Environmental influences on brain and behaviour

Transcription

1 Environmental influences on brain and behaviour Abdul H. Mohammed Dept. of Neurotec Karolinska Institutet Stockholm, Sweden IBRO African Neuroscience School, Nairobi, 2005

2 Environmental interventions affecting brain and behaviour Enriched environment Physical activity Feeding schedules Early experience (neonatal handling) Light

3 Erisistratus ( BC). Ideas about brain changes in relation to experience. More cerebral folds in intelligent people. M. Malacarne ( ). Experiments with pairs of parrots, finches and dogs. Neuroencefalotomia, Charles Darwin ( ). Differences in brains of domesticated and wild rabbits, pigs, sheep, ducks. Ramón y Cajal ( ). The brain is capable of an education unknown to other organs

4 Donald Hebb ( ) The cell assembly theory Effect of sensory stimulation

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7 Enriched Environment

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11 Enriched rats differed from impoverished rats in: i) Neurone size ii) Dendritic branching iii) Dendritic spine density iv) No. of neurones per synapse v) Size of synapse

12 PRINCIPAL CELLULAR DIFFERENCES IN THE OCCIPITAL CORTEX BETWEEN EC/IC RATS Cellular Variable Environment Reference Neuron Size EC > IC Diamond MC., et al Neuron Density IC > EC Turner A. & Greenough W., 1985 Dendritic Branching EC > IC Vokmar R. &Greenough W, 1972 Dendritic Spine Density EC > IC Globus A., et al Number of Unmyelinated Axons in Splenium of Corpus Callosum Size of Unmyelinated Axons in Splenium of Corpus Callosum EC > IC Juraska JM. & Kopcik JR, 1988 EC > IC - Number of Synapses per Neuron EC > IC Turner A. & Greenough WT., 1985 Size of Synaptic Contact EC > IC West RW. & Greenough WT, 1972 Capillary Vessels EC > IC Black JE., et al Astrocytic Nuclei EC > IC Sirevaag AM. & Greenough WT., 1987 Oligodendrocytic Nuclei EC > IC -

13 Enrichment effects: hippocampus Study Effects Walsh R.N. et al., Hippocampal thickness Fiala BA et al., 1978 Juraska J. et al., 1985, 1989 Granule cells dendrites (young) Dendritic branching (females) Susser ER and Wallace RB, 1982 More granular cells York A. et al., 1989, Kempermann et al., 1997,1988 Mohammed A et al., 1990,1993,2002 Neurogenesis Increased levels: Neurotrophins, GR

14 Regions of persistent neurogenesis in the adult rat brain

15 York AD, Breedlove SM, Diamond MC and Greer ER. Housing adult male rats in enriched conditions increases neurogenesis in the dentate gyrus.. (1989) Soc. Neurosci Abstr,, no

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17 Kempermann G, Kuhn HG and Gage FH. (1997). More hippocampal neurons in adult mice living in an enriched environment.. Nature, 386: York AD, Breedlove SM, Diamond MC and Greer ER. Housing adult male rats in enriched conditions increases neurogenesis in the dentate gyrus.. (1989) Soc. Neurosci Abstr,, no

18 Learning Open-field activity Object exploration Social interaction Behaviour

19 Water maze performance of rats living in EC and IC for 1 year Latency to reach platform (sec) Days Enriched Isolated Long-term enrichment facilitated acquisition of spatial learning task in middle aged rats. *(p < 0,05). T M Pham et al., Neurosci., 1999

20 Open-Field Test

21 M. Renner,, 1987

22 Neurotrophins Structurally and functionally related Important trophic actions on PNS & CNS (Affect neuroplasticity) Nerve Growth Factor (NGF) Brain-derived neurotrophic factor (BDNF) Neurotrophin-3 (NT-3)

23 NGF Levels NGF concentrations (pg/g tissues) * * * Enriched Isolated Hippocampus Visual Cortex Entorhinal Cortex Hypothalamus T M Pham et al., Neuroscience,, 1999

24 ** Hippocampus ** * NGF BDNF NT-3 Enriched Isolated Neurotrophins Levels (ng/g wet tissue)

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27 Environmental stimulation affects brain anatomy, biochemistry and behaviour during: Development Adulthood Ageing

