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Recovery from amblyopia in adults via decreased visual cortical inhibition caused by experience in an enriched environment


The mammalian primary visual cortex (V1) became a prime model for the study of neural substrates underlying the development of cortical circuits. A series of pioneering experiments carried out by Hubel and Wiesel (1969, 1972) demonstrated the existence of ocular dominance (OD) columns in the cortex. Thalamic projections that target V1, as well as V1 's intrinsic connectivity, are arranged in alternating columns of neurons that are driven to different degrees by visual stimuli presented to either eye (Hubel and Wiesel 1969, 1972; Hubel et al 1977). Importantly, it was found that anomalous visual experience during a 'critical period' of post-natal development had a marked impact on the functional organization these OD columns: V1 neurons of animals that had been monocularly deprived underwent 'shifts' in OD; with time after sensory deprivation, the large majority of the V1 neuronal population would modify their responsiveness towards the non-deprived eye (Hubel et al 1977; Blakemore et al 1978). Subsequent studies provided clear evidence that the development of OD columns in V1, and their malleability within the critical period, depend both on innate and experiential factors (for review, see Katz and Crowley 2002). These findings shed significant light onto the mechanistic basis of numerous clinical conditions like amblyopia, which is characterized by poor performance, or acuity, of one or both eyes in the absence of physical abnormalities. Although amblyopia can be treated in children, the capacity for functional recovery significantly diminishes as a function of age; this condition is thought to be permanent in adults due to the decrease in visual cortical plasticity that follows the critical period. A remarkable report by Sale and colleagues (2007), published in Nature Neuroscience, highlights potential interventions that may rescue mal-adaptive plasticity in adults, as in the case of amblyopia, where changes in visual performance are detrimental. Furthermore, in this article the authors have discovered and described a central role for intra-cortical inhibition in the regulation of plasticity states in the visual cortex. Authors exposed adult rats to an enriched environment (EE), a protocol that provides subjects with greater variability in sensory and motor experiences relative to standard home cages, and known to drive robust anatomical and functional plasticity in most sensory cortices (for reviews, see van Praag et al 2000; Pinaud 2004). Enhanced visual experience in the EE recovered amblyopia induced by monocular deprivation followed by reverse-suture. The recovery of visual acuity was evidenced both by electrophysiological recordings of visual evoked potentials and by a standard visual acuity behavioural test (visual water-box task). Interestingly, this EE-induced recuperation of visual acuity paralleled a recovery in binocularity and appeared to be long-lasting, persisting for a minimum of two weeks. Thus, compared to controls housed in standard conditions, adult rats exposed to environmental enrichment display significant functional plasticity of V1 circuitry that impacts visual acuity behaviour. Sale and co-workers next investigated if the restoration of visual acuity by EE exposure was associated with alterations in inhibitory transmission. Intra-cortical inhibition had been shown previously to dynamically regulate receptive field (RF) properties such as area, direction and orientation selectivity and, importantly, plasticity associated with OD (Sillito 1977, 1979; Eysel et al 1998; Tremere and Pinaud 2005). Previous research has demonstrated that the maturation of the inhibitory network of the visual cortex correlates with the progression and closure of the critical period for plasticity of OD (Huang et al 1999; Tremere and Pinaud 2005). Using in vivo brain microdialysis, Sale and co-workers showed that exposure of adult amblyopic animals to the EE setting led to a 3-fold decrease in baseline GAB A levels in the bi......

【关 键 词】: amblyopia, gaba, ocular dominance, plasticity, visual
【期刊名称】: Journal of Biosciences
【期刊论文数据库】: [DBS_Articles_01]
【期刊论文编号】: 107,848,379
【摘要长度】: 4,000
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