Opinion
A Systematic Look at Environmental Modulation and Its Impact in Brain Development

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Trends

A large number of experimental procedures are being used to investigate the impact of the environment on brain plasticity, calling for a standardization of the available possibilities.

The most widely used interventions are aimed at either enhancing or reducing the intensity of stimuli, focusing either on specific sensory channels or acting in a multi-domain manner.

Combining different environmental manipulations together can result in new powerful settings aimed at investigating neural plasticity and the underlying molecular mechanisms.

The effects, positive or negative, elicited by one environmental manipulation can often be reversed by the successive application of a different procedure that has an effect in the opposite direction, offering windows for therapeutic applications.

The outcome of a given set of environmental modulations can be highly age-dependent.

Strong gene × environment interactions must be taken into account, with the impact of environmental procedures being influenced by the specific genetic background of the individual.

Several experimental procedures are currently used to investigate the impact of the environment on brain plasticity under physiological and pathological conditions. The available methodologies are aimed at obtaining global or specific reductions or intensifications of the stimuli, with initial standardization in animal models being paralleled by translational applications to humans. More procedures can be combined together or applied in series to obtain powerful experimental paradigms, and the choice of a given setting should take into account the specific genetic background, age, and phenotypic vulnerabilities of the target subjects. Sophisticated use of environmental manipulations can increase our knowledge of the mechanisms underlying experience-dependent plasticity, opening the way for new therapies for neurodevelopmental disorders, dysfunctions of plasticity, and brain aging.

Section snippets

Opening a Window to Brain Plasticity by Modulation of the Environment

Neural plasticity refers to the ability of the nervous system to reorganize its connections functionally and structurally in response to changes in environmental experience. Plasticity is particularly high during developmental time-windows termed critical periods (CPs, see Glossary) – defined phases of exceptional sensitivity to experience [1].

The potency of the environment in driving long-lasting neural and behavioral changes is highlighted by the effects elicited by experimental procedures

The Environment as a Tool: A Methodological Classification

In studying experience-dependent plasticity, the first step obviously consists of imposing controlled stimuli to selected individuals. This can be done directly, acting on the same individuals that are also used for monitoring the final effects on neural plasticity, or more indirectly, acting on intermediary individuals. A crucial point is the invasive nature of the procedure adopted to modulate specific stimuli, together with the time-window in which the manipulations are performed. In the

In Search of a ‘Standard’ Environment

The definitions of the manipulations described so far are based on the assumption that some specific changes are applied, for reaching particular aims, starting from a normative reference condition that is generally referred to as ‘standard laboratory conditions’ (SCs). In SCs the animals are reared in small social groups and in very simple cages where only nesting material, food, and water are present, without the opportunity for enhanced stimulation or the risk of encountering harmful

Concluding Remarks

The environment is a double-edged sword. Impoverishing stimuli, reduced social interactions, and engaging in repetitive activities are key examples of potentially harmful environmental conditions that can depress cerebral functions, induce abnormal developmental processes, and predispose individuals to pathological aging and dementia. On the other hand, enhanced social care, optimized cognitive stimulation, and physical exercise are all opportunities for empowering brain plasticity (Figure 2).

Acknowledgments

This work was supported by European Research Area (ERA)-NET NEURON grant NeuroDREAM and by a Progetti di Ricerca di Interesse Nazionale (PRIN)-Ministero dell’Istruzione dell’Università e della Ricerca (MIUR) 2015 grant to A.S.

Glossary

Brain-derived neurotrophic factor (BDNF)
a member of the neurotrophin family of growth factors. It is strongly involved in neurogenesis, neuronal survival and differentiation, and in the regulation of synaptic transmission, brain plasticity, learning processes, and memory functions.
Critical period (CP)
a temporally defined phase of enhanced sensitivity of neuronal circuitries to changes in environmental stimuli. There are CPs for several different functions such as the acquisition of language,

References (76)

  • I. Branchi

    Shaping brain development: mouse communal nesting blunts adult neuroendocrine and behavioral response to social stress and modifies chronic antidepressant treatment outcome

    Psychoneuroendocrinology

    (2010)
  • C.R. Pryce et al.

