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Neural consequences of enviromental enrichment

Key Points

  • In the present paper, we focus on neuronal changes that occur in response to complex stimulation by an enriched environment. An enriched environment is 'enriched' in relation to standard laboratory housing conditions. In general the 'enriched' animals are kept in larger cages and in larger groups with tunnels, nesting material and toys.

  • Exposure to an enriched environment has been found to elicit neuroanatomical and behavioural changes, such as enhanced dendritic arborization, gliogenesis, neurogenesis, and improved learning.

  • It is difficult to isolate the behavioural factors that are responsible for neural changes. Factors such as social interaction, learning and motor activity have been suggested to mediate neural consequences of the enriched environment.

  • Similar to the effects of environmental enrichment, voluntary exercise in a running wheel enhances the survival of newborn neurons in the dentate gyrus. In addition, both conditions improve learning and memory. Therefore effects of enrichment and exercise on behavioural, morphological and molecular changes in the brain are compared in the review.

  • Enrichment increases dendritic branching and synaptogenesis in cortex and hippocampus. It is not known if exercise results in similar changes.

  • Exercise enhances dentate gyrus long-term potentiation. Enrichment increases excitatory postsynaptic potential slopes in the dentate gyrus.

  • Both exercise and enrichment enhance production of certain growth factors and neurotransmitters in the hippocampus.

  • Two areas of neurobiological research that may benefit from use of the environmental enrichment and exercise models are mouse genetics and studies of recovery of function following brain and spinal injury or disease. For example, enrichment has been shown to enhance function in mice that have been engineered to overexpress Huntington's disease gene products. In addition, enrichment as well as exercise seem to be beneficial for conditions such as stroke and epilepsy.

Abstract

Neuronal plasticity is a central theme of modern neurobiology, from cellular and molecular mechanisms of synapse formation in Drosophila to behavioural recovery from strokes in elderly humans. Although the methods used to measure plastic responses differ, the stimuli required to elicit plasticity are thought to be activity-dependent. In this article, we focus on the neuronal changes that occur in response to complex stimulation by an enriched environment. We emphasize the behavioural and neurobiological consequences of specific elements of enrichment, especially exercise and learning

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Figure 1: Living conditions in different experimental groups.
Figure 2: Effects of elements of enrichment, such as learning and exercise, on cell proliferation (one day post BrdU exposure) and neurogenesis (four weeks post BrdU exposure) in the dentate gyrus.

References

  1. 1

    Rosenzweig, M. R. in Development and Evolution of Brain Size 263– 293 (Academic Press, 1979).

    Google Scholar 

  2. 2

    Renner, M. J. & Rosenzweig, M. R. Enriched and Impoverished Environments: Effects on Brain and Behaviour (Springer, New York, 1987).A comprehensive review of the early literature (1970–80s) on the neuroanatomical, neurochemical and behavioural consequences of enrichment. It also includes the history of enrichment dating back to Charles Darwin. In addition, the generalizability of effects of enrichment across species is reviewed. The authors identify learning as a critical component of the enriched environment.

    Google Scholar 

  3. 3

    Hebb, D. O. The Organization of Behaviour (Wiley, New York, 1949 ).

    Google Scholar 

  4. 4

    Hebb, D. O. The effects of early experience on problem-solving at maturity. Am. Psychol. 2, 306–307 (1947).

    Google Scholar 

  5. 5

    Wiesel, T. N. & Hubel, D. N. Extent of recovery from the effects of visual deprivation in kittens. J. Neurophysiol. 28, 1060–1072 (1965).

    CAS  PubMed  Google Scholar 

  6. 6

    Hubel, D. N. & Wiesel, T. N. The period of susceptibility to the physiological effects of unilateral eye closure in kittens. J. Physiol. 206, 419–436 (1970).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Rosenzweig, M. R. Environmental complexity, cerebral change, and behavior. Am. Psychol. 21, 321–332 ( 1966).

    CAS  PubMed  Google Scholar 

  8. 8

    Rosenzweig, M. R., Krech, D., Bennett, E. L. & Diamond, M. C. Effects of environmental complexity and training on brain chemistry and anatomy . J. Comp. Physiol. Psychol. 55, 429– 437 (1962).

    CAS  PubMed  Google Scholar 

  9. 9

    Rosenzweig, M. R. & Bennett, E. L. Psychobiology of plasticity: effects of training and experience on brain and behavior. Behav. Brain Res. 78, 57–65 (1996).