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35 Effects of environmetal enrichment on brain and behaviour have been observed in: fruitflies fish mice rats rabbits monkeys humans

36 Applications of Enrichment Zoos. Improves animals welfare Recovering from brain damage Activity for brain-damaged individual Post operative environment in stroke victims Neocortical graft Improve behaviourally and reduce atrophy Development Education, child rearing Brain ageing - Use it or lose it Enhancing neuronal activity during aging

37 Behavioural interventions affecting brain measures Enriched environment Physical activity Feeding schedules Early experience (neonatal handling)

38 Beneficial effects of exercise Enhances learning Increases neuronal survival and resistance to brain insult Stimulate neurogenesis Maintains cognitive function during aging

39 C. Cotman,, 2002 Seven days of voluntary wheel-running increased BDNF mrna and protein levels in the hippocampus

40 The neurotrophin BDNF Enhances hippocampal synaptic transmission Increased in hippocampus following learning Related to memory performance in aged rats

41 Behavioural interventions affecting brain measures Enriched environment Physical activity Feeding schedules Early experience (neonatal handling)

42 Beneficial effects of restricted feeding Increases longevity in mice Enhances learning Stimulates neurogenesis

43 M. Mattson, 2000

44 DIETARY ACTIVITY, PHYSICAL ACTIVITY Increased Neuronal Activity Production of: Neurotrophic factors Enhanced Proliferation and Survival of Neural Stem Cells RESISTANCE TO AGING AND INJURY ENHANCED SYNAPTIC PLASTICITY M. Mattson, 2001

45 Neuroprotective Signalling and the Aging Brain: Take Away my Food and Let me Run Mark P. Mattson

46 Behavioural interventions affecting brain measures Enriched environment Physical activity Feeding schedules Early experience (neonatal handling)

47 Seymour Levine, 1960 I II III Shock No shock Undisturbed

48 Postnatal Manipulations (1) Early handling (EH): A 3-15 min separation of pups from the dam daily, for 3 weeks Non-handling (NH): Non-handled litters and dams are not exposed to any human contact.

49 Neonatal handling/non handling Earlier eye-opening Higher body weight Develop faster motor coordination Learn better Cope better with stress

50 Corticosterone (ug/100 ml) Minutes Handled Control S. Levine, 1962

51 Meaney et al, Science, 1988 Early handling versus Non-handling and neuron loss during aging Early Handled Non-Handled

52 NGF levels pg/g tissues H NH H-S NH-S Hippocampus Hypothalamus Nonhandled animals had significantly (p<0.05) lower NGF levels as compared to other groups. T. Pham et al, 1989

53 Postnatal Handling The handling of rat pups by humans has a subsequent positive effect on the rats endocrine system and cognitive functioning as adults.. This effect may be due to the intense licking and grooming these handled pups receive by their mothers when they are returned to the homecage.

54 The Importance of a Well- Groomed Child Robert Sapolsky: Personality differences among mother rats Increased maternal licking and grooming Increase in hippocampal GR receptors Better cognitive function and stress-coping

55 Sources of Variance in Genetic Effects behavioural tests Systematic Environmental Treatments Uncontrolled Pre-Test (Rearing) Environmental Effects Idiosyncratic Environmental Effects that Occur During Testing N. Henderson, 2001

56 Idiosyncratic Testing Environment Effects The Bad Day Effect Events that occur prior to and/or during testing that alter test behaviour (eg. a large temperature fluctuation or a disturbance in the colony or testing room)

57 The Clumsy Test Effect Stresses to the animal induced just prior to testing (eg. unusual difficulty extracting the animal from its home cage or in placing it in the test apparatus)

58 The Stinky Apparatus Effect Uncontrolled residual sensory cues in the test apparatus that alters the subject s behaviour

59 The Faulty Scoring Effect Temporary data recording problems, ranging from altered sensitivity of electronic monitoring devices to inattentive observers who are scoring behaviour

60 The Slammed Door Effect Sudden sensory intrusions or disturbances that occur during testing

61 The What do I do now Effect Variations in tester responses to unanticipated actions of the animal being tested (eg. jumping from the apparatus)

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