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Matzel Lab

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Dec3 a

  1. 1. Age and Sex Influences on Crystallized, Fluid, andGeneral 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. 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. 3. Age and Sex Influences on Crystallized, Fluid, andGeneral Intelligence in Mice David A Townsend Department of Psychology Rutgers University
  4. 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 abstractproblems, to see relationships” ( Cattell)
  5. 5. “ the ability to solve novel abstractproblems, 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. 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. 7. Age and Sex Influences on Fluid, and General Intelligence in Mice David A. Townsend Department of Psychology Rutgers University
  8. 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. 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. 10. General IntelligenceA. 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. 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. 12. Group Differences in General Intelligence Individual Differences in General Intelligence
  13. 13. Group Differences in General IntelligenceExperimental Psychology Differences between group meansNormal vs. Disease stateWildtype vs. Knockouts
  14. 14. Individual differences in General Intelligence Differential PsychologyVariation amongst individuals Nature vs. Nurture Molecular mechanisms of intelligence
  15. 15. Age and Sex Influences onGeneral Intelligence in Mice David A. Townsend Department of Psychology Rutgers University
  16. 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. 17. The Efficacy of Synaptic Transmission Between SensoryReceptors Predicts the Capacity for Behavioral Learning inIndividual Animals
  18. 18. A “general” influence on humanintelligence test performance isthe single most dominantcognitive trait ever identified. Robert Plomin, Nature, 1999
  19. 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. 20. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 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. 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 riceDiscrimination (+) 5. Fear association- auditory suppression water foot shockConditioning formation (-)6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory7. 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 (+)
  22. 22. Lashley III Maze
  23. 23. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 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. 24. Passive Avoidance Step Down: Pre/Post
  25. 25. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 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. 26. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 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 (+)
  27. 27. Odor Discriminationtarget DistracterDistracter
  28. 28. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 5. Fear association- auditory suppression water foot shockConditioning 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 (+)
  29. 29. LeDoux
  30. 30. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 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 (+)
  31. 31. Trace Eyeblink Conditioning (Hippocampal-Dependent) 500 ms 250 ms CS (83 db white noise) 100 ms US(0.7 mA periorbital shock)
  32. 32. Reinforced Alternation
  33. 33. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 5. Fear association- auditory suppression water foot shock Conditioning formation (-) 6. Reinforced pattern recognition Prior ambulation water cereal Alternation choice / (+) memory7. 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 (+)
  34. 34. Radial Arm Maze
  35. 35. Test Motor Organic Process Reinforcer Stimulus Requirement Deprivation1. 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 riceDiscrimination (+) 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
  36. 36. Spatial Win/Stay in a Plus Maze START GOAL
  37. 37. Relative Performanceand Average Ranks (Ss9-16) Exemplars: Ss13, Ss16
  38. 38. One-Trial Passive Avoidance
  39. 39. Spatial Water Maze
  40. 40. Associative Fear Conditioning
  41. 41. Good/Poor Learners
  42. 42. PRINCIPAL COMPONENT EXTRACTION Loadings Large First Factor: Lashley Maze .50 Passive Avoidance .68 Odor Discrimination .32 Fear Conditioning .30Evidence 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
  43. 43. Disassociations with General Intelligence Stress Reactivity Fear and Emotionality Experience and Novelty Seeking Working Memory
  44. 44. 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.
  45. 45. 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
  46. 46. Disassociations with General Intelligence Stress Reactivity Fear and Emotionality Experience and Novelty Seeking Working Memory
  47. 47. 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
  48. 48. Disassociations of General Intelligence Stress Reactivity Fear and Emotionality Experience and Novelty Seeking Working Memory
  49. 49. 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
  50. 50. Is General Intelligence Dependent on the Efficacy of WM? Stress Reactivity Fear and Emotionality Experience and Novelty Seeking Working Memory
  51. 51. 12/17/04
  52. 52. Group Differences in General Intelligence Knockout/Heterozygous/ Wildtype  PEA-15  NrCamAge and Sex  ADHD  Personality types
  53. 53. 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
  54. 54. 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
  55. 55. Methods: Sensory/Motor task:11 measures of behavioral fitness12 measures of activity10+ measures of stress reactivity6 motivational measures 8 Learning Tasks: 4 Memory Tasks: one STM, two LTM
  56. 56. 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
  57. 57. Methods: Sensory/Motor task:11 measures of behavioral fitness12 measures of activity10+ measures of stress reactivity6 motivational measures 8 Learning Tasks: 4 Memory Tasks: one STM, two LTM
  58. 58. Methods: Sensory/Motor task:11 measures of behavioral fitness12 measures of activity10+ measures of stress reactivity6 motivational measures 8 Learning Tasks: 4 Memory Tasks: one WM, two LTM
  59. 59. Learning tasks results: Lashley 3 maze Passive avoidance 25 4 20 Young Females Young Males Aged Females 3 15 Aged Males ErrorsRatio (Post/Pre) 10 2 5 1 0 1 2 3 4 5 0 Trial
  60. 60. 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
  61. 61. 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 6.5Latency (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
  62. 62. 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 3Errors 15 2 10 1 5 0 1 2 3 4 5 24h 6 7 8 9 10 0 1 2 3 4 5 Trials
  63. 63. 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
  64. 64. Learning tasks results: Fear conditioning 4 Young Females Young Males Aged Females 3 Aged MalesRatio( Post/Pre) 2 1 0
  65. 65. Learning tasks results: Fear conditioning 4 12 3 Fear asymptotic training Licks8during fear training training trialsRatio( 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
  66. 66. 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
  67. 67. 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 .061637Average 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
  68. 68. Why were the expected groups differences not observed? Inbred Mice (clones) Mortality selection of aged mice (NIA mice) Balb/c (blood work)
  69. 69. Matzel Lab:
  70. 70.  Our Knowledge and expertise may be domain-specific, but the means by which we become knowledgeable and expert may be entirely general (Mackintosh 1998)
  71. 71. Memory tasks: Long Term Memory: Odor discrimination (30 days) Lashley 3 maze (30 days) Fear c Working Memory: RAM delay (120s)
  72. 72. 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 differencesErrors 6 4 2 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 30d A B C Trial
  73. 73. 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 4errors 300 2 200 100 0 0 1 2 3 4 30 Days 5 trial Females Males OLD F OLD M
  74. 74. 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
  75. 75. 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
  76. 76. Hormonal and Sex Differences Have No Effect on Water Maze Preformance Performance OVXMean+ 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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