Experience-dependent changes in NMDAR1 expression in the visual 
cortex of an animal model for amblyopia

When normal binocular visual experience is disrupted during postnatal development, it affects the maturation of cortical circuits and often results in the development of poor visual acuity known as amblyopia. Two main factors contribute to the development of amblyopia: visual deprivation and reduced binocular competition. We investigated the affect of these two amblyogenic factors on the expression of the NMDAR1 subunit in the visual cortex because activation of the NMDA receptor is a key mechanism of developmental neural plasticity. We found that disruption of binocular correlations by monocular deprivation promoted a topographic loss of NMDAR1 expression within the cortical representations of the central visual field and the vertical and horizontal meridians. In contrast, binocular deprivation, which primarily affects visual deprivation, promoted an increase in NMDAR1 expression throughout the visual cortex. These different changes in NMDAR1 expression can be described as topographic and homeostatic plasticity of NMDA expression, respectively. In addition, the changes in NMDA expression in the visual cortex provide a greater understanding of the neural mechanisms that underlie the development of amblyopia and the potential for visual recovery.

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IGF-1 Restores Visual Cortex Plasticity in Adult Life by Reducing Local GABA Levels

Neural Plasticity ◽

10.1155/2012/250421 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 22

Author(s):

José Fernando Maya-Vetencourt ◽

Laura Baroncelli ◽

Alessandro Viegi ◽

Ettore Tiraboschi ◽

Eero Castren ◽

...

Keyword(s):

Nervous System ◽

Visual Cortex ◽

Neural Plasticity ◽

Cortical Neurons ◽

Environmental Enrichment ◽

Adult Life ◽

Monocular Deprivation ◽

Adult Brain ◽

Environmental Stimulation ◽

The Central Nervous System

The central nervous system architecture is markedly modified by sensory experience during early life, but a decline of plasticity occurs with age. Recent studies have challenged this dogma providing evidence that both pharmacological treatments and paradigms based on the manipulation of environmental stimulation levels can be successfully employed as strategies for enhancing plasticity in the adult nervous system. Insulin-like growth factor 1 (IGF-1) is a peptide implicated in prenatal and postnatal phases of brain development such as neurogenesis, neuronal differentiation, synaptogenesis, and experience-dependent plasticity. Here, using the visual system as a paradigmatic model, we report that IGF-1 reactivates neural plasticity in the adult brain. Exogenous administration of IGF-1 in the adult visual cortex, indeed, restores the susceptibility of cortical neurons to monocular deprivation and promotes the recovery of normal visual functions in adult amblyopic animals. These effects were accompanied by a marked reduction of intracortical GABA levels. Moreover, we show that a transitory increase of IGF-1 expression is associated to the plasticity reinstatement induced by environmental enrichment (EE) and that blocking IGF-1 action by means of the IGF-1 receptor antagonist JB1 prevents EE effects on plasticity processes.

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Binocular competition affects the pattern and intensity of ocular activation columns in the visual cortex of cats

Visual Neuroscience ◽

10.1017/s0952523800002200 ◽

1989 ◽

Vol 2 (4) ◽

pp. 391-407 ◽

Cited By ~ 12

Author(s):

N. Tumosa ◽

S. B. Tieman ◽

D. G. Tieman

Keyword(s):

