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Age and Sex Influences on
  Crystallized, Fluid, and
General Intelligence in Mice
       Fred Gaudios, Henya Grossman
 Greg Hale, Stefan Kolata, Kenneth Light, Louis
       D. Matzel, and Melissa Zappulla

         David A. Townsend
       Department of Psychology
          Rutgers University
Crystallized Intelligence (Gc)

 In humans: Verbal IQ (Cattell 1971)
 WAIS: arithmetic, vocabulary, information,
  comprehension
 Differences in past learning

 Operationalize in mice?
  Beatty (1985) trained on RAM for entire life
  (3-26 months)
Age and Sex Influences on
  Crystallized, Fluid, and
General Intelligence in Mice


       David A Townsend
    Department of Psychology
       Rutgers University
Fluid Intelligence (Gf)

 The ability to form or construct
  representation of complex information
  (Lohman 1988)
 Representations must be accurate,
  detailed, and durable (Just 1986)
 Operations can be performed on the
  representations
   “ the ability to solve novel abstract
problems, to see relationships” ( Cattell)
“ the ability to solve novel abstract
problems, to see relationships” ( Cattell)
 Intelligence = reasoning ability
 Cattell’s Gf measures reasoning ability
 In Humans all performance on all IQ tests
  correlate (Spearman 1929, Jenson 1980) :
  revealing a general factor…….
“ the ability to solve novel abstract problems, to see relationships

          Gf is General Intelligence
   Binet and Simon (1905): the ability to judge well,
    to understand well, to reason well.
   Terman (1916): the capacity to form concepts and
    to grasp their significance.
   Wechsler (1939): the aggregate or global capacity
    of the individual to act purposefully, to think
    rationally, and to deal effectively with the
    environment.
   Gardner (1986): the ability or skill to solve
    problems or to fashion products which are valued
    within one or more cultural settings.
Age and Sex Influences on
   Fluid, and General
  Intelligence in Mice



        David A. Townsend
      Department of Psychology
         Rutgers University
General Intelligence
 To be intelligent is to
  understand, and to
  understand means to be
  aware of relationships
 ability to adapt
  effectively to the
  environment, either by
  making a change in
  oneself or by changing
  the environment or
  finding a new one
  (Encyclopedia
  Britannica)
General Intelligence

A general reasoning capacity
 useful in problem-solving tasks of
 all kinds       the aggregate or
                     (Kline 1991),


 global capacity of the individual to
 act purposefully and deal
 effectively with the environment
 ( Wechsler 1944)
General Intelligence

A. General Mental Ability (“g”)
  -   Spearman (1904,1920s)
  -   “g” = one core ability running through all
      cognitive abilities
  -   “g” = mental energy individuals bring to any
      intellectual task
  -   “g” = “mental engine”
  -   called “Two Factor Theory”

                  score = g + S (0r Gf + Gc)
A. General Learning Ability
    Examples of measures of “g”:
        Stanford-Binet Intelligence Scale
        Raven Progressive Matrices
        Cattell Culture Fair Intelligence Test

    Evidence for the existence of “g”:

    1.   many cognitive ability tests correlate with each other

    2.   even different types of tests correlate

    3.   measures of “g” correlate more highly with complex
         criteria
Group Differences
    in General
   Intelligence




                      Individual
                    Differences in
                       General
                     Intelligence
Group Differences in General
          Intelligence

Experimental Psychology
  Differences between
      group means


Normal vs. Disease state
Wildtype vs. Knockouts
Individual differences in General
              Intelligence

   Differential Psychology
Variation amongst individuals




     Nature vs. Nurture
 Molecular mechanisms of
       intelligence
Age and Sex Influences on
General Intelligence in Mice



         David A. Townsend
       Department of Psychology
          Rutgers University
Animal Models of Intelligence:
 Control of genotype
 Control of experience
 Control of environment
 Control of disease
 Control of diet

  Ability to explore neurobiological
                processes
The Efficacy of
      Synaptic
    Transmission
 Between Sensory
Receptors Predicts
  the Capacity for
     Behavioral
     Learning in
Individual Animals
A “general” influence on human
intelligence test performance is
the single most dominant
cognitive trait ever identified.

                   Robert Plomin,
                   Nature, 1999
CONSTRUCTION OF A TEST BATTERY
 Tasks should reflect a range of fundamental processes that
  all animals can master (i.e., Elemental Cognitive Tasks, or
  ECTs).

 Task Diversity: Tasks should impinge on distinct
  information processing strategies, sensory, motor,
  motivational, and brain systems.

 Transfer of Learning between tasks should be minimized.

 Time Constraints: Test battery must be sufficiently short so
  to negate the impact of differential effects of aging.

 Sensitivity to Variations in Learning: Animals are tested in
  acquisition, thus insuring sensitivity to real differences
  across animals and minimizing any impact of variations in
  long-term memory.
Test             Motor        Organic
                   Process                                                              Reinforcer
                                        Stimulus        Requirement    Deprivation

1. Lashley Maze    operant approach      egocentric/     ambulation      food        BioServ Pellet
                                           visual                                         (+)

  2. Passive      operant avoidance         place         passivity      none         noise/light
  Avoidance                                                                               (-)

  3. Spatial       operant escape        extramaze/       swimming       none           water
 Water Maze       spatial navigation       visual                                     immersion
                                                                                         (-)
 4. Odor          discrimination        olfactory        ambulation      food             rice
Discrimination                                                                            (+)

   5. Fear           association-       auditory         suppression     water        foot shock
 Conditioning         formation                                                           (-)

 6. Reinforced    pattern recognition      Prior         ambulation      water           cereal
  Alternation                             choice /                                        (+)
                                          memory
 7. Radial Arm    operant approach/     prior choice/    ambulation      food        Novas Pellet
     Maze         spatial navigation     WM/extra-                                      (+)
                                        maze/visual

  8. Spatial      operant approach/      extramaze/      ambulation      food          chocolate
  Plus Maze       spatial navigation       visual                                         (+)
Test             Motor        Organic
                  Process                                                              Reinforcer
                                       Stimulus        Requirement    Deprivation

 1. Lashley      operant approach egocentric/           ambulation      food         BioServ
    Maze                            visual                                            Pellet
                                                                                       (+)
  2. Passive     operant avoidance         place         passivity      none         noise/light
  Avoidance                                                                              (-)

  3. Spatial      operant escape        extramaze/       swimming       none           water
 Water Maze      spatial navigation       visual                                     immersion
                                                                                        (-)
 4. Odor         discrimination        olfactory        ambulation      food            rice
Discrimination                                                                          (+)

  5. Fear           association-       auditory         suppression     water        foot shock
Conditioning         formation                                                           (-)

6. Reinforced    pattern recognition      Prior         ambulation      water          cereal
 Alternation                             choice /                                       (+)
                                         memory
7. Radial Arm    operant approach/     prior choice/    ambulation      food        Novas Pellet
    Maze         spatial navigation     WM/extra-                                      (+)
                                       maze/visual

  8. Spatial     operant approach/      extramaze/      ambulation      food         chocolate
  Plus Maze      spatial navigation       visual                                        (+)
Lashley III Maze
Test             Motor        Organic
                   Process                                                              Reinforcer
                                        Stimulus        Requirement    Deprivation

