A rich environmental experience reactivates visual cortex plasticity in aged rats

CNR Neuroscience Institute, via Moruzzi 1, I-56124, Pisa, Italy.
Experimental gerontology (Impact Factor: 3.49). 02/2012; 47(4):337-41. DOI: 10.1016/j.exger.2012.01.007
Source: PubMed


Brain aging is characterized by functional deterioration across multiple systems, associated to a progressive decay of neural plasticity. Here, we explored environmental enrichment (EE), a condition of enhanced sensory-motor and cognitive stimulation, as a strategy to restore plasticity processes in the old brain. Visual system is one of the paradigmatic models for studying experience-dependent plasticity. While reducing input from one eye through monocular deprivation induces a marked ocular dominance (OD) shift of neurons in the primary visual cortex during development, the same manipulation is totally ineffective after the closure of the critical period. We show that EE is able to reactivate OD plasticity in the visual cortex of aging rats, as assessed with both visual-evoked potentials and single-unit recordings. A marked reduction in intracortical GABAergic inhibition and a remodeling of extracellular matrix accompany this effect. The non-invasive nature of EE makes this paradigm eligible for human application.

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    • "Since shortterm DE reduced the number of PNNs compared to LR-controls, the reduced expression of PNNs most likely has contributed to the increased OD-plasticity after DE. A reduced PNN-density was recently also reported after short-term EE-housing in rat V1 which increased plasticity (Sale et al., 2007; Scali et al., 2012). Likewise, orthodenticle homeobox 2 homeoprotein binding to PNNs might regulate plasticity: a transient loss of Otx2 lead to a reduction of both PV + and PNN expression in adult mouse V1 and reopened plasticity of visual acuity after MD (Beurdeley et al., 2012). "
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    ABSTRACT: In the primary visual cortex (V1), monocular deprivation (MD) induces a shift in the ocular dominance (OD) of binocular neurons towards the open eye (Wiesel and Hubel, 1963; Gordon and Stryker, 1996). In V1 of C57Bl/6J mice, this OD-plasticity is maximal in juveniles, declines in adults and is absent beyond postnatal day (PD) 110 (Lehmann and Löwel, 2008) if mice are raised in standard cages. Since it was recently shown that brief dark exposure (DE) restored OD-plasticity in young adult rats (PD70-100) (He et al., 2006), we wondered whether DE would restore OD-plasticity also in adult and old mice and after a cortical stroke. To this end, we raised mice in standard cages until adulthood and transferred them to a darkroom for 10-14 days. Using intrinsic signal optical imaging we demonstrate that short-term DE can restore OD-plasticity after MD in both adult (PD138) and old mice (PD535), and that OD-shifts were mediated by an increase of open eye responses in V1. Interestingly, restored OD-plasticity after DE was accompanied by a reduction of both parvalbumin expressing cells and perineuronal nets and was prevented by increasing intracortical inhibition with diazepam. DE also maintained OD-plasticity in adult mice (PD150) after a stroke in the primary somatosensory cortex. In contrast, short-term DE did not affect basic visual parameters as measured by optomotry. In conclusion, short-term DE was able to restore OD-plasticity in both adult and aging mice and even preserved plasticity after a cortical stroke, most likely mediated by reducing intracortical inhibition.
    Experimental Gerontology 09/2014; 60. DOI:10.1016/j.exger.2014.09.007 · 3.49 Impact Factor
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    • "Sale et al. (2007) have also shown that EE exposure results in a decrease in basal extracellular GABA levels in the visual cortex, and that EE-induced plasticity can be countered by pharmacologically increasing inhibitory activity. EE-induced decreases in cortical inhibition have been demonstrated in studies of auditory and visual cortex, through decreases in GABA receptor subunit expression, inhibitory synapse density and basal levels of GABA (Beaulieu and Colonnier, 1987; Zhou et al., 2011; Jakkamsetti et al., 2012), while GAD67 expression has also been shown to decrease following exposure to EE (Scali et al., 2012; Tognini et al., 2012). However, decreased inhibition may just be one mechanism underlying EE-induced plasticity via shifts in the excitation/inhibition balance, with studies also suggesting an increase in cortical excitation with EE. "
