Removing Brakes on Adult Brain Plasticity: From Molecular to Behavioral Interventions

Department of Brain and Cognitive Sciences, University of Rochester, Rochester New York 14627-0268, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 11/2010; 30(45):14964-71. DOI: 10.1523/JNEUROSCI.4812-10.2010
Source: PubMed


Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these "brakes" are structural, such as perineuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects.

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    • "If the lack of recovery from amblyopia in adult subjects is due to the low levels of plasticity of adult V1, enhancing V1 plasticity might allow the deprived eye input to regain access to visual cortical neurons, promoting recovery from amblyopia. Following this hypothesis, a new era of exciting experimental studies has recently started, leading to the demonstration and now widely accepted notion that a high degree of residual cortical plasticity can be unmasked in the adult brain (see, for instance, the review by Bavelier et al., 2010). "
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    ABSTRACT: Amblyopia is the most diffused form of visual function impairment affecting one eye, with a prevalence of 1–5% in the total world population. Amblyopia is usually caused by an early functional imbalance between the two eyes, deriving from anisometropia, strabismus, or congenital cataract, leading to severe deficits in visual acuity, contrast sensitivity and stereopsis. While amblyopia can be efficiently treated in children, it becomes irreversible in adults, as a result of a dramatic decline in visual cortex plasticity which occurs at the end of the critical period (CP) in the primary visual cortex. Notwithstanding this widely accepted dogma, recent evidence in animal models and in human patients have started to challenge this view, revealing a previously unsuspected possibility to enhance plasticity in the adult visual system and to achieve substantial visual function recovery. Among the new proposed intervention strategies, non invasive procedures based on environmental enrichment, physical exercise or visual perceptual learning (vPL) appear particularly promising in terms of future applicability in the clinical setting. In this survey, we will review recent literature concerning the application of these behavioral intervention strategies to the treatment of amblyopia, with a focus on possible underlying molecular and cellular mechanisms.
    Frontiers in Behavioral Neuroscience 10/2015; 9. DOI:10.3389/fnbeh.2015.00281 · 3.27 Impact Factor
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    • "Later several studies found evidence for experience-dependent neurogenesis in the hippocampi of adult mice (for a review see [2]). Today there is accumulating evidence that also the human brain continues to be shaped by experience throughout adulthood [3] [4] [5]. These adaptive changes have been shown to take place on structural as well as functional level [6] [7] [8] [9]. "
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    ABSTRACT: This study investigated the impact of “life kinetik” training on brain plasticity in terms of an increased functional connectivity during resting-state functional magnetic resonance imaging (rs-fMRI). The training is an integrated multimodal training that combines motor and cognitive aspects and challenges the brain by introducing new and unfamiliar coordinative tasks. Twentyone subjects completed at least 11 one-hour-per-week “life kinetik” training sessions in 13 weeks as well as before and after rsfMRI scans. Additionally, 11 control subjects with 2 rs-fMRI scans were included. The CONN toolbox was used to conduct several seed-to-voxel analyses. We searched for functional connectivity increases between brain regions expected to be involved in the exercises. Connections to brain regions representing parts of the defaultmode network, such asmedial frontal cortex and posterior cingulate cortex, did not change. Significant connectivity alterations occurred between the visual cortex and parts of the superior parietal area (BA7). Premotor area and cingulate gyrus were also affected.We can conclude that the constant challenge of unfamiliar combinations of coordination tasks, combined with visual perception and working memory demands, seems to induce brain plasticity expressed in enhanced connectivity strength of brain regions due to coactivation.
    Neural Plasticity 10/2015; · 3.60 Impact Factor
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    • "etworks and more extensive hard wiring of existing circuits ( Hensch , 2005 ) . Most importantly , invasive or noninvasive ( e . g . , pharmacological ) interventions resulting in decreased strength of certain inhibitory inputs were recently successfully used to enhance experience dependent neuronal plasticity in adult nervous system ( reviewed in Bavelier et al . , 2010 ) . Changes in inhibition were proposed to be particularly important for neuronal plasticity following sensory experience . It has been show that in the adult primary auditory cortex , the dynamics of synaptic receptive field plasticity is associated with a reduction of synaptic inhibition which was followed by a large increase in excit"
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    ABSTRACT: Learning and memory require alteration in number and strength of existing synaptic connections. Extracellular proteolysis within the synapses has been shown to play a pivotal role in synaptic plasticity by determining synapse structure, function, and number. Although synaptic plasticity of excitatory synapses is generally acknowledged to play a crucial role in formation of memory traces, some components of neural plasticity are reflected by nonsynaptic changes. Since information in neural networks is ultimately conveyed with action potentials, scaling of neuronal excitability could significantly enhance or dampen the outcome of dendritic integration, boost neuronal information storage capacity and ultimately learning. However, the underlying mechanism is poorly understood. With this regard, several lines of evidence and our most recent study support a view that activity of extracellular proteases might affect information processing in neuronal networks by affecting targets beyond synapses. Here, we review the most recent studies addressing the impact of extracellular proteolysis on plasticity of neuronal excitability and discuss how enzymatic activity may alter input-output/transfer function of neurons, supporting cognitive processes. Interestingly, extracellular proteolysis may alter intrinsic neuronal excitability and excitation/inhibition balance both rapidly (time of minutes to hours) and in long-term window. Moreover, it appears that by cleavage of extracellular matrix (ECM) constituents, proteases may modulate function of ion channels or alter inhibitory drive and hence facilitate active participation of dendrites and axon initial segments (AISs) in adjusting neuronal input/output function. Altogether, a picture emerges whereby both rapid and long-term extracellular proteolysis may influence some aspects of information processing in neurons, such as initiation of action potential, spike frequency adaptation, properties of action potential and dendritic backpropagation.
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