    CAS  PubMed  Google Scholar 

  10. 10

    Rosenzweig, M. R. & Bennett, E. L. Effects of differential environments on brain weights and enzyme activities in gerbils, rats, and mice. Dev. Psychobiol. 2, 87– 95 (1969).

    CAS  PubMed  Google Scholar 

  11. 11

    Rosenzweig, M. R., Bennett, E. L. & Diamond, M. C. in Psychopathology of Mental Development. (eds Zubin, J. & Jervis, G.) 45–56 (Grune & Stratton, New York, 1967).

    Google Scholar 

  12. 12

    Bennett, E. L., Rosenzweig, M. R. & Diamond, M. C. Rat brain: effects of environmental enrichment on wet and dry weights. Science 164, 825– 826 (1969).

    Google Scholar 

  13. 13

    Bennett, E. L. in Neural Mechanisms of Learning and Memory (eds Rosenzweig, M. R. & Bennett, E. L) 279–287 (MIT Press, Cambridge, Massachusetts, 1976).

    Google Scholar 

  14. 14

    Cummins, R. A., Walsh, R., Budtz-Olsen, O. E., Konstantinos, T. & Horsfall, C. R. Environmentally-induced changes in the brains of elderly rats. Nature 243, 516–518 (1973).

    CAS  PubMed  Google Scholar 

  15. 15

    Holloway, R. L. Dendritic branching: some preliminary results of training and complexity in rat visual cortex. Brain Res. 2, 393– 396 (1966).

    PubMed  Google Scholar 

  16. 16

    Diamond, M. C. et al. Increases in cortical depth and glia numbers in rats subjected to enriched environment. J. Comp. Neurol. 128, 117–126 (1966).

    CAS  PubMed  Google Scholar 

  17. 17

    Diamond, M. C., Ingham, C. C., Johnson, R. E., Bennett, E. L. & Rosenzweig, M. R. Effects of environment on morphology of rat cerebral cortex and hippocampus. J. Neurobiol. 7, 75–85 (1976 ).

    CAS  PubMed  Google Scholar 

  18. 18

    Greenough, W. T. & Volkmar, F. R. Pattern of dendritic branching in occipital cortex of rats reared in complex environments . Exp. Neurol. 40, 491– 504 (1973).

    CAS  PubMed  Google Scholar 

  19. 19

    Greenough, W. T. Neural Mechanisms of Learning and Memory (eds Rosenzweig, M. R. & Bennett, E. L.) 255–278 (MIT Press, Cambridge, Massachusetts, 1976).Discusses similarities between enrichment and learning on brain and behaviour. In addition, changes in synaptic size and dendritic branching in response to enrichment are reviewed in detail.

    Google Scholar 

  20. 20

    Greenough, W. T., West, R. W. & DeVoogd, T. J. Postsynaptic plate perforations: changes with age and experience in the rat. Science 202, 1096–1098 (1978).

    CAS  PubMed  Google Scholar 

  21. 21

    Walsh, R. N., Budtz-Olsen, O. E., Penny, J. E. & Cummins, R. A. The effects of environmental complexity on the histology of the rat hippocampus . J. Comp. Neurol. 137, 361– 366 (1969).

    CAS  PubMed  Google Scholar 

  22. 22

    Walsh, R. N. & Cummins, R. A. Changes in hippocampal neuronal nuclei in response to environmental stimulation. Int. J. Neurosci. 9, 209–212 ( 1979).

    CAS  PubMed  Google Scholar 

  23. 23

    Altman, J. & Das, G. D. Autoradiographic examination of the effects of enriched environment on the rate of glial multiplication in the adult rat brain. Nature 204, 1161– 1163 (1964).Investigated whether enrichment could add new neurons to the adult brain. The focus of the paper was on cortex rather than hippocampus and no new neurons were observed in response to environmental changes. Subsequent studies focused on structural changes in existing cells in response to enrichment.

    CAS  PubMed  Google Scholar 

  24. 24

    Kempermann, G., Kuhn, H. G. & Gage, F. H. More hippocampal neurons in adult mice living in an enriched environment. Nature 386, 493– 495 (1997).The first paper to show that enrichment increases the survival of newborn cells in the dentate gyrus of the hippocampus in adult mice. Enriched mice had 57% more BrdU-positive cells per dentate gyrus than controls. Cell proliferation, however, was not affected.

    CAS  PubMed  Google Scholar 

  25. 25

    Rosenzweig, M. R., Bennett, E. L., Hebert, M. & Morimoto, H. Social grouping cannot account for cerebral effects of enriched environments . Brain Res. 153, 563–576 (1978).