Visual Cortex ◽

Competitive Advantage ◽

Monocular Deprivation ◽

Area 17 ◽

Large Area ◽

Cortical Cells ◽

Areas 17 And 18 ◽

Binocular Competition ◽

Video Densitometry ◽

Average Size

AbstractThe effect of binocular competition on the development of ocular activation columns in areas 17 and 18 of cats was studied using the 14C-2-deoxyglucose (14C-2DG) technique to visualize the regions of cortex activated by one eye in cats reared with equal alternating monocular exposure (equal AME), unequal AME, or monocular deprivation (MD). The average size of the ocular activation columns of the eye stimulated during administration of 2DG was positively correlated with the competitive advantage during rearing. In order of increasing percentage of visual cortex activated, the eyes were (1) deprived eye of MD cats, (2) less experienced eye of unequal AME cats, (3) either eye of equal AME cats, (4) more experienced eye of unequal AME cats, and (5) experienced eye of MD cats. In area 17, the shape of the activation columns also was affected by the relative experience of the eye. The columns of the deprived eye of MD cats were widest in layer IV, where they were about the same width as those of the less experienced eye of the unequal AME cats; in other layers they were narrower, sometimes disappearing altogether. In contrast, the activation columns of the less experienced eye of the unequal AME cats were about the same width in all layers. These results suggest that when one eye is placed at a severe disadvantage and receives no patterned input, as in MD, both geniculocortical connections and intracortical connections may be disrupted, but when the disadvantage is less, as in unequal AME, only the geniculocortical connections are disrupted.Binocular competition also affected the intensity of activation within columns in area 17. We used video densitometry to determine ratios of the amount of label in cortical and thalamic structures. Both the ratio of label in area 17 to that in the lateral geniculate nucleus (LGN) and the ratio of label in the binocular segment of area 17 to that in the monocular segment were significantly less for the deprived eye of MD cats than for any other group. These results suggest that even within the smaller activation columns, deprived geniculocortical afferents are relatively ineffective at driving cortical cells. This finding is consistent with earlier reports that the synapses from the deprived pathway are both morphologically abnormal and reduced in number. The cortical labeling for the less experienced eye of the unequal AME cats and the experienced eye of the MD cats were also significantly less than that in equal AME cats. The decreased labeling for the experienced eye activation columns suggests that, in order to cover an abnormally large area, afferents representing the experienced eye must make fewer synaptic contacts within that area and that there are intrinsic limits on the number of synapses that one axon can make.

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Short-term plasticity of the human adult visual cortex measured with 7T BOLD

10.1101/323741 ◽

2018 ◽

Cited By ~ 1

Author(s):

Paola Binda ◽

Jan W. Kurzawski ◽

Claudia Lunghi ◽

Laura Biagi ◽

Michela Tosetti ◽

...

Keyword(s):

Visual Cortex ◽

Frequency Tuning ◽

Ocular Dominance ◽

Monocular Deprivation ◽

Homeostatic Plasticity ◽

Short Term ◽

Parvocellular Pathway ◽

Human Adult ◽

Spatial Frequencies ◽

Ventral Pathway

AbstractVisual cortex, particularly V1, is considered to be resilient to plastic changes in adults. In particular, ocular dominance is assumed to be hard-wired after the end of the critical period. We show that short-term (2h) monocular deprivation in adult humans boosts the BOLD response to the deprived eye, changing ocular dominance of V1 vertices, consistently with homeostatic plasticity. The boost is strongest in V1, present in V2, V3 & V4 but absent in V3a and MT. Assessment of spatial frequency tuning in V1 by a population Receptive-Field technique shows that deprivation primarily boosts high spatial frequencies, consistent with a primary involvement of the parvocellular pathway. Crucially, the V1 deprivation effect correlates across participants with the perceptual increase of the deprived eye dominance assessed with binocular rivalry, suggesting a common origin. Our results demonstrate that visual cortex, particularly the ventral pathway, retains a high potential for homeostatic plasticity in the human adult.

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Early cross-modal interactions and adult human visual cortical plasticity revealed by binocular rivalry

10.36253/978-88-6655-687-9 ◽

2015 ◽

Author(s):

Claudia Lunghi

Keyword(s):

Visual Cortex ◽

Binocular Rivalry ◽

Visual Processing ◽

Cortical Plasticity ◽

Monocular Deprivation ◽

Homeostatic Plasticity ◽

Multisensory Perception ◽

Modal Interactions ◽

Early Visual Cortex ◽

Visual Cortical

In this research binocular rivalry is used as a tool to investigate different aspects of visual and multisensory perception. Several experiments presented here demonstrated that touch specifically interacts with vision during binocular rivalry and that the interaction likely occurs at early stages of visual processing, probably V1 or V2. Another line of research also presented here demonstrated that human adult visual cortex retains an unexpected high degree of experience-dependent plasticity by showing that a brief period of monocular deprivation produced important perceptual consequences on the dynamics of binocular rivalry, reflecting a homeostatic plasticity. In summary, this work shows that binocular rivalry is a powerful tool to investigate different aspects of visual perception and can be used to reveal unexpected properties of early visual cortex.

