Elsevier

Neuropharmacology

Volume 47, Issue 5, October 2004, Pages 649-660
Neuropharmacology

Enriched environment and acceleration of visual system development

https://doi.org/10.1016/j.neuropharm.2004.07.008Get rights and content

Abstract

Rearing mice from birth in an enriched environment leads to a conspicuous acceleration of visual system development appreciable at behavioral, electrophysiological and molecular level. Little is known about the possible mechanisms of action through which enriched environment affects visual system development. It has been suggested that differences in maternal behavior between enriched and non-enriched conditions could contribute to the earliest effects of enriched environment on visual development and that neurotrophins, BDNF in particular, might be involved. Here, we examined Brain Derived Neurotrophic Factor (BDNF) levels in the visual cortex during development and showed that an increase occurs in the first week of life in enriched pups compared to standard reared pups; BDNF levels at birth were equal in the two groups. This suggests a postnatal rather than a prenatal effect of environment on BDNF. A detailed analysis of maternal care behavior showed that pups raised in a condition of social and physical enrichment experienced higher levels of licking behavior and physical contact compared to standard reared pups and that enhanced levels of licking were also provided to pups in an enriched environment where no adult females other than the mother were present. Thus, different levels of maternal care in different environmental conditions could act as indirect mediator for the earliest effects of enrichment on visual system development.

Some of the effects of different levels of maternal care on the offspring behavior are long lasting. We measured the visual acuity of differentially reared mice at the end of the period of visual acuity development (postnatal day 45) and at 12 months of age, using a behavioral discrimination task. We found better learning abilities and higher visual acuity in enriched compared to standard reared mice at both ages.

Introduction

Environmental enrichment is a widely used paradigm for investigating the influence of sensory experience on brain and behavior. The enriched environment was first defined by Rosenzweig et al. (1978) as “a combination of complex inanimate and social stimulation”. “Enriched” animals are reared in larger cages and in larger groups and a variety of toys, tunnels, nesting material, stairs are present and changed frequently. In addition, animals are typically given the opportunity for voluntary physical activity on running wheels. Rearing animals in an enriched environment has profound effects on the adult organism, leading to anatomical changes (observed, for instance, in the cortex, hippocampus and cerebellum) in dendritic arborization, spine density and synapses per neuron (Rosenzweig, 1966, Greenough and Volkmar, 1973, Renner and Rosenzweig, 1987, Rampon et al., 2000). These morphological changes are associated with improved learning and memory and enhanced neural plasticity (reviewed in van Praag et al., 2000) and reorganization of cortical somatosensory maps (Polley et al., 2004).

Despite the large amount of data on adult animals, the possibility that an enhanced sensory-motor stimulation provided by an enriched environment early in life could also affect the development of the nervous system has been explored only very recently. More complex dendritic arbors were found in cortical pyramidal cells following enrichment from weaning (Kolb, 1995) but little else is known. Focusing on visual system development as a paradigmatic model of nervous system development, we showed that postweaning environmental enrichment prevents dark rearing effects on rat visual cortical development (Bartoletti et al., 2004), while environmental enrichment from birth in mice results in a conspicuous acceleration of visual system development at behavioral, electrophysiological and molecular level (Cancedda et al., 2004). Some of the main changes we found in enriched mice were observed at a very early age (postnatal days 7–15, (P7–P15)), when pups still spend all their time in the nest. The precociousness of these events makes unlikely that they derive from a direct influence of the richness of the environment on pups. Therefore, we hypothesized that different levels of maternal care in the two environmental conditions could act as an indirect mediator for the earliest effects of enrichment on visual system development (Cancedda et al., 2004). The hypothesis that different levels of maternal care in enriched condition could induce the precocious development of the visual system in enriched animals is also suggested by results showing that variations in maternal care can affect BDNF levels and neural development of the offspring (Liu et al., 1997). Neurotrophins, and in particular, BDNF, have a major role in the control of visual cortical plasticity during a critical period early in life (reviewed in Berardi et al., 2003).

To date, the relationship between enriched environment and maternal care in rodents has rarely been investigated: a similarity between the effects of environmental enrichment in the adult and early-life handling stimulation (short periods of maternal separation provided daily to pups) has been suggested (reviewed in Fernandez-Teruel et al., 2002), but a comparison of maternal behavior between enriched and standard dams is still missing. Here, we investigated maternal care influence on the acceleration of visual system development in environmentally enriched mice by analyzing maternal behavior in enriched and standard reared mice during the first 10 days of life. In addition, we measured BDNF expression in the visual cortex from P0 to P25 to understand whether maternal behavior influences this important determinant of visual cortical development.