    CAS  PubMed  Google Scholar 

  26. 26

    Bernstein, L. A study of some enriching variables in a free-environment for rats. J. Psychosomatic Res. 17, 85–88, (1973).

    CAS  Google Scholar 

  27. 27

    Ferchmin, P. A. & Bennett, E. L. Direct contact with enriched environment is required to alter cerebral weights in rats. J. Comp. Physiol. Psychol. 88, 360– 367 (1975).

    CAS  PubMed  Google Scholar 

  28. 28

    Walsh, R. N. & Cummins, R. A. Mechanisms mediating the production of environmentally induced brain changes. Psychol. Bull. 82, 986–1000 (1975).

    CAS  PubMed  Google Scholar 

  29. 29

    Van Praag, H., Kempermann, G. & Gage, F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nature Neurosci. 2, 266–270 (1999). Studied the effects of components of the enriched environment such as learning and motor activity on neurogenesis. No effect of learning was observed. However, this is the first study to show that voluntary activity on a wheel increases cell proliferation and survival in the dentate gyrus.

    CAS  PubMed  Google Scholar 

  30. 30

    Ambrogini, P. et al. Spatial learning affects immature granule cell survival in adult rat dentate gyrus. Neurosci. Lett. 286, 21–24 (2000).

    CAS  PubMed  Google Scholar 

  31. 31

    Gould, E. et al. Learning enhances adult neurogenesis in the hippocampal formation . Nature Neurosci. 2, 260– 265 (1999).

    CAS  PubMed  Google Scholar 

  32. 32

    Greenough, W. T., Cohen, N. J. & Juraska, J. M. New neurons in old brains: learning to survive? Nature Neurosci. 2, 203–205 (1999).

    CAS  PubMed  Google Scholar 

  33. 33

    Lemaire, V., Koehl, M., Le Moal, M. & Abrous, D. N. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc. Natl Acad. Sci. USA 97, 11032–11037 (2000).

    CAS  PubMed  Google Scholar 

  34. 34

    Pacteau, C., Einon, D. & Sinden, J. Early rearing environment and dorsal hippocampal ibotenic acid lesions: long-term influences on spatial learning and alternation in the rat. Behav. Brain Res. 34, 79– 96 (1989).

    CAS  PubMed  Google Scholar 

  35. 35

    Wainwright, P. E. et al. Effects of environmental enrichment on cortical depth and Morris-maze performance in B6D2F2 mice exposed prenatally to ethanol. Neurotoxicol. Teratol. 15, 11–20 (1993).

    CAS  PubMed  Google Scholar 

  36. 36

    Kempermann, G., Kuhn, H. G. & Gage, F. H. Experience-induced neurogenesis in the senescent dentate gyrus. J. Neurosci. 18, 3206– 3212 (1998).

    CAS  PubMed  Google Scholar 

  37. 37

    Fordyce, D. E. & Farrar, R. P. Enhancement of spatial learning in F344 rats by physical activity and related learning-associated alterations in hippocampal and cortical cholinergic functioning. Behav. Brain Res. 46, 123–133 (1991).

    CAS  PubMed  Google Scholar 

  38. 38

    Fordyce, D. E. & Wehner, J. M. Physical activity enhances spatial learning performance with an associated alteration in hippocampal protein kinase C activity in C57BL/6 and DBA/2 mice. Brain Res. 619, 111–119 ( 1993).

    CAS  PubMed  Google Scholar 

  39. 39

    Van Praag, H., Christie, B. R., Sejnowski, T. J. & Gage, F. H. Running enhances neurogenesis, learning and long-term potentiation in mice . Proc. Natl Acad. Sci. USA 96, 13427– 13431 (1999).

    CAS  PubMed  Google Scholar 

  40. 40

    Altman, J. Are new neurons formed in the brains of adult mammals? Science 135, 1127–1128 ( 1962).

    CAS  PubMed  Google Scholar 

  41. 41

    Szeligo, F. & Leblond, C. P. Response of three main types of glial cells of cortex and corpus callosum in rats handled during suckling or exposed to enriched, control, or impoverished environments following weaning . J. Comp. Neurol. 172, 247– 264 (1977).

    CAS  PubMed  Google Scholar 

  42. 42

    Kempermann, G., Kuhn, H. G. & Gage, F. H. Genetic influence on neurogenesis in the dentate gyrus of adult mice. Proc. Natl Acad. Sci. USA 94, 10409–10414 (1997).