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Developmental Regulation of Homeostatic Plasticity in Mouse Primary Visual Cortex

10.1101/2021.06.11.448148 ◽

2021 ◽

Author(s):

Wei Wen ◽

Gina Turrigiano

Keyword(s):

Visual Cortex ◽

Primary Visual Cortex ◽

Pyramidal Neurons ◽

Neural Circuit ◽

Developmental Regulation ◽

Visual Deprivation ◽

Homeostatic Plasticity ◽

Designer Drugs ◽

Inhibitory Input ◽

Synaptic Scaling

Homeostatic plasticity maintains network stability by adjusting excitation, inhibition, or the intrinsic excitability of neurons, but the developmental regulation and coordination of these distinct forms of homeostatic plasticity remains poorly understood. A major contributor to this information gap is the lack of a uniform paradigm for chronically manipulating activity at different developmental stages. To overcome this limitation, we utilized Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to directly suppress neuronal activity in layer (L) 2/3 of mouse primary visual cortex (V1) at two important developmental timepoints: the classic visual system critical period (CP, P24-29), and adulthood (P45-55). We show that 24 hours of DREADD-mediated activity suppression simultaneously induces excitatory synaptic scaling up and intrinsic homeostatic plasticity in L2/3 pyramidal neurons during the CP, consistent with previous observations using prolonged visual deprivation. Importantly, manipulations known to block these forms of homeostatic plasticity when induced pharmacologically or via visual deprivation also prevented DREADD-induced homeostatic plasticity. We next used the same paradigm to suppress activity in adult animals. Surprisingly, while excitatory synaptic scaling persisted into adulthood, intrinsic homeostatic plasticity was completely absent. Finally, we found that homeostatic changes in quantal inhibitory input onto L2/3 pyramidal neurons were absent during the CP but present in adults. Thus, the same population of neurons can express distinct sets of homeostatic plasticity mechanisms at different development stages. Our findings suggest that homeostatic forms of plasticity can be recruited in a modular manner according to the evolving needs of a developing neural circuit.

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Arc restores juvenile plasticity in adult mouse visual cortex

10.1101/130880 ◽

2017 ◽

Author(s):

Kyle R. Jenks ◽

Taekeun Kim ◽

Elissa D. Pastuzyn ◽

Hiroyuki Okuno ◽

Andrew V. Taibi ◽

...

Keyword(s):

Visual Cortex ◽

Neural Plasticity ◽

Critical Period ◽

Adult Mouse ◽

Monocular Deprivation ◽

Protein Synthesis Inhibitor ◽

Adult Mice ◽

Mouse Visual Cortex ◽

Activity Dependent

AbstractThe molecular basis for the decline in experience-dependent neural plasticity over age remains poorly understood. In visual cortex, the robust plasticity induced in juvenile mice by brief monocular deprivation (MD) during the critical period is abrogated by genetic deletion of Arc, an activity-dependent regulator of excitatory synaptic modification. Here we report that augmenting Arc expression in adult mice prolongs juvenile-like plasticity in visual cortex, as assessed by recordings of ocular dominance (OD) plasticity in vivo. A distinguishing characteristic of juvenile OD plasticity is the weakening of deprived-eye responses, believed to be accounted for by the mechanisms of homosynaptic long-term depression (LTD). Accordingly, we also found increased LTD in visual cortex of adult mice with augmented Arc expression, and impaired LTD in visual cortex of juvenile mice that lack Arc or have been treated in vivo with a protein synthesis inhibitor. Further, we found that although activity-dependent expression of Arc mRNA does not change with age, expression of Arc protein is maximal during the critical period and declines in adulthood. Finally, we show that acute augmentation of Arc expression in wild type adult mouse visual cortex is sufficient to restore juvenile-like plasticity. Together, our findings suggest a unifying molecular explanation for the age- and activity-dependent modulation of synaptic sensitivity to deprivation.Significance StatementNeuronal plasticity peaks early in life during critical periods and normally declines with age, but the molecular changes that underlie this decline are not fully understood. Using the mouse visual cortex as a model, we found that activity-dependent expression of the neuronal protein Arc peaks early in life, and that loss of activity-dependent Arc expression parallels loss of synaptic plasticity in the visual cortex. Genetic overexpression of Arc prolongs the critical period of visual cortex plasticity and acute viral expression of Arc in adult mice can restore juvenile-like plasticity. These findings provide a mechanism for the loss of excitatory plasticity with age, and suggest that Arc may be an exciting therapeutic target for modulation of the malleability of neuronal circuits.