1. Lashley Maze    operant approach      egocentric/     ambulation      food        BioServ Pellet
                                           visual                                         (+)

  2. Passive           operant             place          passivity      none         noise/light
  Avoidance           avoidance                                                           (-)
  3. Spatial       operant escape        extramaze/       swimming       none           water
 Water Maze       spatial navigation       visual                                     immersion
                                                                                         (-)
 4. Odor          discrimination        olfactory        ambulation      food             rice
Discrimination                                                                            (+)
   5. Fear           association-       auditory         suppression     water        foot shock
 Conditioning         formation                                                           (-)
 6. Reinforced    pattern recognition      Prior         ambulation      water           cereal
  Alternation                             choice /                                        (+)
                                          memory
 7. Radial Arm    operant approach/     prior choice/    ambulation      food        Novas Pellet
     Maze         spatial navigation     WM/extra-                                      (+)
                                        maze/visual
  8. Spatial      operant approach/      extramaze/      ambulation      food          chocolate
  Plus Maze       spatial navigation       visual                                         (+)
Passive Avoidance Step
        Down:




   Pre/Post
Test             Motor        Organic
                   Process                                                              Reinforcer
                                        Stimulus        Requirement    Deprivation

1. Lashley Maze    operant approach      egocentric/     ambulation      food        BioServ Pellet
                                           visual                                         (+)

  2. Passive      operant avoidance         place         passivity      none         noise/light
  Avoidance                                                                               (-)

  3. Spatial       operant escape        extramaze/      swimming        none           water
 Water Maze            spatial             visual                                     immersion
                     navigation                                                          (-)
 4. Odor          discrimination        olfactory        ambulation      food             rice
Discrimination                                                                            (+)

   5. Fear           association-       auditory         suppression     water        foot shock
 Conditioning         formation                                                           (-)

 6. Reinforced    pattern recognition      Prior         ambulation      water           cereal
  Alternation                             choice /                                        (+)
                                          memory
 7. Radial Arm    operant approach/     prior choice/    ambulation      food        Novas Pellet
     Maze         spatial navigation     WM/extra-                                      (+)
                                        maze/visual

  8. Spatial      operant approach/      extramaze/      ambulation      food          chocolate
  Plus Maze       spatial navigation       visual                                         (+)
Test             Motor        Organic
                   Process                                                              Reinforcer
                                        Stimulus        Requirement    Deprivation

1. Lashley Maze    operant approach      egocentric/     ambulation      food        BioServ Pellet
                                           visual                                         (+)
  2. Passive      operant avoidance        place          passivity      none         noise/light
  Avoidance                                                                               (-)
  3. Spatial       operant escape        extramaze/       swimming       none           water
 Water Maze       spatial navigation       visual                                     immersion
                                                                                         (-)
 4. Odor          discrimination        olfactory        ambulation      food            rice
Discrimination                                                                           (+)
   5. Fear           association-       auditory         suppression     water        foot shock
 Conditioning         formation                                                           (-)
 6. Reinforced    pattern recognition      Prior         ambulation      water           cereal
  Alternation                             choice /                                        (+)
                                          memory
 7. Radial Arm    operant approach/     prior choice/    ambulation      food        Novas Pellet
     Maze         spatial navigation     WM/extra-                                      (+)
                                        maze/visual
  8. Spatial      operant approach/      extramaze/      ambulation      food          chocolate
  Plus Maze       spatial navigation       visual                                         (+)
Odor Discrimination
target
                        Distracter




Distracter
Test             Motor        Organic
                   Process                                                              Reinforcer
                                        Stimulus        Requirement    Deprivation

1. Lashley Maze    operant approach      egocentric/     ambulation      food        BioServ Pellet
                                           visual                                         (+)
  2. Passive      operant avoidance         place         passivity      none         noise/light
  Avoidance                                                                               (-)
  3. Spatial       operant escape        extramaze/       swimming       none           water
 Water Maze       spatial navigation       visual                                     immersion
                                                                                         (-)
 4. Odor          discrimination        olfactory        ambulation      food             rice
Discrimination                                                                            (+)

  5. Fear            association-       auditory         suppression     water        foot shock
Conditioning          formation                                                           (-)
 6. Reinforced    pattern recognition      Prior         ambulation      water           cereal
  Alternation                             choice /                                        (+)
                                          memory
 7. Radial Arm    operant approach/     prior choice/    ambulation      food        Novas Pellet
     Maze         spatial navigation     WM/extra-                                      (+)
                                        maze/visual
  8. Spatial      operant approach/      extramaze/      ambulation      food          chocolate
  Plus Maze       spatial navigation       visual                                         (+)
LeDoux
Test             Motor        Organic
                  Process                                                              Reinforcer
                                       Stimulus        Requirement    Deprivation

1. Lashley Maze    operant approach     egocentric/     ambulation      food        BioServ Pellet
                                          visual                                         (+)

  2. Passive      operant avoidance        place         passivity      none         noise/light
  Avoidance                                                                              (-)

  3. Spatial       operant escape       extramaze/       swimming       none           water
 Water Maze       spatial navigation      visual                                     immersion
                                                                                        (-)
 4. Odor          discrimination       olfactory        ambulation      food             rice
Discrimination                                                                           (+)

   5. Fear           association-      auditory         suppression     water        foot shock
 Conditioning         formation                                                          (-)

6. Reinforced     pattern                 Prior         ambulation      water          cereal
 Alternation      recognition            choice /                                       (+)
                                         memory
 7. Radial Arm    operant approach/    prior choice/    ambulation      food        Novas Pellet
     Maze         spatial navigation    WM/extra-                                      (+)
                                       maze/visual

  8. Spatial      operant approach/     extramaze/      ambulation      food          chocolate
  Plus Maze       spatial navigation      visual                                         (+)
Trace Eyeblink Conditioning
                (Hippocampal-Dependent)

                                      500 ms

                             250 ms

         CS
   (83 db white noise)

                                               100 ms

          US
(0.7 mA periorbital shock)
Reinforced Alternation
Test            Motor        Organic
                   Process                                                             Reinforcer
                                        Stimulus       Requirement    Deprivation

1. Lashley Maze    operant approach      egocentric/    ambulation      food        BioServ Pellet
                                           visual                                        (+)
  2. Passive      operant avoidance         place        passivity      none         noise/light
  Avoidance                                                                              (-)
  3. Spatial       operant escape        extramaze/      swimming       none           water
 Water Maze       spatial navigation       visual                                    immersion
                                                                                        (-)
 4. Odor          discrimination        olfactory       ambulation      food             rice
Discrimination                                                                           (+)
   5. Fear           association-       auditory        suppression     water        foot shock
 Conditioning         formation                                                          (-)
 6. Reinforced    pattern recognition      Prior        ambulation      water           cereal
  Alternation                             choice /                                       (+)
                                          memory
7. Radial Arm         operant              prior        ambulation      food        Novas Pellet
    Maze          approach/ spatial       choice/                                      (+)
                     navigation
  8. Spatial      operant approach/      extramaze/     ambulation      food          chocolate
  Plus Maze       spatial navigation       visual                                        (+)
Radial Arm Maze
Test             Motor        Organic
                   Process                                                              Reinforcer
                                        Stimulus        Requirement    Deprivation

1. Lashley Maze    operant approach      egocentric/     ambulation      food        BioServ Pellet
                                           visual                                         (+)

