A rich environmental experience reactivates visual cortex plasticity in aged rats.
ABSTRACT 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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ABSTRACT: Amblyopia is a neurodevelopmental disorder of vision caused by abnormal visual experience during early childhood that is often considered to be untreatable in adulthood. Recently, it has been shown that a novel dichoptic videogame-based treatment for amblyopia can improve visual function in adult patients, at least in part, by reducing inhibition of inputs from the amblyopic eye to the visual cortex. Non-invasive anodal transcranial direct current stimulation has been shown to reduce the activity of inhibitory cortical interneurons when applied to the primary motor or visual cortex. In this double-blind, sham-controlled cross-over study we tested the hypothesis that anodal transcranial direct current stimulation of the visual cortex would enhance the therapeutic effects of dichoptic videogame-based treatment. A homogeneous group of 16 young adults (mean age 22.1 ± 1.1 years) with amblyopia were studied to compare the effect of dichoptic treatment alone and dichoptic treatment combined with visual cortex direct current stimulation on measures of binocular (stereopsis) and monocular (visual acuity) visual function. The combined treatment led to greater improvements in stereoacuity than dichoptic treatment alone, indicating that direct current stimulation of the visual cortex boosts the efficacy of dichoptic videogame-based treatment. This intervention warrants further evaluation as a novel therapeutic approach for adults with amblyopia.Journal of the American Society for Experimental NeuroTherapeutics 07/2013; · 5.38 Impact Factor
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ABSTRACT: Ocular dominance (OD) plasticity in mouse primary visual cortex (V1) declines during postnatal development and is absent beyond postnatal day 110 if mice are raised in standard cages (SCs). An enriched environment (EE) promotes OD plasticity in adult rats. Here, we explored cellular mechanisms of EE in mouse V1 and the therapeutic potential of EE to prevent impairments of plasticity after a cortical stroke. Using in vivo optical imaging, we observed that monocular deprivation in adult EE mice (i) caused a very strong OD plasticity previously only observed in 4-wk-old animals, (ii) restored already lost OD plasticity in adult SC-raised mice, and (iii) preserved OD plasticity after a stroke in the primary somatosensory cortex. Using patch-clamp electrophysiology in vitro, we also show that (iv) local inhibition was significantly reduced in V1 slices of adult EE mice and (v) the GABA/AMPA ratio was like that in 4-wk-old SC-raised animals. These observations were corroborated by in vivo analyses showing that diazepam treatment significantly reduced the OD shift of EE mice after monocular deprivation. Taken together, EE extended the sensitive phase for OD plasticity into late adulthood, rejuvenated V1 after 4 mo of SC-rearing, and protected adult mice from stroke-induced impairments of cortical plasticity. The EE effect was mediated most likely by preserving low juvenile levels of inhibition into adulthood, which potentially promoted adaptive changes in cortical circuits.Proceedings of the National Academy of Sciences 01/2014; · 9.81 Impact Factor
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ABSTRACT: Experience shapes neural circuits during critical periods in early life. The timing of critical periods is regulated by both genetics and the environment. Here we study the functional significance of such temporal regulations in the mouse primary visual cortex, where critical period plasticity drives binocular matching of orientation preference. We find that the binocular matching is permanently disrupted in mice that have a precocious critical period due to genetically enhanced inhibition. The disruption is specific to one type of neuron, the complex cells, which, as we reveal, normally match after the simple cells. Early environmental enrichment completely rescues the deficit by inducing histone acetylation and consequently advancing the matching process to coincide with the precocious plasticity. Our experiments thus demonstrate that the proper timing of the critical period is essential for establishing normal binocularity and the detrimental impact of its genetic misregulation can be ameliorated by environmental manipulations via epigenetic mechanisms.Neuron 09/2013; · 15.77 Impact Factor