    CAS  PubMed  Google Scholar 

  43. 43

    Kempermann, G., Brandon, E. P. & Gage, F. H. Environmental stimulation of 129/SvJ mice results in increased cell proliferation and neurogenesis in the adult dentate gyrus . Curr. Biol. 8, 939–942 (1998).

    CAS  PubMed  Google Scholar 

  44. 44

    Altman, J., Wallace, R. B., Anderson, W. J. & Das, G. D. Behaviorally induced changes in length of cerebrum in rat. Dev. Psychobiol. 1, 112–117 ( 1968).

    Google Scholar 

  45. 45

    Diamond, M. C., Lindner, B. & Raymond, A. Extensive cortical depth measurements and neuron size increases in the cortex of environmentally enriched rats. J. Comp. Neurol. 131, 357–364 ( 1967).

    Google Scholar 

  46. 46

    Volkmar, F. R. & Greenough, W. T. Rearing complexity affects branching of dendrites in the visual cortex of the rat. Science 176, 1445–1447 ( 1972).

    CAS  PubMed  Google Scholar 

  47. 47

    Globus, A., Rosenzweig, M. R., Bennett, E. L. & Diamond, M. C. Effects of differential environments on dendritic spine counts. J. Comp. Phys. Psych. 84, 598–604 (1973).

    Google Scholar 

  48. 48

    Bhide, P. G. & Bedi, K. S. The effects of a lengthy period of environmental diversity of well-fed and previously undernourished rats. II. Synapse to neurons ratios. J. Comp. Neurol. 227 , 305–310 (1984).

    CAS  PubMed  Google Scholar 

  49. 49

    Beaulieu, C. & Colonnier, M. The effect of richness of the environment on cat visual cortex. J. Comp. Neurol. 266, 478–494 (1987).

    CAS  PubMed  Google Scholar 

  50. 50

    Juraska, J. M., Fitch, J. M., Henderson, C. & Rivers, N. Sex differences in the dendritic branching of dentate granule cells following differential experience. Brain Res. 333, 73–80 (1985).

    CAS  PubMed  Google Scholar 

  51. 51

    Altschuler, R. A. Morphometry of the effect of increased experience and training on synaptic density in area CA3 of the rat hippocampus. J. Histochem. Cytochem. 27, 1548–1550 ( 1979).

    CAS  PubMed  Google Scholar 

  52. 52

    Rampon, C. et al. Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice. Nature Neurosci. 3, 205–206 (2000).

    Google Scholar 

  53. 53

    Kleim, J. A., Lussnig, E., Schwarz, E. R., Comery, T. A. & Greenough, W. T. Synaptogenesis and FOS expression in the motor cortex of the adult rat after motor skill learning . J. Neurosci. 16, 4529– 4535 (1996).

    CAS  PubMed  Google Scholar 

  54. 54

    Black, J. E. Isaacs, K. R., Anderson, B. J., Alcantara, A. A. & Greenough, W. T. Leaning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc. Natl Acad. Sci. USA 87, 5568–5572 (1990).

    CAS  PubMed  Google Scholar 

  55. 55

    Isaacs, K. R., Anderson, B. J., Alcantara, A. A., Black, J. E. & Greenough, W. T. Exercise and the brain: angiogenesis in the adult rat cerebellum after vigorous physical activity and motor skill learning. J. Cereb. Blood Flow Metab. 12, 110–119 (1992).

    CAS  PubMed  Google Scholar 

  56. 56

    Green, E. J. & Greenough, W. T. Altered synaptic transmission in dentate gyrus of rats reared in complex environments: evidence from hippocampal slices maintained in vitro. J. Neurophysiol. 55, 739–750 (1986).

    CAS  PubMed  Google Scholar 

  57. 57

    Foster, T. C., Fugger, H. N. & Cunningham, S. G. Receptor blockade reveals a correspondence between hippocampal-dependent behavior and experience-dependent synaptic enhancement . Brain Res. 871, 39–43 (2000).

    CAS  PubMed  Google Scholar 

  58. 58

    Sharp, P. E., McNaughton, B. L. & Barnes, C. A. Enhancement of hippocampal field potentials in rats exposed to a novel, complex environment. Brain Res. 339, 361–365 (1985).

    CAS  PubMed  Google Scholar 

  59. 59

    Vanderwolf, C. H. Hippocampal electrical activity and voluntary movement in the rat. Electroencephalogr. Clin. Neurophysiol. 26, 407– 418 (1969).