  2. Passive      operant avoidance         place         passivity      none         noise/light
  Avoidance                                                                               (-)

  3. Spatial       operant escape        extramaze/       swimming       none           water
 Water Maze       spatial navigation       visual                                     immersion
                                                                                         (-)
 4. Odor          discrimination        olfactory        ambulation      food             rice
Discrimination                                                                            (+)

   5. Fear           association-       auditory         suppression     water        foot shock
 Conditioning         formation                                                           (-)

 6. Reinforced    pattern recognition      Prior         ambulation      water           cereal
  Alternation                             choice /                                        (+)
                                          memory
 7. Radial Arm    operant approach/     prior choice/    ambulation      food        Novas Pellet
     Maze         spatial navigation     WM/extra-                                      (+)
                                        maze/visual

  8. Spatial          operant            extramaze/      ambulation      food         chocolate
  Plus Maze       approach/ spatial        visual                                        (+)
                     navigation
Spatial Win/Stay in a Plus Maze
   START


           GOAL
Relative Performance
and Average Ranks (Ss
9-16)



      Exemplars:
      Ss13, Ss16
One-Trial Passive
  Avoidance
Spatial Water Maze
Associative Fear Conditioning
Good/Poor Learners
PRINCIPAL COMPONENT EXTRACTION

                                                               Loadings
    Large First Factor:               Lashley Maze               .50
                                      Passive Avoidance          .68
                                      Odor Discrimination        .32
                                      Fear Conditioning          .30
Evidence for the existence of “g”:
                                      Reinforced Alternation     .73
                                      Spatial Plus Maze          .74
     many cognitive ability tests     Water Maze                 .30
      correlate with each other
                                      Open Field % Open          .58
    even different types of tests
              correlate               Open Field Activity        -.19
                                      Running Speed               .17
                                      Defecation                  .10
   measures of “g” correlate more
                                      Body Weight                -.14
    highly with complex criteria

                                          Eigen Value           3.05
                                          % total variance       .29
Disassociations with General
              Intelligence
 Stress Reactivity
 Fear and Emotionality
 Experience and
  Novelty Seeking
 Working Memory
Variations in General Learning Abilities
                  vs.
   Variations in Response to Stress


 All tasks involve handling, and handling
  is stressful.

 Organic deprivation/aversive
  reinforcers are stressful.

 Individual animals vary in response to
  stress.
Stress Reactivity
 “the pattern of individual
  differences in learning                                       120                                            30       r = .14, ns                                                r = .71, p < .01
  performance attributed to                                     100
                                                                                                                        n = 10
                                                                                                                                                                              30
                                                                                                                                                                                   n = 11
  general learning ability is not                                                                              20
                                                                                                                                                                              20

  regulated by/ due to individual                                80




                                                                                         % Time in Open Arms




                                                                                                                                                        % Time in Open Arms
                                       Corticosterone (ng/ml)
                                                                                                               10
  differences in stress reactivity,                              60
                                                                                                                                                                              10


  and consequently, that stress                                  40                                             0                                                              0

  is not a determinant of general                                20
  learning abilities.“                                                                                                  20       40      60       80                                   50       100      150         200

                                                                      STRESS NO STRESS                              NO STRESS: Corticosterone (ng/ml)                               STRESS: Corticosterone (ng/ml)




 no consistent relationship was                                             The Role of Stress in
  found between basal or stressed                                              General Learning
  corticosterone levels and animals’
  tendency to enter the open                                                 Abilities (Grossman & Matzel)
  quadrants of an open field or the
  open arms of an elevated plus
  maze, measures of exploratory
  behavior
Disassociations with General
             Intelligence
 Stress Reactivity
 Fear and Emotionality
 Experience and Novelty Seeking
 Working Memory
Fear and Emotionality
                                                    PRINCIPAL COMPONENT EXTRACTION
 Common measures                                                                 Loadings
  used to quantify fear                                  Lashley Maze
                                                         Passive Avoidance
                                                                                     .50
                                                                                     .68

  or emotionality in                                     Odor Discrimination
                                                         Fear Conditioning
                                                                                     .32
                                                                                     .30
                                                         Reinforced Alternation     .73
  animals were                                           Spatial Plus Maze
                                                         Water Maze
                                                                                     .74
                                                                                     .30
  unrelated to individual                                Open Field % Open          .58

  animals’ general                                       Open Field Activity        -.19
                                                         Running Speed               .17
  learning abilities                                     Defecation
                                                         Body Weight
                                                                                     .10
                                                                                    -.14


              The Propensity for Exploration Covaries        Eigen Value           3.05
                   with General Learning Ability             % total variance       .29
              and is Independent of Stress Reactivity,
               Emotionality, and Behavioral Fitness

                Louis D. Matzel, David A. Townsend,
               Henya Grossman, Yu Ray Han, Gregory
                               Hale,
                 Kenneth Light, and Stefan Kolata
Disassociations of General
             Intelligence
 Stress Reactivity
 Fear and Emotionality
 Experience and Novelty Seeking
 Working Memory
Effects of Adaptation to Novelty on General
         Learning Abilities in Outbred Mice


 Light and Matzel


 Exploration does not drive learning abilities

 Possibility that exploration and learning co-
  vary
Is General Intelligence Dependent on
        the Efficacy of WM?
 Stress Reactivity
 Fear and Emotionality
 Experience and Novelty Seeking
 Working Memory
12/17/04
Group Differences in General
             Intelligence
 Knockout/Heterozygous/
       Wildtype
        PEA-15
        NrCam

Age and Sex
         ADHD
    Personality types
Age and Sex Influences on Learning
                Human
              Populations
      AGE:                  SEX:
Decline in Fluid   Do not differ in IQ
 intelligence       Spatial skills vs.
Impaired memory     Verbal skills
Slower NCV         Perceptual speed
Physiological      Associative
 decay               memory
Methods:

  SENSORY MOTOR / LEARNING TASKS:
 Male and Female BALBc mice
 Young (8 weeks) and Old (18+ months)
 16 animals/ group
( young females, young males, aged females,
   and aged males)
             MEMORY TASKS:
 8 animals per group
Methods:
 Sensory/Motor task:
11 measures of behavioral fitness
12 measures of activity
10+ measures of stress reactivity
6 motivational measures

 8 Learning Tasks:

 4 Memory Tasks:
   one STM, two LTM
Sensory motor tasks:
   Open field exploration
   Running wheel
   Balance beam
   Balance platform
   Roto-Rod Suspension
   Pain sensitivity
   Screen hanging
   Plus maze
   Escape response
   Light / dark preference
   Body weight
Methods:
 Sensory/Motor task:
11 measures of behavioral fitness
12 measures of activity
10+ measures of stress reactivity
6 motivational measures

 8 Learning Tasks:

 4 Memory Tasks:
   one STM, two LTM
Methods:
 Sensory/Motor task:
11 measures of behavioral fitness
12 measures of activity
10+ measures of stress reactivity
6 motivational measures

 8 Learning Tasks:

 4 Memory Tasks:
   one WM, two LTM
Learning tasks results:

                                                             Lashley 3 maze
                       Passive avoidance            25

                   4
                                                    20
                       Young Females
                       Young Males
                       Aged Females
                   3                                15
                       Aged Males




                                           Errors
Ratio (Post/Pre)




