Neural consequences of enviromental enrichment

Nature Reviews Neuroscience

Volumn 1, Issue 3, 2000, Pages 191-198

  van Praag, Henriette ^a   Kempermann, Gerd ^a   Gage, Fred H ^a  

^a SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL; BRAIN; CELL DIVISION; CYTOLOGY; GROWTH, DEVELOPMENT AND AGING; HUMAN; MICROCLIMATE; NERVE CELL PLASTICITY; PHYSIOLOGY; REVIEW; SENSORY DEPRIVATION;

ANIMALS; BRAIN; CELL DIVISION; ENVIRONMENT, CONTROLLED; HUMANS; NEURONAL PLASTICITY; SENSORY DEPRIVATION;

EID: 0034576650     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/35044558     Document Type: Article

References (131)

1. Rosenzweig, M. R. in Development and Evolution of Brain Size 263-293 (Academic Press, 1979).
2. Renner, M. J. & Rosenzweig, M. R. Enriched and Impoverished Environments: Effects on Brain and Behaviour (Springer, New York, 1987).
3. Hebb, D. O. The Organization of Behaviour (Wiley, New York, 1949).
4. Hebb, D. O. The effects of early experience on problem- solving at maturity. Am. Psychol. 2, 306-307 (1947).
5. Wiesel, T. N. & Hubel, D. N. Extent of recovery from the effects of visual deprivation in kittens. J. Neurophysiol. 28, 1060-1072 (1965).
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).
7. Rosenzweig, M. R. Environmental complexity, cerebral change, and behavior. Am. Psychol. 21, 321-332 (1966).
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).
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).
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).
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).
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).
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).
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).
15. Holloway, R. L. Dendritic branching: some preliminary results of training and complexity in rat visual cortex. Brain Res. 2, 393-396 (1966).
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).
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).
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).
19. Greenough, W. T. in Neural Mechanisms of Learning and Memory (eds Rosenzweig, M. R. & Bennett, E. L.) 255-278 (MIT Press, Cambridge, Massachusetts, 1976).
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).
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).
22. Walsh, R. N. & Cummins, R. A. Changes in hippocampal neuronal nuclei in response to environmental stimulation. Int. J. Neurosci. 9, 209-212 (1979).
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).
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).
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).
26. Bernstein, L. A study of some enriching variables in a free- environment for rats. J. Psychosomatic Res. 17, 85-88, (1973).
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).
28. Walsh, R. N. & Cummins, R. A. Mechanisms mediating the production of environmentally induced brain changes. Psychol. Bull. 82, 986-1000 (1975).
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).
30. Ambrogini, P. et al. Spatial learning affects immature granule cell survival in adult rat dentate gyrus. Neurosci. Lett. 286, 21-24 (2000).
31. Gould, E. et al. Learning enhances adult neurogenesis in the hippocampal formation. Nature Neurosci. 2, 260-265 (1999).
32. Greenough, W. T, Cohen, N. J. & Juraska, J. M. New neurons in old brains: learning to survive? Nature Neurosci. 2, 203-205 (1999).
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).
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).
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).
36. Kempermann, G., Kuhn, H. G. & Gage, F. H. Experience- induced neurogenesis in the senescent dentate gyrus. J. Neurosci. 18, 3206-3212 (1998).
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).
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).
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).
40. Altman, J. Are new neurons formed in the brains of adult mammals? Science 135, 1127-1128 (1962).
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).
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).
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).
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).
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).
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).
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).
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).
49. Beaulieu, C. & Colonnier, M. The effect of richness of the environment on cat visual cortex. J. Comp. Neurol. 266, 478-494 (1987).
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).
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).
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).
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).
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).
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).
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).
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).
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).
59. Vanderwolf, C. H. Hippocampal electrical activity and voluntary movement in the rat. Electroencephalogr. Clin. Neurophysiol. 26, 407-418 (1969).
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).
61. Bliss, T. V. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31-39 (1993).
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).
63. Wang, S., Scott, B. W. & Wojtowicz, J. M. Heterogenous properties of dentate granule neurons in adult rat. J. Neurobiol. 42, 248-257 (2000).