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Classification of visual cortex plasticity phenotypes following treatment for amblyopia

10.1101/554576 ◽

2019 ◽

Author(s):

Justin L. Balsor ◽

David G. Jones ◽

Kathryn M. Murphy

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Monocular Deprivation ◽

Data Driven ◽

Adaptive Plasticity ◽

Gabaergic Receptors ◽

Data Driven Approach ◽

Binocular Deprivation ◽

Induced Changes

AbstractMonocular deprivation (MD) during the critical period (CP) has enduring effects on visual acuity and the functioning of the visual cortex (V1). This experience-dependent plasticity has become a model for studying the mechanisms, especially glutamatergic and GABAergic receptors, that regulate amblyopia. Less is known, however, about treatment-induced changes to those receptors and if those changes differentiate treatments that support the recovery of acuity versus persistent acuity deficits. Here we use an animal model to explore the effects of 3 visual treatments started during the CP (n=24, 10 male and 14 female); binocular vision (BV) that promotes good acuity versus reverse occlusion (RO) and binocular deprivation (BD) that causes persistent acuity deficits. We measured recovery of a collection of glutamatergic and GABAergic receptor subunits in V1 and modeled recovery of kinetics for NMDAR and GABAAR. There was a complex pattern of protein changes that prompted us to develop an unbiased data-driven approach for these high-dimensional data analyses to identify plasticity features and construct plasticity phenotypes. Cluster analysis of the plasticity phenotypes suggests that BV supports adaptive plasticity while RO and BD promote a maladaptive pattern. The RO plasticity phenotype appeared more similar to adults with high expression of GluA2 and the BD phenotypes were dominated by GABAAα1, highlighting that multiple plasticity phenotypes can underlie persistent poor acuity. After 2-4 days of BV the plasticity phenotypes resembled normals, but only one feature, the GluN2A:GluA2 balance, returned to normal levels. Perhaps, balancing Hebbian (GluN2A) and homeostatic (GluA2) mechanisms is necessary for the recovery of vision.

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Response to short-term deprivation of the human adult visual cortex measured with 7T BOLD

eLife ◽

10.7554/elife.40014 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 20

Author(s):

Paola Binda ◽

Jan W Kurzawski ◽

Claudia Lunghi ◽

Laura Biagi ◽

Michela Tosetti ◽

...

Keyword(s):

Visual Cortex ◽

Frequency Tuning ◽

Sensory Deprivation ◽

Ocular Dominance ◽

Monocular Deprivation ◽

Homeostatic Plasticity ◽

Short Term ◽

Structural Reorganization ◽

Parvocellular Pathway ◽

Human Adult

Sensory deprivation during the post-natal ‘critical period’ leads to structural reorganization of the developing visual cortex. In adulthood, the visual cortex retains some flexibility and adapts to sensory deprivation. Here we show that short-term (2 hr) monocular deprivation in adult humans boosts the BOLD response to the deprived eye, changing ocular dominance of V1 vertices, consistent with homeostatic plasticity. The boost is strongest in V1, present in V2, V3 and V4 but absent in V3a and hMT+. Assessment of spatial frequency tuning in V1 by a population Receptive-Field technique shows that deprivation primarily boosts high spatial frequencies, consistent with a primary involvement of the parvocellular pathway. Crucially, the V1 deprivation effect correlates across participants with the perceptual increase of the deprived eye dominance assessed with binocular rivalry, suggesting a common origin. Our results demonstrate that visual cortex, particularly the ventral pathway, retains a high potential for homeostatic plasticity in the human adult.