                                                    10
                   2


                                                     5

                   1

                                                     0
                                                         1    2    3      4   5

                   0                                              Trial
Learning tasks results:


                                Reinforced Alternation                       Odor Discrimination
                          1.0

                                                                   300

                          0.8
                                                                   250
% correct responses (x)




                                                                                                Females
                                                                   200
                          0.6                                                                   Males
                                                                                                OLD F
                                                                   150




                                                         Latency
                                                                                                OLD M

                          0.4
                                                                   100


                                                                   50
                          0.2

                                                                    0


                          0.0
                                                                         1      2           3             4

                                                                                    Trial
Learning task results:
                       Water Maze Acquisition                                                     Swim Speeds
                                                                                       10.0


              90                                 Females                                9.5

                                                                                        9.0
                                                 Males
                                                                                        8.5
                                                 OLD Females
              80




                                                               cm/s
                                                                                        8.0
                                                 OLD Males
                                                                                        7.5

              70                                                                        7.0

                                                                                        6.5
Latency (s)




                                                                                        6.0
              60                                                                              1     2            10

                                                                                                         trial


              50                                                                                  Path lenghts
                                                                                       22

                                                                                       20
              40                                                                       18




                                                               Ratio ( Path/Optimal)
                                                                                       16

              30                                                                       14

                                                                                       12

                                                                                       10
              20                                                                        8

                   1   2   3   4   5 24h 6   7   8   9   10                             6

                                                                                        4

                                    Trial                                                     1     2            10

                                                                                                        Trial
Learning tasks results, Spatial:

                                 Errors
                                                                                                          Ram Aquisition

         5
                                                                                             25
                                          Trial vs Females
         4
                                          Trial vs Males
                                          Trial vs OLD F                                     20




                                                               Errors to 7 correct choices
                                          Trial vs OLD M
         3
Errors




                                                                                             15


         2
                                                                                             10


         1
                                                                                              5


         0
             1   2   3   4   5    24h     6   7   8   9   10                                  0
                                                                                                  1   2         3          4   5
                                 Trials
Norman M. White
 Multiple Parallel Memory Systems in the
  Brain of the Rat

 Different subtypes and systems of spatial
  skills

               Hippocampus                              Amygdala
      Learned relationships about cues   Acquisition of reward based responses


                Water maze                        RAM, Win/Stay
Learning tasks results:
                         Fear conditioning
                   4

                                        Young Females
                                        Young Males
                                        Aged Females
                   3                    Aged Males
Ratio( Post/Pre)




                   2




                   1




                   0
Learning tasks results:
                       Fear conditioning
                   4
                                                                        12

                   3                                                          Fear asymptotic training
                                                                              Licks8during fear training
                                                                                     training trials
Ratio( Post/Pre)




                                                                        10
                   2                                                    500



                   1
                                                                        400
                                                                          8
                   0




                                                      Mean # of licks
                                                         Post/pre
                                                                        300
                                                                          6
                         Young Females
                                                                        200
                         Young Males
                         Aged Females                                     4
                         Aged Males                                     100



                                                                          2
                                                                          0




                                                                          0
Conclusions:
 Behavioral Fitness, Stress reactivity:
        few differences, (weight related)
                   Learning:
Few Differences between groups
  Age impairs H20 performance
   Other Spatial tasks spared

                             Memory:
   LTM: Few differences (age tends to impair odor discrimination)
WM: Males less impaired than females by working memory manipulation
Conclusions:                        General Learning Abilities:

                                      Factor Scores
                                             Variable
                                              LASHLEY
                                                               Factor 1
                                                              .783981
                                                                           Factor 2
                                                                          .013342
                        Rankings

                                                    AVOID     505789      -.156728
               50
                                   Correlation Matrices
                                               FEAR  .787095              .162388
               40

                                                     H2O     -.284625     .208772
                                     Factor Structure .061637
Average rank




               30
                                              WINSTAY                     .880633
                                        Females
               20
                                        Males        RAM     -.104380     .729405
                      suggest no difference in1.585674 1.402243
                                                     overall
                                        OLD F
                                        OLD M
               10                       Explained
                                        var.
                0
                       differences in learning abilities .233707
                                        Prop. total .264279
                     based on age/sex: but variability
                    differences in components used to
                           assess learning abilities
Why were the expected groups
      differences not observed?
 Inbred Mice (clones)

 Mortality selection of aged mice (NIA mice)

 Balb/c          (blood work)
Matzel Lab:
 Our Knowledge and expertise may be
  domain-specific, but the means by which
  we become knowledgeable and expert may
  be entirely general (Mackintosh 1998)
Memory tasks:

            Long Term Memory:
 Odor discrimination (30 days)
 Lashley 3 maze (30 days)
 Fear c


           Working Memory:
 RAM delay (120s)
Long Term Memory tasks results:
                                           Lashley Maze
         16


         14
                                                Females
                                               Fear Conditioning:
                                                Males
         12
                                                   OLD Females
         10                                        OLD decay
                                                   No Males             (30d)
          8                               No age of sex differences
Errors




          6


          4


          2


          0



              1   2   3   4   5   6   7    8   9    10   11   12   13   14   15   30d   A   B   C
                                               Trial
Long Term Memory tasks results:

                      Odor Discrimnation                                                                Long Term Memory
                                                                                                        Odor retention test
                                                                                                       1 month post training
         8
                                                                                                 600




                                                        % increase in errors from Training(T4)
         6                                                                                       500


                                                                                                 400
         4
errors




                                                                                                 300


         2
                                                                                                 200


                                                                                                 100
         0

                                                                                                   0


              1   2       3           4   30 Days   5

                              trial
                                                                                                            Females
                                                                                                            Males
                                                                                                            OLD F
                                                                                                            OLD M
Working Memory:
                                                           Working memory test in RAM
                                                                         DELAY
 Mice trained to criteria
 Allowed to make 4                                   20

                                                      18
  choices                                             16
                                                               Females
                                                               Males




                             Errors after 120s hold
 Held 120s                                           14
                                                               OLD F
                                                               OLD M

                                                      12
 Errors until 3
                                                      10
  additional correct                                   8
  choices                                              6

 Further testing                                      4

                                                       2

                                                       0
Age and Sex Influences on Learning
         Abilities in Mice




   David A. Townsend, Greg Hale, Stefan Kolata, Ken Light, and Louis D. Matzel
                                  Department of Psychology
                     Program in Biopsychology & Behavioral Neuroscience
                              Rutgers University, Piscataway NJ
Hormonal and Sex Differences
                             Have No Effect on Water Maze
                                     Preformance
                                    Performance

                                                 OVX
Mean+ SE Latency

                   100
                                                 FEMALE
                                                 MALE
     (sec)




                    50                       +
                                                       +
                                   *                       +