    CAS  PubMed  Google Scholar 

  60. 60

    Czurko, A., Hirase, H., Csicsvari, J. & Buzsaki, G. Sustained activation of hippocampal pyramidal cells by 'space clamping' in a running wheel. Eur. J. Neurosci. 11, 344 –352 (1999).

    CAS  PubMed  Google Scholar 

  61. 61

    Bliss, T. V. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361 , 31–39 (1993).

    CAS  PubMed  Google Scholar 

  62. 62

    Bronzino, J. D. et al. Maturation of long-term potentiation in the hippocampal dentate gyrus of the freely moving rat. Hippocampus 4, 439–446 (1994).

    CAS  PubMed  Google Scholar 

  63. 63

    Wang, S., Scott, B. W. & Wojtowicz, J. M. Heterogenous properties of dentate granule neurons in adult rat. J. Neurobiol. 42, 248– 257 (2000).

    CAS  PubMed  Google Scholar 

  64. 64

    Calof, A. L. Intrinsic and extrinsic factors regulating vertebrate neurogenesis. Curr. Opin. Neurobiol. 5, 19–27 (1995).

    CAS  PubMed  Google Scholar 

  65. 65

    Aberg, M. A. I. et al. Peripheral infusion of IGF-1 selectively induces neurogenesis in the adult rat hippocampus. J. Neurosci. 20, 2896–2903 (2000).

    CAS  PubMed  Google Scholar 

  66. 66

    Kuhn, H. G., Winkler, J., Kempermann, G., Thal, L. J. & Gage, F. H. Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J. Neurosci. 17, 5820– 5829 (1997).

    CAS  PubMed  Google Scholar 

  67. 67

    Wagner, J. P., Black, I. B. & DiCicco-Bloom, E. Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor. J. Neurosci. 19, 6006–6016 (1999).

    CAS  PubMed  Google Scholar 

  68. 68

    Rasika, S., Alvarez-Buylla, A. & Nottebohm, F. BDNF mediates the effects of testosterone on the survial of new neurons in an adult brain. Neuron 22, 53–62 (1999).

    CAS  PubMed  Google Scholar 

  69. 69

    Mohammed, A. H. et al. Environmental influences on the central nervous system and their implications for the aging rat. J. Brain Res. 57, 183–191 (1993).

    CAS  Google Scholar 

  70. 70

    Pham, T. M. et al. Changes in brain nerve growth factor levels and nerve growth factor receptors in rats exposed to environmental enrichment for one year . Neuroscience 94, 279– 286 (1999).

    CAS  PubMed  Google Scholar 

  71. 71

    Falkenberg, T. et al. Increased expression of brain-derived neurotrophic factor mRNA in rat is associated with improved spatial memory and enriched environment . Neurosci. Lett. 138, 153– 156 (1992).

    CAS  PubMed  Google Scholar 

  72. 72

    Young, D. et al. Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nature Med. 5, 448–453 (1999).

    CAS  PubMed  Google Scholar 

  73. 73

    Carro, E. et al. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J. Neurosci. 20, 2926–2933 (2000).

    CAS  PubMed  Google Scholar 

  74. 74

    Gomez-Pinilla, F., Dao, L. & Vannarith, S. Physical exercise induces FGF-2 and its mRNA in the hippocampus. Brain Res. 764, 1– 8 (1997).

    CAS  PubMed  Google Scholar 

  75. 75

    Gomez-Pinilla, F., So, V. & Kesslak, J. P. Spatial learning and physical activity contribute to the induction of fibroblast growth factor: neural substrates for increased cognition associated with exercise. Neuroscience 85, 53–61 (1998).

    CAS  PubMed  Google Scholar 

  76. 76

    Neeper, S. A., Gomez-Pinilla, F., Choi, J. & Cotman, C. Exercise and brain neurotrophins. Nature 373, 109 (1995).The first paper to indicate that growth factors may mediate the beneficial effects of exercise on the brain. Specifically, voluntary exercise in rats increased levels of BDNF mRNA in hippocampus and cortex.

    CAS  PubMed  Google Scholar 

  77. 77

    Widenfalk, J., Olson, L. & Thoren, P. Deprived of habitual running, rats downregulate BDNF and TrkB messages in the brain. Neurosci. Res. 34, 125–132 (1999).

