In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.

No abstract

Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain-derived neurotrophic factor (BDNF+/-) and mice lacking neurotrophin-4 (NT-4-/-) together with their wild-type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild-type and enriched NT-4-/- mice showed a two-fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU-positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF+/- mice. Failure to up-regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT-4 is required for the environmental induction of neurogenesis.

Several examples of 'perceptual learning' (improvement of some perceptual task with practice) have been reported. These studies are of great interest for neurological research because they demonstrate plasticity of the nervous system. Even for apparently basic perceptual tasks, such as visual acuity or vernier acuity, practice can facilitate a neural change which enhances performance. One question in this field is where does this learning occur? Indications about the possible neural site of a learning process may be derived from its specificity for some particular stimulus parameters. For instance, there is a hint that learning in global stereopsis may occur at a stage where visual information is processed by mechanisms selectively sensitive to different stimulus orientations. We report here an experiment on perceptual learning in the discrimination of gratings of different waveform. Our findings show that learning is specific for both the orientation and the spatial frequency of the practice stimulus.

Visual deficits caused by abnormal visual experience during development are hard to recover in adult animals. Removal of chondroitin sulfate proteoglycans from the mature extracellular matrix with chondroitinase ABC promotes plasticity in the adult visual cortex. We tested whether chondroitinase ABC treatment of adult rats facilitates anatomical, functional, and behavioral recovery from the effects of a period of monocular deprivation initiated during the critical period for monocular deprivation. We found that chondroitinase ABC treatment coupled with reverse lid-suturing causes a complete recovery of ocular dominance, visual acuity, and dendritic spine density in adult rats. Thus, manipulations of the extracellular matrix can be used to promote functional recovery in the adult cortex.amblyopia ͉ chondroitin sulfate ͉ extracellular matrix ͉ glycosaminoglycan ͉ plasticity A n abnormal visual experience during development results in defective visual function. For instance, cataract or anisometropia in early childhood leads to a condition of reduced visual acuity (amblyopia) that can be fully recovered only if the treatment of these conditions is performed during early infancy (1). The lack of substantial recovery from amblyopia in the adult has been attributed to a decline in the plasticity of cortical circuits occurring during late postnatal development. Indeed, studies in animals have shown that monocular deprivation (MD) impairs visual cortical responses to the deprived eye and affects axonal morphology and dendritic spine density only if performed during a critical period of postnatal development (2-6). The ability to recover from the deficits induced by MD declines with age; reopening the previously deprived eye or reverse lidsuturing (RS) in young animals results in full recovery of ocular dominance, but these procedures become progressively less effective with age and are practically ineffective in the adult (7-9). Recovery from the amblyopic effect of MD is also progressively less efficient during development. In the adult, visual acuity shows small recoveries even if its final level continues to be pathologically low (10, 11). Similarly, a limited recovery of visual acuity can also be observed in adult amblyopic patients in particular conditions (1), although visual acuity remains largely abnormal.These observations suggest that the adult visual cortex expresses factors that inhibit experience-dependent plasticity and that develop in conjunction with the end of the critical period. The molecular identity of these factors is only partially known (12); studies performed in rodents have attributed the closure of the critical period to the maturation of inhibitory intracortical circuitry (13,14) and to developmental changes in the expression of molecular factors regulating synaptic plasticity (15, 16). Recently, it has been shown that at least part of the low level of plasticity of the adult visual cortex is due to the condensation of extracellular matrix molecules in perineuronal nets (PNNs). Indeed, chondr...

Brain aging is characterized by global changes which are thought to underlie age-related cognitive decline. These include variations in brain activity and the progressive increase in the concentration of soluble amyloid-β (Aβ) oligomers, directly impairing synaptic function and plasticity even in the absence of any neurodegenerative disorder. Considering the high social impact of the decline in brain performance associated to aging, there is an urgent need to better understand how it can be prevented or contrasted. Lifestyle components, such as social interaction, motor exercise and cognitive activity, are thought to modulate brain physiology and its susceptibility to age-related pathologies. However, the precise functional and molecular factors that respond to environmental stimuli and might mediate their protective action again pathological aging still need to be clearly identified. To address this issue, we exploited environmental enrichment (EE), a reliable model for studying the effect of experience on the brain based on the enhancement of cognitive, social and motor experience, in aged wild-type mice. We analyzed the functional consequences of EE on aged brain physiology by performing in vivo local field potential (LFP) recordings with chronic implants. In addition, we also investigated changes induced by EE on molecular markers of neural plasticity and on the levels of soluble Aβ oligomers. We report that EE induced profound changes in the activity of the primary visual and auditory cortices and in their functional interaction. At the molecular level, EE enhanced plasticity by an upward shift of the cortical excitation/inhibition balance. In addition, EE reduced brain Aβ oligomers and increased synthesis of the Aβ-degrading enzyme neprilysin. Our findings strengthen the potential of EE procedures as a non-invasive paradigm for counteracting brain aging processes.

No abstract

Brain plasticity refers to the remarkable property of cerebral neurons to change their structure and function in response to experience, a fundamental theoretical theme in the field of basic research and a major focus for neural rehabilitation following brain disease. While much of the early work on this topic was based on deprivation approaches relying on sensory experience reduction procedures, major advances have been recently obtained using the conceptually opposite paradigm of environmental enrichment, whereby an enhanced stimulation is provided at multiple cognitive, sensory, social, and motor levels. In this survey, we aim to review past and recent work concerning the influence exerted by the environment on brain plasticity processes, with special emphasis on the underlying cellular and molecular mechanisms and starting from experimental work on animal models to move to highly relevant work performed in humans. We will initiate introducing the concept of brain plasticity and describing classic paradigmatic examples to illustrate how changes at the level of neuronal properties can ultimately affect and direct key perceptual and behavioral outputs. Then, we describe the remarkable effects elicited by early stressful conditions, maternal care, and preweaning enrichment on central nervous system development, with a separate section focusing on neurodevelopmental disorders. A specific section is dedicated to the striking ability of environmental enrichment and physical exercise to empower adult brain plasticity. Finally, we analyze in the last section the ever-increasing available knowledge on the effects elicited by enriched living conditions on physiological and pathological aging brain processes.