                     0
                         0         1        2          3   4
                                            DAY

                                 + p < .05 vs. Day 1
                                 * p < .05 vs Male/OVX

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Dec3 a

  • 1. Age and Sex Influences on Crystallized, Fluid, and General Intelligence in Mice Fred Gaudios, Henya Grossman Greg Hale, Stefan Kolata, Kenneth Light, Louis D. Matzel, and Melissa Zappulla David A. Townsend Department of Psychology Rutgers University
  • 2. Crystallized Intelligence (Gc)  In humans: Verbal IQ (Cattell 1971)  WAIS: arithmetic, vocabulary, information, comprehension  Differences in past learning  Operationalize in mice? Beatty (1985) trained on RAM for entire life (3-26 months)
  • 3. Age and Sex Influences on Crystallized, Fluid, and General Intelligence in Mice David A Townsend Department of Psychology Rutgers University
  • 4. Fluid Intelligence (Gf)  The ability to form or construct representation of complex information (Lohman 1988)  Representations must be accurate, detailed, and durable (Just 1986)  Operations can be performed on the representations “ the ability to solve novel abstract problems, to see relationships” ( Cattell)
  • 5. “ the ability to solve novel abstract problems, to see relationships” ( Cattell)  Intelligence = reasoning ability  Cattell’s Gf measures reasoning ability  In Humans all performance on all IQ tests correlate (Spearman 1929, Jenson 1980) : revealing a general factor…….
  • 6. “ the ability to solve novel abstract problems, to see relationships Gf is General Intelligence  Binet and Simon (1905): the ability to judge well, to understand well, to reason well.  Terman (1916): the capacity to form concepts and to grasp their significance.  Wechsler (1939): the aggregate or global capacity of the individual to act purposefully, to think rationally, and to deal effectively with the environment.  Gardner (1986): the ability or skill to solve problems or to fashion products which are valued within one or more cultural settings.
  • 7. Age and Sex Influences on Fluid, and General Intelligence in Mice David A. Townsend Department of Psychology Rutgers University
  • 8. General Intelligence  To be intelligent is to understand, and to understand means to be aware of relationships  ability to adapt effectively to the environment, either by making a change in oneself or by changing the environment or finding a new one (Encyclopedia Britannica)
  • 9. General Intelligence A general reasoning capacity useful in problem-solving tasks of all kinds the aggregate or (Kline 1991), global capacity of the individual to act purposefully and deal effectively with the environment ( Wechsler 1944)
  • 10. General Intelligence A. General Mental Ability (“g”) - Spearman (1904,1920s) - “g” = one core ability running through all cognitive abilities - “g” = mental energy individuals bring to any intellectual task - “g” = “mental engine” - called “Two Factor Theory” score = g + S (0r Gf + Gc)
  • 11. A. General Learning Ability  Examples of measures of “g”:  Stanford-Binet Intelligence Scale  Raven Progressive Matrices  Cattell Culture Fair Intelligence Test  Evidence for the existence of “g”: 1. many cognitive ability tests correlate with each other 2. even different types of tests correlate 3. measures of “g” correlate more highly with complex criteria
  • 12. Group Differences in General Intelligence Individual Differences in General Intelligence
  • 13. Group Differences in General Intelligence Experimental Psychology Differences between group means Normal vs. Disease state Wildtype vs. Knockouts
  • 14. Individual differences in General Intelligence Differential Psychology Variation amongst individuals Nature vs. Nurture Molecular mechanisms of intelligence
  • 15. Age and Sex Influences on General Intelligence in Mice David A. Townsend Department of Psychology Rutgers University
  • 16. Animal Models of Intelligence:  Control of genotype  Control of experience  Control of environment  Control of disease  Control of diet Ability to explore neurobiological processes
  • 17. The Efficacy of Synaptic Transmission Between Sensory Receptors Predicts the Capacity for Behavioral Learning in Individual Animals
  • 18. A “general” influence on human intelligence test performance is the single most dominant cognitive trait ever identified. Robert Plomin, Nature, 1999
  • 19. CONSTRUCTION OF A TEST BATTERY  Tasks should reflect a range of fundamental processes that all animals can master (i.e., Elemental Cognitive Tasks, or ECTs).  Task Diversity: Tasks should impinge on distinct information processing strategies, sensory, motor, motivational, and brain systems.  Transfer of Learning between tasks should be minimized.  Time Constraints: Test battery must be sufficiently short so to negate the impact of differential effects of aging.  Sensitivity to Variations in Learning: Animals are tested in acquisition, thus insuring sensitivity to real differences across animals and minimizing any impact of variations in long-term memory.
  • 20. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 21. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley operant approach egocentric/ ambulation food BioServ Maze visual Pellet (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 23. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant place passivity none noise/light Avoidance avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 24. Passive Avoidance Step Down: Pre/Post
  • 25. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial visual immersion navigation (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 26.
  • 27. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 28. Odor Discrimination target Distracter Distracter
  • 29. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 31. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern Prior ambulation water cereal Alternation recognition choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 32. Trace Eyeblink Conditioning (Hippocampal-Dependent) 500 ms 250 ms CS (83 db white noise) 100 ms US (0.7 mA periorbital shock)
  • 34. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant prior ambulation food Novas Pellet Maze approach/ spatial choice/ (+) navigation 8. Spatial operant approach/ extramaze/ ambulation food chocolate Plus Maze spatial navigation visual (+)
  • 36. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation 1. Lashley Maze operant approach egocentric/ ambulation food BioServ Pellet visual (+) 2. Passive operant avoidance place passivity none noise/light Avoidance (-) 3. Spatial operant escape extramaze/ swimming none water Water Maze spatial navigation visual immersion (-) 4. Odor discrimination olfactory ambulation food rice Discrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory 7. Radial Arm operant approach/ prior choice/ ambulation food Novas Pellet Maze spatial navigation WM/extra- (+) maze/visual 8. Spatial operant extramaze/ ambulation food chocolate Plus Maze approach/ spatial visual (+) navigation
  • 37. Spatial Win/Stay in a Plus Maze START GOAL
  • 38. Relative Performance and Average Ranks (Ss 9-16) Exemplars: Ss13, Ss16
  • 39. One-Trial Passive Avoidance
  • 43. PRINCIPAL COMPONENT EXTRACTION Loadings Large First Factor: Lashley Maze .50 Passive Avoidance .68 Odor Discrimination .32 Fear Conditioning .30 Evidence for the existence of “g”: Reinforced Alternation .73 Spatial Plus Maze .74 many cognitive ability tests Water Maze .30 correlate with each other Open Field % Open .58 even different types of tests correlate Open Field Activity -.19 Running Speed .17 Defecation .10 measures of “g” correlate more Body Weight -.14 highly with complex criteria Eigen Value 3.05 % total variance .29
  • 44. Disassociations with General Intelligence  Stress Reactivity  Fear and Emotionality  Experience and Novelty Seeking  Working Memory