    CAS  PubMed  Google Scholar 

  78. 78

    Kang, H. & Schuman, E. M. Long-lasting neurotrophin-induced enhancement of synaptic transmission in the adult hippocampus. Science 267, 1658–1662 ( 1995).

    CAS  PubMed  Google Scholar 

  79. 79

    Figurov, A., Pozzo-Miller, L. D., Olafsson, P., Wang, T. & Lu, B. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature 381, 706–709 ( 1996).

    CAS  PubMed  Google Scholar 

  80. 80

    Fischer, W. et al. Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor. Nature 329, 65–68 (1987).

    CAS  PubMed  Google Scholar 

  81. 81

    Por, S. B., Bennett, E. L. & Bondy, S. C. Environmental enrichment and neurotransmitter receptors . Behav. Neural Biol. 34, 132– 140 (1982).

    CAS  PubMed  Google Scholar 

  82. 82

    Rasmuson, S. et al. Environmental enrichment selectively increases 5-HT1A receptor mRNA expression and binding in the rat hippocampus. Brain Res. Mol Brain Res. 53, 285–290 (1998).

    CAS  PubMed  Google Scholar 

  83. 83

    Krech, D., Rosenzweig, M. R. & Bennet, E. L. Effects of environmental complexity and training on brain chemistry. J. Comp. Physiol. Psychol. 53, 509–515 (1960).

    CAS  PubMed  Google Scholar 

  84. 84

    Zolman, J. & Morimoto, H. Cerebral changes related to duration of environmental complexity and locomotor activity. J. Comp. Physiol. Psychol. 60, 382–387 ( 1965).

    CAS  PubMed  Google Scholar 

  85. 85

    Fordyce, D. E. & Farrar, R. P. Physical activity effects on hippocampal and parietal cortical cholinergic function and spatial learning in F344 rats. Behav. Brain Res. 43, 115–123 (1991).

    CAS  PubMed  Google Scholar 

  86. 86

    Sforzo, G. A., Seeger, T. F., Pert, C. B., Pert, A. & Dotson, C. O. In vivo opioid receptor occupation in the rat brain following exercise. Med. Sci. Sports Exerc. 18, 380–384 ( 1986).

    CAS  PubMed  Google Scholar 

  87. 87

    Soares, J. et al. Brain noradrenergic responses to footshock after chronic activity-wheel running. Behav. Neurosci. 113, 558– 566 (1999).

    CAS  PubMed  Google Scholar 

  88. 88

    Chaouloff, F. Physical exercise and brain monoamines: a review. Acta Physiol. Scand. 137, 1–13 ( 1989).

    CAS  PubMed  Google Scholar 

  89. 89

    Dawirs, R. R., Hildebrandt, K. & Teuchert-Noodt, G. Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus. J. Neural Transm. 105, 317–327 (1998).

    CAS  PubMed  Google Scholar 

  90. 90

    Malberg, J. E. et al. Chronic antidepressant administration increases granule cell genesis in the hippocampus of the adult male rat. J. Neurosci. (in the press).

  91. 91

    Madsen T. M. et al. Increased neurogenesis in a model of electroconvulsive therapy . Biol. Psychiatry 47, 1043– 1049 (2000).

    CAS  PubMed  Google Scholar 

  92. 92

    Brezun, J. M. & Daszuta, A. Serotonergic reinnervation reverses lesion-induced decreases in PSA-NCAM labeling and proliferation of hippocampal cells in adult rats. Hippocampus 10, 37– 46 (2000).

    CAS  PubMed  Google Scholar 

  93. 93

    Brezun, J. M. & Daszuta, A. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats . Neuroscience 89, 999– 1002 (1999).

    CAS  PubMed  Google Scholar 

  94. 94

    Will, B. E., Rosenzweig, M. R., Bennett, E. L., Hebert, M. & Morimoto, H. A relatively brief environmental enrichment aids recovery of learning capacity and alters brain measures after postweaning brain lesions in rats. J. Comp. Physiol. Psych. 91, 33–50 (1977). An important study of the effects of enrichment on recovery from brain lesions. Issues related to the age of the animal at time of injury and the amount of enrichment needed for therapeutic purposes were investigated. The authors found that enrichment of two hours a day was as beneficial as 24 hours a day.

    CAS  Google Scholar 

  95. 95

    Darymple-Alford, J. C. & Benton, D. Preoperative differential housing and dorsal hippocampal lesions in rats. Behav. Neurosci. 98, 23–34 ( 1984).