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Recovery of glutamatergic and GABAergic protein expression in visual cortex after monocular deprivation

10.1101/684191 ◽

2019 ◽

Author(s):

Justin L. Balsor ◽

David G. Jones ◽

Kathryn M. Murphy

Keyword(s):

Visual Cortex ◽

Protein Expression ◽

Binocular Vision ◽

Critical Period ◽

Visual Experience ◽

Monocular Deprivation ◽

The Other ◽

Synaptic Proteins ◽

Normal Expression ◽

Binocular Deprivation

AbstractA collection of glutamatergic and GABAergic proteins participate in regulating experience-dependent plasticity in the visual cortex (V1). Many studies have characterized changes to those proteins caused by monocular deprivation (MD) during the critical period (CP), but less is known about changes that occur when MD stops. We measured the effects of 3 types of visual experience after MD (n=24, 10 male and 14 female); reverse occlusion (RO), binocular deprivation (BD), or binocular vision, on the expression of synaptic proteins in V1 including glutamatergic and GABAergic receptor subunits. Synapsin expression was increased by RO but not affected by the other treatments. BD shifted the balance between glutamatergic and GABAergic receptor subunits to favor GABAAα1. In contrast, BV shifted expression to favor the glutamatergic mechanisms by increasing NMDAR and decreasing GABAAα1 subunits. None of the conditions returned normal expression levels to all of the proteins, but BV was the closest.

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Classification of Visual Cortex Plasticity Phenotypes following Treatment for Amblyopia

Neural Plasticity ◽

10.1155/2019/2564018 ◽

2019 ◽

Vol 2019 ◽

pp. 1-23 ◽

Cited By ~ 2

Author(s):

Justin L. Balsor ◽

David G. Jones ◽

Kathryn M. Murphy

Keyword(s):

Visual Cortex ◽

Critical Period ◽

Monocular Deprivation ◽

Data Driven ◽

Adaptive Plasticity ◽

Gabaergic Receptors ◽

Data Driven Approach ◽

Binocular Deprivation ◽

Induced Changes

Monocular deprivation (MD) during the critical period (CP) has enduring effects on visual acuity and the functioning of the visual cortex (V1). This experience-dependent plasticity has become a model for studying the mechanisms, especially glutamatergic and GABAergic receptors, that regulate amblyopia. Less is known, however, about treatment-induced changes to those receptors and if those changes differentiate treatments that support the recovery of acuity versus persistent acuity deficits. Here, we use an animal model to explore the effects of 3 visual treatments started during the CP (n=24, 10 male and 14 female): binocular vision (BV) that promotes good acuity versus reverse occlusion (RO) and binocular deprivation (BD) that causes persistent acuity deficits. We measured the recovery of a collection of glutamatergic and GABAergic receptor subunits in the V1 and modeled recovery of kinetics for NMDAR and GABAAR. There was a complex pattern of protein changes that prompted us to develop an unbiased data-driven approach for these high-dimensional data analyses to identify plasticity features and construct plasticity phenotypes. Cluster analysis of the plasticity phenotypes suggests that BV supports adaptive plasticity while RO and BD promote a maladaptive pattern. The RO plasticity phenotype appeared more similar to adults with a high expression of GluA2, and the BD phenotypes were dominated by GABAAα1, highlighting that multiple plasticity phenotypes can underlie persistent poor acuity. After 2-4 days of BV, the plasticity phenotypes resembled normals, but only one feature, the GluN2A:GluA2 balance, returned to normal levels. Perhaps, balancing Hebbian (GluN2A) and homeostatic (GluA2) mechanisms is necessary for the recovery of vision.

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