications to Welfare J. J. RushenRushen, G. Mason, Eds. (CABI, Wallingford, , G. Mason, Eds. (CABI, Wallingford, England, UK, 2006).England, UK, 2006).

4.4. N. Latham, G. Mason, N. Latham, G. Mason, Applied Animal behavior ScienceApplied Animal behavior Science 8686, 261, 261--289 289 (2004, 2004).(2004, 2004).

5.5. A. Olsson, K. A. Olsson, K. DahlbornDahlborn, , Laboratory AnimalsLaboratory Animals 3636, 243, 243--270 (Jul, 2002).270 (Jul, 2002).6.6. I. A. S. OlssonI. A. S. Olsson et al.et al., , Applied Animal behavior ScienceApplied Animal behavior Science 8181, 245, 245--264 264

(May 2, 2003).(May 2, 2003).7.7. C. Sherwin, in C. Sherwin, in Comfortable Quarters for Laboratory AnimalsComfortable Quarters for Laboratory Animals V. V.

Reinhardt, A. Reinhardt, Eds. (Animal Welfare Institute, WashingReinhardt, A. Reinhardt, Eds. (Animal Welfare Institute, Washington, ton, DC, 2002).DC, 2002).

8.8. L. M. Silver, L. M. Silver, Mouse genetics : concepts and applicationsMouse genetics : concepts and applications (Oxford (Oxford University Press, New York, 1995).University Press, New York, 1995).

9.9. H. H. WWüürbelrbel, J. P. Garner, , J. P. Garner, NC3RsNC3Rs 99, 1, 1--9 (2007).9 (2007).

dr. joseph garnerlibrary01.forbiddenmousecity.com/l007.pdf · mouse behavior charles river europe,...

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