    Google Scholar 

  96. 96

    Gentile, A. M. & Beheshti, Z. Enrichment versus exercise effects on motor impairments following cortical removals in rats . Behav. Neural Biol. 47, 321– 332 (1987).

    CAS  PubMed  Google Scholar 

  97. 97

    Johansson, B. B. Functional outcome in rats transferred to an enriched environment 15 days after focal brain ischemia. Stroke 27, 324 –326 (1996).

    CAS  PubMed  Google Scholar 

  98. 98

    Stummer, W., Weber, K., Tranmer, B., Baethmann, A. & Kempski, O. Reduced mortality and brain damage after locomotor activity in gerbil forebrain ischemia. Stroke 25, 1862–1869 (1994).

    CAS  PubMed  Google Scholar 

  99. 99

    Stummer, W., Baethmann, A., Murr, R., Schurere, L. & Kempski, O. S. Cerebral protection against ischemia by locomotor activity in gerbils: underlying mechanisms. Stroke 26, 1423–1430 (1995).

    CAS  PubMed  Google Scholar 

  100. 100

    Johansson, B. B. & Ohlsson, A. Environment, social interaction, and physical activity as determinants of functional outcome after cerebral infarction in the rat. Exp. Neurol. 139, 322–327 (1996).

    CAS  PubMed  Google Scholar 

  101. 101

    van Dellen, A., Blakemore, C., Deacon, R., York, D. & Hannan, A. J. Delaying the onset of Huntington's in mice. Nature 404, 721– 722 (2000).

    CAS  PubMed  Google Scholar 

  102. 102

    Gerlai, R. Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci. 19, 177– 181 (1996).

    CAS  PubMed  Google Scholar 

  103. 103

    Bennet, E. L. et al. Effects of successive environments on brain measures. Physiol. Behav. 12, 621–631 (1974).

    Google Scholar 

  104. 104

    Kempermann, G. & Gage, F. H. Experience-dependent regulation of adult hippocampal neurogenesis: effects of long-term stimulation and stimulus withdrawal. Hippocampus 9, 321–332 (1999).

    CAS  PubMed  Google Scholar 

  105. 105

    Brasted, P. J., Watts, C., Robbins, T. W. & Dunnett, S. B. Associative plasticity in striatal transplants. Proc. Natl Acad. Sci. USA 96, 10524–10529 (1999).

    CAS  PubMed  Google Scholar 

  106. 106

    Belanger, M., Drew, T., Provencher, J. & Rossilong, S. A comparison of locomotion in adult cats before and after spinal transection. J. Neurophys. 76, 471–491 (1996).

    CAS  Google Scholar 

  107. 107

    de Leon, R. D., Hodgson, J. A., Roy, R. R. & Edgerton, V. R. Retention of hindlimb stepping ability in adult spinal cats after the cessation of step training. J. Neurophysiol. 81, 85 –94 (1999).

    CAS  PubMed  Google Scholar 

  108. 108

    Horner, P. J. & Gage, F. H. Regenerating the damaged nervous system. Nature 407, 963– 970 (2000).

    CAS  PubMed  Google Scholar 

  109. 109

    Barnea, A. & Nottebohm, F. Seasonal recruitment of hippocampal neurons in adult free-ranging black-capped chickadees. Proc. Natl Acad. Sci. USA 91, 11217–11221 (1994).Suggests a correlation between neurogenesis and the formation of new memories in birds. Subsequent work in mammals has supported this hypothesis.

    CAS  PubMed  Google Scholar 

  110. 110

    Barnea, A. & Nottebohm, F. Recruitment and replacement of hippocampal neurons in young and adult chickadees: an addition to the theory of hippocampal learning. Proc. Natl Acad. Sci. USA 93, 714–718 (1996).

    CAS  PubMed  Google Scholar 

  111. 111

    Levine, S. Infantile experience and resistance to physiological stress. Science 126, 405–406 ( 1957).

    CAS  PubMed  Google Scholar 

  112. 112

    Meaney, M. J., Aitken, D. H., van Berkel, C., Bhatnagar, S. & Sapolsky, R. M. Effect of neonatal handling on age-related impairments associated with the hippocampus. Science 239, 766–768 ( 1988).

    CAS  PubMed  Google Scholar 

  113. 113

    Meaney, M. J. et al. The effects of neonatal handling on the development of the adrenocortical response to stress: implications for neuropathology and cognitive deficits in later life. Psychoneuroendocrinology 16 , 85–103 (1991).