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    ABSTRACT: The brain's life-long capacity for experience-dependent plasticity allows adaptation to new environments or to changes in the environment, and to changes in internal brain states such as occurs in brain damage. Since the initial discovery by Hebb (1947) that environmental enrichment (EE) was able to confer improvements in cognitive behavior, EE has been investigated as a powerful form of experience-dependent plasticity. Animal studies have shown that exposure to EE results in a number of molecular and morphological alterations, which are thought to underpin changes in neuronal function and ultimately, behavior. These consequences of EE make it ideally suited for investigation into its use as a potential therapy after neurological disorders, such as traumatic brain injury (TBI). In this review, we aim to first briefly discuss the effects of EE on behavior and neuronal function, followed by a review of the underlying molecular and structural changes that account for EE-dependent plasticity in the normal (uninjured) adult brain. We then extend this review to specifically address the role of EE in the treatment of experimental TBI, where we will discuss the demonstrated sensorimotor and cognitive benefits associated with exposure to EE, and their possible mechanisms. Finally, we will explore the use of EE-based rehabilitation in the treatment of human TBI patients, highlighting the remaining questions regarding the effects of EE.
    Frontiers in Systems Neuroscience 09/2014; 8. DOI:10.3389/fnsys.2014.00156
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    • "Induction of adult cortical plasticity appears then to be brought about primarily through a decrease in cortical inhibitory activity (Hensch and Fagiolini, 2005; Sale et al., 2007; Benali et al., 2008; Baroncelli et al., 2010, 2011; Luz and Shamir, 2012). Consistent with this idea, EE causes a reduction in the number of visual cortical neurons expressing GAD67 (Scali et al., 2012; Tognini et al., 2012), and a decrease in extracellular basal GABA levels, coupled with a restoration of white matter long-term potentiation (WM-LTP), suggesting decreased cortical inhibition (Sale et al., 2007). Decreases in GABAergic inhibition after EE, through a reduction in expression of GABAA receptor subunits, have been demonstrated in adult rat auditory cortex (Zhou et al., 2011), and in cat visual cortex enrichment decreases the number of inhibitory synapses (Beaulieu and Colonnier, 1987). "
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    ABSTRACT: Enriched social and physical housing produces many molecular, anatomical, electrophysiological and behavior benefits even in adult animals. Much less is known of its effects on cortical electrophysiology, especially in how sensory cortex encodes the altered environment, and extant studies have generally been restricted to neurons in input laminae in sensory cortex. To extend the understanding of how an enriched environment alters the way in which cortex views the world, we investigated enrichment-induced changes in neuronal encoding of sensory stimuli across all laminae of the rat barrel cortex receiving input from the face whisker tactile system. Animals were housed in Enriched (n = 13) or Isolated housing (n = 13) conditions for 8 weeks before extracellular recordings were obtained from barrel cortex in response to simple whisker deflections and whisker motions modeling movements seen in awake animals undertaking a variety of different tasks. Enrichment resulted in increases in neuronal responses to all stimuli, ranging from those modeling exploratory behavior through to discrimination behaviors. These increases were seen throughout the cortex from supragranular layers through to input Layer 4 and for some stimuli, in infragranular Layer 5. The observed enrichment-induced effect is consistent with the postulate that enrichment causes shift in cortical excitatory/inhibitory balance, and we demonstrate this is greatest in supragranular layers. However, we also report that the effects are non-selective for stimulus parameters across a range of stimuli except for one modeling the likely use of whiskers by the rats in the enriched housing.
    Frontiers in Cellular Neuroscience 08/2013; 7:124. DOI:10.3389/fncel.2013.00124 · 4.29 Impact Factor
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