64. Calof, A. L. Intrinsic and extrinsic factors regulating vertebrate neurogenesis. Curr Opin. Neurobiol. 5, 19-27 (1995).
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).
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).
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).
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)
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).
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).
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).
72. Young, D. et al. Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nature Med. 5, 448-453 (1999).
73. Carro, E. et al. Circulating insulin-like growth factor I mediates effects of exercise on the brain. J. Neurosci. 20, 2926-2933 (2000).
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).
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).
76. Neeper, S. A., Gomez-Pinilla, F., Choi, J. & Cotman, C. Exercise and brain neurotrophins. Nature 373, 109 (1995).
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).
78. Kang, H. & Schuman, E. M. Long-lasting neurotrophin- induced enhancement of synaptic transmission in the adult hippocampus. Science 267, 1658-1662 (1995).
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).
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).
81. Por, S. B., Bennett, E. L. & Bondy, S. C. Environmental enrichment and neurotransmitter receptors. Behav. Neural Biol. 34, 132-140 (1982).
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).
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).
84. Zolman, J. & Morimoto, H. Cerebral changes related to duration of environmental complexity and locomotor activity. j. Comp. Physiol. Psychol. 60, 382-387 (1965).
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).
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).
87. Soares, J. et al. Brain noradrenergic responses to footshock after chronic activity-wheel running. Behav. Neurosci. 113, 558-566 (1999).
88. Chaouloff, F. Physical exercise and brain monoamines: a review. Acta Physiol. Scand. 137, 1-13 (1989).
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).
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. Madsen T M. et al. Increased neurogenesis in a model of electroconvulsive therapy. Biol. Psychiatry 47, 1043-1049 (2000).
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).
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).
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).
95. Darymple-Alford, J. C. & Benton, D. Preoperative differential housing and dorsal hippocampal lesions in rats. Behav. Neurosci. 98, 23-34 (1984).
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).
97. Johansson, B. B. Functional outcome in rats transferred to an enriched environment 15 days after focal brain ischemia. Stroke 27, 324-326 (1996).
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).
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).
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).
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).
102. Gerlai, R. Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci. 19, 177-181 (1996).
103. Bennet, E. L. et al. Effects of successive environments on brain measures. Physiol. Behav. 12, 621-631 (1974).
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).
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).
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).
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).
108. Horner, P. J. & Gage, F. H. Regenerating the damaged nervous system. Nature 407, 963-970 (2000).
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).
110. Darymple-Alford, J. C. & Benton, D. Preoperative differential housing and dorsal hippocampal lesions in rats. Behav. Neurosci. 98, 23-34 (1984).
111. Gentile, A. M. & Beheshti, Z. Enrichment versus exercise effects on motor impairments following cortical removals in rats. Behav. Neural Biol. 47, 321-332 (1987).
112. Johansson, B. B. Functional outcome in rats transferred to an enriched environment 15 days after focal brain ischemia. Stroke 27, 324-326 (1996).
113. 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).
114. 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).
115. 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).
116. 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).
117. Gerlai, R. Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? Trends Neurosci. 19, 177-181 (1996).
118. Bennet, E. L. et al. Effects of successive environments on brain measures. Physiol. Behav. 12, 621-631 (1974).
119. 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).
120. 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).
121. 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).
122. 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).
123. Horner, P. J. & Gage, F. H. Regenerating the damaged nervous system. Nature 407, 963-970 (2000).
124. 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).
125. 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).
126. 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).
127. Winocur, G. Environmental influences on cognitive decline in aged rats. Neurobiol. Aging 19, 589-597 (1998).
128. 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).
129. 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).
130. 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).
131. Warren, J. M., Zerweck, C. & Anthony, A. Effects of environmental enrichment on old mice. Dev. Psychobiol. 15, 13-18 (1982).