    Chronic psychosocial stressors in adulthood: studies in mice, rats and tree shrews

    Neurobiol. Stress

    (2017)
  • L. Baroncelli

    Enriched experience and recovery from amblyopia in adult rats: impact of motor, social and sensory components

    Neuropharmacology

    (2012)
  • A. Sale

    Enrich the environment to empower the brain

    Trends Neurosci.

    (2009)
  • T. Begenisic

    Early environmental therapy rescues brain development in a mouse model of Down syndrome

    Neurobiol. Dis.

    (2015)
  • M.K. Erschbamer

    Neither environmental enrichment nor voluntary wheel running enhances recovery from incomplete spinal cord injury in rats

    Exp. Neurol.

    (2006)
  • F. Cirulli

    A novel BDNF polymorphism affects plasma protein levels in interaction with early adversity in rhesus macaques

    Psychoneuroendocrinology

    (2011)
  • C. Martinez-Cue

    Behavioral, cognitive and biochemical responses to different environmental conditions in male Ts65Dn mice, a model of Down syndrome

    Behav. Brain Res.

    (2005)
  • B.S. Wang

    Environmental enrichment rescues binocular matching of orientation preference in mice that have a precocious critical period

    Neuron

    (2013)
  • G. Lonetti

    Early environmental enrichment moderates the behavioral and synaptic phenotype of MeCP2 null mice

    Biol. Psychiatry

    (2010)
  • Y. Pena

    Enduring effects of environmental enrichment from weaning to adulthood on pituitary–adrenal function, pre-pulse inhibition and learning in male and female rats

    Psychoneuroendocrinology

    (2009)
  • T. Baraldi

    Cognitive stimulation during lifetime and in the aged phase improved spatial memory, and altered neuroplasticity and cholinergic markers of mice

    Exp. Gerontol.

    (2013)
  • K. Mahati

    Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity

    Neurobiol. Learn. Mem.

    (2016)
  • R. Cai

    Environmental enrichment improves behavioral performance and auditory spatial representation of primary auditory cortical neurons in rat

    Neurobiol. Learn. Mem.

    (2009)
  • C. Lunghi et al.

    A cycling lane for brain rewiring

    Curr. Biol.

    (2015)
  • T.Y. Zhang

    Epigenetic mechanisms for the early environmental regulation of hippocampal glucocorticoid receptor gene expression in rodents and humans

    Neuropsychopharmacology

    (2013)
  • E. Putignano

    Developmental downregulation of histone posttranslational modifications regulates visual cortical plasticity

    Neuron

    (2007)
  • G. Purpura

    Effect of early multisensory massage intervention on visual functions in infants with Down syndrome

    Early Hum. Dev.

    (2014)
  • T. Ngandu

    A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial

    Lancet

    (2015)
  • A. Sale

    Environment and brain plasticity: towards an endogenous pharmacotherapy

    Physiol. Rev.

    (2014)
  • D. Liu

    Maternal care, hippocampal glucocorticoid receptors, and hypothalamic–pituitary–adrenal responses to stress

    Science

    (1997)
  • C. Raineki

    Neonatal handling: an overview of the positive and negative effects

    Dev. Psychobiol.

    (2014)
  • C.A. Nelson

    The neurobiological toll of early human deprivation

    Monogr. Soc. Res. Child Dev.

    (2011)
  • R. Perry et al.

    Neurobiology of attachment to an abusive caregiver: short-term benefits and long-term costs

    Dev. Psychobiol.

    (2014)
  • E.J. McCrory

    Annual research review: childhood maltreatment, latent vulnerability and the shift to preventative psychiatry – the contribution of functional brain imaging

    J. Child Psychol. Psychiatry

    (2017)
  • S. Spinelli

    Early-life stress induces long-term morphologic changes in primate brain

    Arch. Gen. Psychiatry

    (2009)
  • G. Conti

    Primate evidence on the late health effects of early-life adversity

    Proc. Natl. Acad. Sci. U. S. A.

    (2012)
  • M. Rosenzweig

    Modification of brain circuits through experience

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