  • 45. Variations in General Learning Abilities vs. Variations in Response to Stress  All tasks involve handling, and handling is stressful.  Organic deprivation/aversive reinforcers are stressful.  Individual animals vary in response to stress.
  • 46. Stress Reactivity  “the pattern of individual differences in learning 120 30 r = .14, ns r = .71, p < .01 performance attributed to 100 n = 10 30 n = 11 general learning ability is not 20 20 regulated by/ due to individual 80 % Time in Open Arms % Time in Open Arms Corticosterone (ng/ml) 10 differences in stress reactivity, 60 10 and consequently, that stress 40 0 0 is not a determinant of general 20 learning abilities.“ 20 40 60 80 50 100 150 200 STRESS NO STRESS NO STRESS: Corticosterone (ng/ml) STRESS: Corticosterone (ng/ml)  no consistent relationship was The Role of Stress in found between basal or stressed General Learning corticosterone levels and animals’ tendency to enter the open Abilities (Grossman & Matzel) quadrants of an open field or the open arms of an elevated plus maze, measures of exploratory behavior
  • 47. Disassociations with General Intelligence  Stress Reactivity  Fear and Emotionality  Experience and Novelty Seeking  Working Memory
  • 48. Fear and Emotionality PRINCIPAL COMPONENT EXTRACTION  Common measures Loadings used to quantify fear Lashley Maze Passive Avoidance .50 .68 or emotionality in Odor Discrimination Fear Conditioning .32 .30 Reinforced Alternation .73 animals were Spatial Plus Maze Water Maze .74 .30 unrelated to individual Open Field % Open .58 animals’ general Open Field Activity -.19 Running Speed .17 learning abilities Defecation Body Weight .10 -.14 The Propensity for Exploration Covaries Eigen Value 3.05 with General Learning Ability % total variance .29 and is Independent of Stress Reactivity, Emotionality, and Behavioral Fitness Louis D. Matzel, David A. Townsend, Henya Grossman, Yu Ray Han, Gregory Hale, Kenneth Light, and Stefan Kolata
  • 49. Disassociations of General Intelligence  Stress Reactivity  Fear and Emotionality  Experience and Novelty Seeking  Working Memory
  • 50. Effects of Adaptation to Novelty on General Learning Abilities in Outbred Mice  Light and Matzel  Exploration does not drive learning abilities  Possibility that exploration and learning co- vary
  • 51. Is General Intelligence Dependent on the Efficacy of WM?  Stress Reactivity  Fear and Emotionality  Experience and Novelty Seeking  Working Memory
  • 53. Group Differences in General Intelligence  Knockout/Heterozygous/ Wildtype  PEA-15  NrCam Age and Sex  ADHD  Personality types
  • 54. Age and Sex Influences on Learning Human Populations AGE: SEX: Decline in Fluid Do not differ in IQ intelligence Spatial skills vs. Impaired memory Verbal skills Slower NCV Perceptual speed Physiological Associative decay memory
  • 55. Methods: SENSORY MOTOR / LEARNING TASKS:  Male and Female BALBc mice  Young (8 weeks) and Old (18+ months)  16 animals/ group ( young females, young males, aged females, and aged males) MEMORY TASKS:  8 animals per group
  • 56. Methods:  Sensory/Motor task: 11 measures of behavioral fitness 12 measures of activity 10+ measures of stress reactivity 6 motivational measures  8 Learning Tasks:  4 Memory Tasks: one STM, two LTM
  • 57. Sensory motor tasks:  Open field exploration  Running wheel  Balance beam  Balance platform  Roto-Rod Suspension  Pain sensitivity  Screen hanging  Plus maze  Escape response  Light / dark preference  Body weight
  • 58. Methods:  Sensory/Motor task: 11 measures of behavioral fitness 12 measures of activity 10+ measures of stress reactivity 6 motivational measures  8 Learning Tasks:  4 Memory Tasks: one STM, two LTM
  • 59. Methods:  Sensory/Motor task: 11 measures of behavioral fitness 12 measures of activity 10+ measures of stress reactivity 6 motivational measures  8 Learning Tasks:  4 Memory Tasks: one WM, two LTM
  • 60. Learning tasks results: Lashley 3 maze Passive avoidance 25 4 20 Young Females Young Males Aged Females 3 15 Aged Males Errors Ratio (Post/Pre) 10 2 5 1 0 1 2 3 4 5 0 Trial
  • 61. Learning tasks results: Reinforced Alternation Odor Discrimination 1.0 300 0.8 250 % correct responses (x) Females 200 0.6 Males OLD F 150 Latency OLD M 0.4 100 50 0.2 0 0.0 1 2 3 4 Trial
  • 62. Learning task results: Water Maze Acquisition Swim Speeds 10.0 90 Females 9.5 9.0 Males 8.5 OLD Females 80 cm/s 8.0 OLD Males 7.5 70 7.0 6.5 Latency (s) 6.0 60 1 2 10 trial 50 Path lenghts 22 20 40 18 Ratio ( Path/Optimal) 16 30 14 12 10 20 8 1 2 3 4 5 24h 6 7 8 9 10 6 4 Trial 1 2 10 Trial
  • 63. Learning tasks results, Spatial: Errors Ram Aquisition 5 25 Trial vs Females 4 Trial vs Males Trial vs OLD F 20 Errors to 7 correct choices Trial vs OLD M 3 Errors 15 2 10 1 5 0 1 2 3 4 5 24h 6 7 8 9 10 0 1 2 3 4 5 Trials
  • 64. Norman M. White  Multiple Parallel Memory Systems in the Brain of the Rat  Different subtypes and systems of spatial skills Hippocampus Amygdala Learned relationships about cues Acquisition of reward based responses Water maze RAM, Win/Stay
  • 65. Learning tasks results: Fear conditioning 4 Young Females Young Males Aged Females 3 Aged Males Ratio( Post/Pre) 2 1 0
  • 66. Learning tasks results: Fear conditioning 4 12 3 Fear asymptotic training Licks8during fear training training trials Ratio( Post/Pre) 10 2 500 1 400 8 0 Mean # of licks Post/pre 300 6 Young Females 200 Young Males Aged Females 4 Aged Males 100 2 0 0
  • 67. Conclusions:  Behavioral Fitness, Stress reactivity: few differences, (weight related)  Learning: Few Differences between groups Age impairs H20 performance Other Spatial tasks spared  Memory: LTM: Few differences (age tends to impair odor discrimination) WM: Males less impaired than females by working memory manipulation
  • 68. Conclusions:  General Learning Abilities: Factor Scores Variable LASHLEY Factor 1 .783981 Factor 2 .013342 Rankings AVOID 505789 -.156728 50 Correlation Matrices FEAR .787095 .162388 40 H2O -.284625 .208772 Factor Structure .061637 Average rank 30 WINSTAY .880633 Females 20 Males RAM -.104380 .729405 suggest no difference in1.585674 1.402243 overall OLD F OLD M 10 Explained var. 0 differences in learning abilities .233707 Prop. total .264279 based on age/sex: but variability differences in components used to assess learning abilities
  • 69. Why were the expected groups differences not observed?  Inbred Mice (clones)  Mortality selection of aged mice (NIA mice)  Balb/c (blood work)
  • 71.  Our Knowledge and expertise may be domain-specific, but the means by which we become knowledgeable and expert may be entirely general (Mackintosh 1998)
  • 72. Memory tasks: Long Term Memory:  Odor discrimination (30 days)  Lashley 3 maze (30 days)  Fear c Working Memory:  RAM delay (120s)
  • 73. Long Term Memory tasks results: Lashley Maze 16 14 Females Fear Conditioning: Males 12 OLD Females 10 OLD decay No Males (30d) 8 No age of sex differences Errors 6 4 2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 30d A B C Trial
  • 74. Long Term Memory tasks results: Odor Discrimnation Long Term Memory Odor retention test 1 month post training 8 600 % increase in errors from Training(T4) 6 500 400 4 errors 300 2 200 100 0 0 1 2 3 4 30 Days 5 trial Females Males OLD F OLD M
  • 75. Working Memory: Working memory test in RAM DELAY  Mice trained to criteria  Allowed to make 4 20 18 choices 16 Females Males Errors after 120s hold  Held 120s 14 OLD F OLD M 12  Errors until 3 10 additional correct 8 choices 6  Further testing 4 2 0
  • 76. Age and Sex Influences on Learning Abilities in Mice David A. Townsend, Greg Hale, Stefan Kolata, Ken Light, and Louis D. Matzel Department of Psychology Program in Biopsychology & Behavioral Neuroscience Rutgers University, Piscataway NJ
  • 77.
  • 78. Hormonal and Sex Differences Have No Effect on Water Maze Preformance Performance OVX Mean+ SE Latency 100 FEMALE MALE (sec) 50 + + * + 0 0 1 2 3 4 DAY + p < .05 vs. Day 1 * p < .05 vs Male/OVX