    CAS  PubMed  Google Scholar 

  114. 114

    Francis, D. D. & Meaney, M. J. Maternal care and the development of stress responses. Curr. Opin. Neurobiol. 9, 128–134 ( 1999).

    CAS  PubMed  Google Scholar 

  115. 115

    Liu, D., Diorio, J., Day, J. C., Francis, D. D. & Meaney, M. J. Maternal care, hippocampal synaptogenesis and cognitive development in rats. Nature Neurosci. 3, 799–806 (2000).

    CAS  PubMed  Google Scholar 

  116. 116

    Kuhn, C. M., Butler, S. R. & Schanberg, S. M. Selective depression of serum growth hormone during maternal deprivation in rat pups. Science 201, 1034–1036 (1978).

    CAS  PubMed  Google Scholar 

  117. 117

    Plotsky, P. M. & Meaney, M. J. Early postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in rats. Mol. Brain Res. 18, 195–200 (1993).

    CAS  PubMed  Google Scholar 

  118. 118

    Oitzl, M. S., Workel, J. O., Fluttert, M., Frosch, F. & DeKloet, E. R. Maternal deprivation affects behaviour from youth to senescence: amplification of individual differences in spatial learning and memory in senescent Brown Norway rats. Eur. J. Neurosci. 12, 3771–3780 (2000).

    CAS  PubMed  Google Scholar 

  119. 119

    Hofer, M. A. On the nature and consequences of early loss. Psychosomatic Med. 58, 570–581 ( 1996).

    CAS  Google Scholar 

  120. 120

    Hamm, R. J. Temple, M. D., O'Dell, D. M., Pike, B. R. & Lyeth, B. G. Exposure to environmental complexity promotes recovery of cognitive function after traumatic brain injury. J. Neurotrauma 13, 41–47 (1996).

    CAS  PubMed  Google Scholar 

  121. 121

    Kolb, B. & Gibb, R. Environmental enrichment and cortical injury: behavioral and anatomical consequences of frontal cortex lesions. Cereb. Cortex 1, 189–198 (1991).

    CAS  PubMed  Google Scholar 

  122. 122

    Dahlqvist, P. et al. Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats. Neuroscience 93, 527–535 (1999).

    CAS  PubMed  Google Scholar 

  123. 123

    Zhao, L. R., Mattsson, B. & Johansson, B. B. Environmental influence on brain-derived neurotrophic factor messenger RNA expression after middle cerebral artery occlusion in spontaneously hypertensive rats. Neuroscience 97, 177–184 (2000).

    CAS  PubMed  Google Scholar 

  124. 124

    Soffie, M., Hahn, K., Terao, E. & Eclancher, F. Behavioural and glial changes in old rats following environmental enrichment. Behav. Brain Res. 101, 37–49 (1999).

    CAS  PubMed  Google Scholar 

  125. 125

    Winocur, G. Environmental influences on cognitive decline in aged rats. Neurobiol. Aging 19, 589–597 ( 1998).

    CAS  PubMed  Google Scholar 

  126. 126

    Nakamura, H., Kobayashi, S., Ohashi, Y. & Ando, S. Age-changes of brain synapses and synaptic plasticity in response to an enriched environment . J. Neurosci. Res. 56, 307– 315 (1999).

    CAS  PubMed  Google Scholar 

  127. 127

    Widman, D. R., Abrahamsen, G. C. & Rosellini, R. A. Environmental enrichment: the influences of restricted daily exposure and subsequent exposure to uncontrollable stress. Physiol. Behav. 51, 309–318 (1992).

    CAS  PubMed  Google Scholar 

  128. 128

    Rema, V. & Ebner, F. F. Effect of enriched environment rearing on impairments in cortical excitability and plasticity after prenatal alcohol exposure. J. Neurosci. 19, 10993 –11006 (1999).

    CAS  PubMed  Google Scholar 

  129. 129

    Warren, J. M., Zerweck, C. & Anthony, A. Effects of environmental enrichment on old mice. Dev. Psychobiol. 15, 13–18 (1982).

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the reviewers for their helpful comments on our paper. We appreciate the editorial assistance of M. L. Gage and the assistance of L. Kitabayashi in preparation of the figures. We are grateful for the continued support of the Christopher Reeve Paralysis Foundation, The Lookout Fund, The Parkinson's Disease Foundation and the National Institutes of Health.

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van Praag, H., Kempermann, G. & Gage, F. Neural consequences of enviromental enrichment. Nat Rev Neurosci 1, 191–198 (2000). https://doi.org/10.1038/35044558

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