Early work by Levine (1957) has shown that early stimulation of neonatal rodents affects their endocrine and behavioral responses later in life. In particular, numerous studies have clearly indicated that manipulations of the mother–infant relationship have long-term consequences on neuroendocrine and behavioral responses (reviewed in Cirulli et al., 2003a), and enhanced learning and memory have been reported in adult animals that received high levels of maternal care during development (Liu et al., 2000). One outstanding change induced by environmental enrichment from birth in mice is an improvement in the adult visual acuity, a result shown by Prusky et al. (2000a) and recently confirmed by us using behavioral as well as electrophysiological methods (Cancedda et al., 2004). To assess whether this augmented visual acuity induced by environmental enrichment also persists into old age and whether environmental enrichment has a protective role on the known visual loss associated with aging, we studied visual acuity in 12 months-old mice reared from birth in enriched or standard environment.

Section snippets

Subjects and mating protocol

The animals (C57BL/6J mice) were housed in a room with a temperature of 21 °C, 12/12 light/dark cycle, and food and water available ad libitum. To avoid possible confounding effects deriving from the experience of previous motherhood only primiparous females were employed. Female mice were assigned either to enriched or to standard cages and put with males (one male for every mating cage) in their respective cage, from which males were removed after 10 days. At least 7 days before delivery,

Results

We have recently demonstrated that rearing mice from birth in an enriched environment leads to a profound acceleration of important properties of visual system development (Cancedda et al., 2004). We found that raising mice in this condition causes a precocious maturation of visual acuity, measured both behaviorally and electrophysiologically. The mature visual acuity of EC and SC mice was also significantly different (Fig. 1(A)).

A profound visual system development acceleration was also found

Discussion

Neurotrophins have a major role in the control of visual cortical plasticity during a critical period early in life (reviewed in Berardi et al., 2003). In particular, BDNF exerts profound influence on the development of the visual system. BDNF overexpressing mice generated by Huang et al. (1999) exhibit a pronounced acceleration in both the development of visual acuity and the time course of ocular dominance and synaptic plasticity. We have recently demonstrated that changes very similar to

Acknowledgements

We thank Dr. E. Strettoi for her precious help in housing the animals and Mr. G. Cappagli and Mr. C. Orsini for their technical assistance. This research was supported by MIUR COFIN 2001 and 2002, CNR project SP-5, Progetto Strategico Neuroscienze CNR, FIRB project RBNE01RZH4-002.

References (60)

  • L.J. Marton et al.

    Molecular and cellular functions of the polyamines

  • A.K. McAllister et al.

    Neurotrophins regulate dendritic growth in developing visual cortex

    Neuron

    (1995)
  • A.K. McAllister et al.

    Neurotrophin regulation of cortical dendritic growth requires activity

    Neuron

    (1996)
  • J. Pauk et al.

    Positive effects of tactile versus kinesthetic or vestibular stimulation on neuroendocrine and ODC activity in maternally-deprived rat pups

    Life Sciences

    (1986)
  • T.M. Pham et al.

    Environmental influences on brain neurotrophins in rats

    Pharmacology, Biochemistry and Behavior

    (2002)
  • G.T. Prusky et al.

    Environmental enrichment from birth enhances visual acuity but not place learning in mice

    Behavioural Brain Research

    (2000)
  • G.T. Prusky et al.

    Behavioral assessment of visual acuity in mice and rats

    Vision Research

    (2000)
  • M.R. Rosenzweig et al.

    Social grouping cannot account for cerebral effects of enriched environments

    Brain Research

    (1978)
  • C. Sala et al.

    Regulation of dendritic spine morphology and synaptic function by Shank and Homer

    Neuron

    (2001)
  • J.L. Smart et al.

    Evidence of non-maternally mediated acceleration of eye-opening in ‘enriched’ artificially reared rat pups

    Brain Research. Developmental Brain Research

    (1990)
  • S.A. Barnett et al.

    Early stimulation and maternal behaviour

    Nature

    (1967)
  • A. Bartoletti et al.

    Environmental enrichment prevents effects of dark-rearing in the rat visual cortex

    Nature Neuroscience

    (2004)
  • M.F. Bear et al.

    Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist

    Journal of Neuroscience

    (1990)
  • L. Cancedda et al.

    Acceleration of visual system development by environmental enrichment

    Journal of Neuroscience

    (2004)
  • E. Carro et al.

    Circulating insulin-like growth factor I mediates effects of exercise on the brain

    Journal of Neuroscience

    (2000)
  • M. Fagiolini et al.

    Separable features of visual cortical plasticity revealed by N-methyl-d-aspartate receptor 2A signaling

    Proceedings of the National Academy of Sciences USA

    (2003)
  • K.M. Frick et al.

    Effects of environmental enrichment on spatial memory and neurochemistry in middle-aged mice

    Learning and Memory

    (2003)
  • L. Frolich et al.

    Brain insulin and insulin receptors in aging and sporadic Alzheimer’s disease

    Journal of Neural Transmission

    (1998)
  • J. Grutzendler et al.

    Long-term dendritic spine stability in the adult cortex

    Nature

    (2002)
  • M.A. Hofer

    Relationships as regulators: a psychobiologic perspective on bereavement

    Psychosomatic Medicine

    (1984)
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