Editor's Notes

  1. Well, When David 1 st asked me to speak today, my emotions ran the gamet from fear and trepidation to terror. However, I thought I had a really cool title. Unfortunately, the title and this slide is very misleading. First of all, since you all know me, and I’m going to be talking for more than 5 m, its obvious that I couldn’t have done ALL this work, So I would like to acknowledge the members of my lab who do more than scower the hall for cookies
  2. Crystallized Intelligence is difficult to study in animals Crystallized Intelligence is: Now, in 1989 studied crystallized intelligence in mice by training mice for 4 months in a RAM. Since this is longer than my marriages, I was unwilling to do this
  3. So lets get rid of that And move on to Fluid intelligence
  4. Fluid intelligence is the ability to deal with novel problems and successfully solve them. I’d like to focus on this definition of Fluid intelligence from Cattell’s early work. Read….
  5. Fluid intelligence is very closely related to the notion we all have of what intelligence is, reasoning ability and dealing with novel problems. In humans, especially in IQ tests, if an individual does well on one intelligence measure or test, there is a good change they perform well most others. This correlation, which is hierarchal in nature produces a large general factor in factor analytical measuments. This general factor represents the idea of a underlying mechanism that drives and affects measurements of intelligence. In Cattell’s theories this underlying ability is Gf. But Gf can also be interpreted as what we imply when we discuss general intelligence.
  6. So especially in animal models of intelligence, where, like we do, animals intelligence is measures during acquisition, Gf, solving novel problems, is how we measure General intelligence or learning abilities.
  7. So, out with fluid intelligence and onto general intelligence.
  8. As you all know, Human intelligence is one of the most therouly studied branchs of psychology, So one would think that we had an agreed upon paradigm and definition of what general intelligence is. Well we don’t. These are two definitions of general intelligence, out of .thousands. Intelligence is sort of pornography, its hard to define, but we know it when we see it.
  9. Though intelligence can be a generic term for stimulus apprehension, attention,perception,discrimination, generalization, conditioning, learning, STM, LTM, thinking, reasoning, inference and problem solving
  10. The idea that there is an underlying process, general intelligence or G, that underlies performance on all measures of cognitive abilities is not new, dates back to Darwin and Galton. Spearman formalized the concept theoretically and mathematically using factor analyze over 80 years ago. The idea is that in any novel problem solving there are factors that influence solving a task that are specific to that task, BUT, that there is an underlying mechanism, brain based, that influences performance on all cognitive tasks and abilities. Spearman identifies this as the mental engine or the available mental energy to solve problems
  11. Now, there is overwhelming evidence that a General learning ability exists and that indiduals differ, there is natural variation in a population, in learning abilities. Again, we recognize different levels of intelligence when we see them, and if and individual performs well on one test of learning abilities they almost universally perform well on other measurements.
  12. There are two ways to explore general intelligence, both of which we pursue in our lab. You can look and group differences in intelligence, and difference in general intelligence, learning abliltes btw. Indiduals.
  13. Group difference is the usually method, as neuroscientists, we use to explore psychology processes, including learning abilities. The scant data I will be presented today is from a study looking at difference in learning abilities btw. Different populations.
  14. Individual differences explore the natural variation within a population in in intelligence. This perspective has been very useful for us in trying to operationalize and define what is general intelligence and what the possible neural substrates of it are. I’m going to spend some time discussing how we explore individual differences in intelligence
  15. Well, Back to my title slide here. I am going to talk about mice. But why, there is some much research and debate of general intelligence in humans, but there is a pacidity of research using animal models. Well animal model present some unique advantages.
  16. Control of external factor is one of the most important. But the greatest benefit of using mice is the ability to explore the neural mechanisms that drive and create general intelligence
  17. We began interesting in this when Lou and Chet reported that, in hermisdial, which are little sea snails, greater synatitic efficacy resulted in enhanced learning abilities.
  18. A &quot;general&quot; influence on humans&apos; performance across diverse tests of cognitive abilities has been described as the most dominant and one of the most heritable cognitive traits ever identified (Plomin, 1999; Plomin and Spinath, 2002). The reason I’ve placed this slide here, is to emphasize, that though we are using a mice model of general intelligence, we are interested in defining learning abilities in Humans, and what drives variations in human general intelligence.
  19. What we have done is create a sort of intelligence test for mice. A battery of diverse tests, akin to human IQ tests, to identifiy and explore general intelligence. The tasks are simple and diverse so that individual differences in learning abilities are easy to identify. We test our mice during acquisition, during the novel problem solving, In humans, task acquisition in highly correlated with all measures of general intelligence.
  20. Here are the 8 learning tasks we use Lashley Maze, Odor Discrimination, Passive Avoidance, Spatial Plus Maze, Spatial Water Maze, Fear Conditioning, and Reinforced Alternation). Each task makes different demand on animals cognitive abilities. I’m going to briefly run through these tasks the Tasks reflect a range of fundamental processes that all animals can master (i.e., Elemental Cognitive Tasks, or ECTs). We also consider Task Diversity : Tasks should impinge on distinct information processing strategies, sensory, motor, motivational, and brain systems. Transfer of Learning between tasks was minimized. of course we consider Time Constraints : the Test battery must be sufficiently short so to negate the impact of differential effects of aging. We test Animals in a cquisition , thus insuring sensitivity to real differences across animals and minimizing any impact of variations in long-term memory. We feel this strategy insures Sensitivity to Variations in Learning : Since Age/sex have shown sexual dimorphism is Spatial skill, 3 tests of spatial skills, H20 maze, RAM, and spatial Win stay.
  21. First the Lashley 3 Maze.
  22. Here a mouse learns to travel through a maze For a reward. Over trials, the latency of rats to locate the goal box decreases, as do their errors (i.e., wrong turns or retracing). Animals relay on allocentic, or fixed motor patterns to solve the maze. The mouse here is show during the third trial of acquisition. We usually get stable asymptotic performance at the end of 5 trials
  23. Passive avoidance
  24. OK, In PA an animal is held in a chamber, the gate opens and the animal is allowed to step down into another chamber, where they receive an averse stimuli. Most people use shock, but we use bright lights and noise. Following just a single encounter trial, animals are subsequently reluctant to step off of the safe platform. The animals’ reluctance to leave the platform is believed to not reflect fear, because typical fear responses are not expressed in animals engaged in the avoidance response (Bolles, 1970;Morris, 1974). The latency, or reluctance to leave the platform after one exposure is used to create a ratio of how well the animal learned the avoidance response. Avoidance responses are very important in humans. We grab the railing every time we go down a flight of stairs, even if we have only fallen once as a toddler.
  25. I will spare you an explanation of the H20 maze.
  26. We use the spatial version of the Morris water maze, were mice most find a non visible platform. As you all know, performance is dependent on the stability of extra-maze cues, or “landmarks”, and is said to reflect the animals’ representation of its environment as a “cognitive map”.
  27. Odor discrimination is a task that most of are subjects excel at.
  28. Animals learn to associate an odor with a food reward. During training the target, rewarded odor randomly shifts. After 2 or three trials, most mice immediately go to the rewarded odor
  29. We use behavioral suppression in are Fear conditioning of mice
  30. Animals learn to associate a tone with shock. Then in a novel environment the tone is introduced during shaped drinking behavior. We use the disruption of drinking as a measurement of learned fear.
  31. Reinforced alternation tests animals pattern recognizing abilities.
  32. Animals are rewarded in one arm of a T maze, and most learn that the arm opposite the last rewarded arm is always the one that is baited. We can get stable performance after 10-12 training trials
  33. The RAM
  34. We’ve included the Radial arm maze as another spatial task. There is such an abundance of literature and so much controversy on rodent spatial skills, that spatial tests have become very important in animal models of general intelligence. As are last speaker, White, pointed out also, animals might use different skills or modals to solve differing spatial problems.. In the Ram, not only most the animal plan were to go to be rewarded, it most remember where it has been…..
  35. The final task we currently use in our battery is a Spatial WIN/Stay test.
  36. The goal in this task stays the same, but the animal is introduced into the maze at different locations, as in the water maze. However in this maze, the motor and stress demands places on our mice are different from swimming. This first trial, you can bearly see, the animal do not know which arm holds the reward. However, after acquisition, most animals go right to the baited arms.
  37. Know, when we run animals through this battery, we see just what one sees in human populations and IQ tests. Animal that perform well in one learning task, during acquisition, perform well in other tasks. For demonstrative purposes, I am going to discuss two animals in a group we ran, 16, a good learning, and 13, a not so good learner, a remedial mouse On the top On the bottom..
  38. In Passive avoidance, larger bars indicate stronger learning. 16 again learns well 13 doesn’t learn anything.
  39. Same in the H2O maze 16…. 13……
  40. Fear conditioning, higher bars represent better learning, 16 learns well 13 isn’t doing so well
  41. What we’ve found in mice in our battery is the same as in human tests of general intelligence and learning abilities, Good performance on one cognitive tests matches with good performance on others. I will spare you the details of factor analysis, But as in humans, our data reveals a large first factor, high correlation btw indiduals performance on one task and performance on another. This first factor represents G or General intelligence influences on a task, with task specific abilities removed. So as in humans, A G factor or a mental engine appears to drive learning abilities.
  42. This is all well and good, but because we use mice, it is possible that something else is driving performance. Exploration in an open field is highly correlated with performance in our battery. If a mouse spends more time in the open stressful areas of an OF, it performs better in the test battery. So is the battery just measuring stress?
  43. It’s possible but the answer so far is ….
  44. NO, Henni has been investigating this possibility and has found, read
  45. Does our battery measure emotionality rather than general intelligence
  46. No Read, Also aversive task, FC, H20, load or are correlated weakly with a general factor, our measure of general intelligent
  47. Our we measuring Novelty seeking or past experience rather than general intelligence
  48. NO, Using pertaining and exploration a novelty seeking, Ken and Lou have been able to ingeniously separate this factors from general learning abilities. Though general intelligence does seem to be related to exploration. This makes sense in mice, since animals that engage their environments are more likely to be exposed to the contingencies that underlie our test battery.
  49. Instead of General intelligence are we measuring variations in WM? This is a fasinated question Complex working memory, not simple digit span, but the ability to hold and manipulate novel information is very similar to definitions of general intelligence. I would love to answer this question for you but
  50. You’ll have to come see Stefan&apos;s talk before the Xmas party.
  51. My focus has mostly been on groups difference in general intelligence and using the battery as a through-put to categorize mice.
  52. SO finally a little about 2 of my favorite topic age and sex: IN Human populations: Age has been associated with a decline in Fluid intelligence However this can be offset by an increase in crystallized intelligence. We all remember how the RW model, but have trouble learning how to work a new digital toaster. Slower (neural conduction velocity) synaptic transmission, reduction in myelin SEX: NO overall difference in IQ Men better at spatial ( however Hampton an cycle), mechanical tasks, females better verbal skills Hedges1995- other two acertions And of course gross morphological differences We wanted to examine how age and/or sex influences learning abilities in mice
  53. Over 3 replications we used……. Read for groups
  54. Our sensory motor tasks included……
  55. Mice were also tested on a wide array of sensory motor tasks. These tests not only quantify sensory/motor function but also emotionality, and stress reactivity. These tests included measures of pain sensitivity, coordination/strength, light/dark preferences and measures of general activity (e.g., running-wheel performance) along with exploratory behavior.
  56. We included 8 learning tasks in this study
  57. We also assessed memory utilizing 3 LTM retention tasks and a working memory task. Ok, IN the learning tasks:
  58. In the majority of our learning tasks we did not see any effects of either age or sex. On this slide I am showing data from our PA and LASHLEY 3 tests Also no differences in Spatial win stay or Reinforced alternation
  59. Like many other before, we found that age impaired h2o performance AXIS = This impairment was NOT due to basal differences in either swim speeds or path lengths to the hidden platform.
  60. Two tasks, ODOR and RAM, old males displayed an impairment , or slower acquisition (PRESS). However, they we able to master the tasks like other groups of mice
  61. FC produced an unusual result Young males appeared to be impaired learning a fear conditioned response. We saw this effect in all three replications. But had no explanation…
  62. What we found was that it was a motivational difference. Young males were thirstier.. The graph on the right shows basal drinking during different acclimation periods. the Young males are, shown in the white bars, drink more, they found the water more rewarding.. This was not a learning impairment, but a performance/motivational effect fortunately we could overcome this motivational problem with extensive training, which was important since FC was used in our retention tests…..
  63. Females not more active in 10 out of 11 tests of activity Only stress difference in PLUS MAZE, females more stressed Learning: H20 alone not a good measure for age differences. Didn’t see impairment in the majority of other tasks No sex difference We did not observe a big drop in LTM or retention due to age in our BALB/C mice Thank you
  64. In 3 of our tasks, mice received ayssimotic training, than 30 days later were tested for retention
  65. These are the results from the LASHLSEY test. We trained animals 2 additional days, than30d later looked at retention, There was some decay, but no differences do to age or sex, There was no decay for any groups in Fear conditioning. Over training created a long lasting fear response.
  66. 30 days after odor training, it appears that there is an age impairment, but if we look at the % increase in errors after 30 days, what we see is less decay in young females. Because of their good performance there is an effect of age, We didn’t see long-term memory difference in any other tasks So We want to duplicate this Odor might not be appropriate for LTM, it doesn&apos;t have high resolution OF course there might be a decay in olfactory abilities in are mice with age.
  67. Explain Males less impaired
  68. Thank you -------- The word Symposium comes from the Greek and literally means “ drinking together”. And it’s always a pleasure to be in the company of some many who retain this classical tradition. Today I’ll be discussing age and sex affect performance in a battery of tests designed to assess general learning abilities