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We employed high-resolution fMRI to distinguish the impacts of anisometropia and strabismus amblyopia on the evoked ocular dominance (OD) response. Sixteen amblyopic participants (eight females) plus eight individuals with normal vision (one female), participated in this study for whom we measured the difference between the response to stimulation of the two eyes, across areas V1-V4. In controls, the evoked OD response formed the expected striped pattern within V1. Compared to controls, the OD response in amblyopic participants formed larger fused patches that extended into downstream visual areas. Moreover, both anisometropic and strabismic participants showed elevated OD responses across V1-V4. Beyond these common effects, and despite similar densities of amblyopia between the two groups, strabismus, and anisometropia had differential impacts on the OD bias, binocular response, and correlation between V1 depth levels. Specifically, we found a greater increase in the size of the V1 portion that responded preferentially to fellow eye stimulation in anisometropic compared with strabismic individuals. We also found a greater difference between the amplitudes of the response to binocular stimulation, in those regions that responded preferentially to the fellow versus amblyopic eye, in anisometropic compared with strabismic participants. In contrast, strabismic participants demonstrated an increased correlation between the OD responses evoked within V1 superficial and deep depths, whereas anisometropic individuals did not. These results provide the primary direct functional evidence for distinct impacts of strabismus and anisometropia on the mesoscale functional organization of the human visual system, thus extending what was inferred previously about amblyopia from animal models., Competing Interests: The authors declare no competing financial interests., (Copyright © 2025 the authors.)

We studied the attributes of cytochrome c oxidase (CytOx)-rich blobs and ocular dominance columns (OD) in human V1 associated with monocular retinal lesions. Interblob distance, blob cross-sectional area, OD width, and OD arrangement pattern were analyzed in CytOx-reacted tangential sections of flat-mounted V1 preparations. Monocular deprivation induces differential expression of CytOx in the corresponding ODs in V1. We were thereby able to identify the V1 regions associated with the lesioned area in the retina, assign which OD was associated with each eye, and assign the corresponding blob in Layer III as deprived or nondeprived of visual input. We found that nondeprived blobs are more conspicuously stained than blobs outside the lesioned area. Notably, we found a selective expansion of blobs associated with the nonlesioned eye, whereas blobs associated with the deprived eye showed no significant change in size. Blob size in the latter condition was similar to the one observed in normal participants. These effects were present throughout the representation of the lesion in V1, suggesting that the underlying plasticity mechanisms do not depend on eccentricity. Retinal lesion caused no change in interblob distance, which was comparable to the normal brain (i.e., participants with no retinal lesion). This indicates that blob center is a stable hallmark of cortical organization. Finally, the width of ODs associated with the nonlesioned eye tended to be larger compared with ODs of the lesioned eye. However, this effect did not reach statistical significance. The stability of ODs thereby contrasts with blob plasticity, suggesting that the retinal lesion-triggered imbalance in the thalamocortical projection to Layer IVc has a limited impact on OD CytOx reactivity. On the other hand, we argue that ocular imbalance supports intracortical lateral competition that increases CytOx reactivity in the periblob region associated with the nonlesioned eye, accounting for the blob expansion we observe., (© 2024 Massachusetts Institute of Technology.)

A classic example of experience-dependent plasticity is ocular dominance (OD) shift, in which the responsiveness of neurons in the visual cortex is profoundly altered following monocular deprivation (MD). It has been postulated that OD shifts also modify global neural networks, but such effects have never been demonstrated. Here, we use wide-field fluorescence optical imaging (WFOI) to characterize calcium-based resting-state functional connectivity during acute (3 d) MD in female and male mice with genetically encoded calcium indicators ( Thy1 -GCaMP6f). We first establish the fundamental performance of WFOI by computing signal to noise properties throughout our data processing pipeline. Following MD, we found that Δ band (0.4-4 Hz) GCaMP6 activity in the deprived visual cortex decreased, suggesting that excitatory activity in this region was reduced by MD. In addition, interhemispheric visual homotopic functional connectivity decreased following MD, which was accompanied by a reduction in parietal and motor homotopic connectivity. Finally, we observed enhanced internetwork connectivity between the visual and parietal cortex that peaked 2 d after MD. Together, these findings support the hypothesis that early MD induces dynamic reorganization of disparate functional networks including the association cortices., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function, and plasticity. The poorly known "EE-derived signals'' mediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis reveals striking differences in intestinal bacteria composition between EE and standard rearing (ST) mice, as well as enhanced levels of short-chain fatty acids (SCFA) in EE mice. Depleting the microbiota of EE mice with antibiotics strongly decreases SCFA and prevents activation of adult ocular dominance plasticity, spine dynamics, and microglia rearrangement. SCFA treatment in ST mice mimics EE induction of ocular dominance plasticity and microglial remodeling. Remarkably, transferring the microbiota of EE mice to ST recipients activates adult ocular dominance plasticity. Thus, experience-dependent changes in gut microbiota regulate brain plasticity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Binocular vision is created by fusing the separate inputs arriving from the left and right eyes. 'Eye dominance' provides a measure of the perceptual dominance of one eye over the other. Theoretical models suggest that eye dominance is related to reciprocal inhibition between monocular units in the primary visual cortex, the first location where the binocular input is combined. As the specific inhibitory interactions in the binocular visual system critically depend on the presence of visual input, we sought to test the role of inhibition by measuring the inhibitory neurotransmitter GABA during monocular visual stimulation of the dominant and the non-dominant eye. GABA levels were measured in a single volume of interest in the early visual cortex, including V1 from both hemispheres, using a combined functional magnetic resonance imaging and magnetic resonance spectroscopy (combined fMRI-MRS) sequence on a 7-Tesla MRI scanner. Individuals with stronger eye dominance had a greater difference in GABAergic inhibition between the eyes. This relationship was present only when the visual system was actively processing sensory input and was not present at rest. We provide the first evidence that imbalances in GABA levels during ongoing sensory processing are related to eye dominance in the human visual cortex. Our finding supports the view that intracortical inhibition underlies normal eye dominance., (© 2021. The Author(s).)

In Long Evans rats, ocular dominance columns (ODCs) in V1 overlap with patches of callosal connections. Using anatomical tracers, we found that ODCs and callosal patches are present at postnatal day 10 (P10), several days before eye opening, and about 10 days before the activation of the critical period for ocular dominance plasticity (~P20). In rats monocularly enucleated at P10 and perfused ~P20, ODCs ipsilateral to the remaining eye desegregated, indicating that rat ODCs are highly susceptible to monocular enucleation during a precritical period. Monocular enucleation during the critical period exerted significant, although smaller, effects. Monocular eye lid suture during the critical period led to a significant expansion of the ipsilateral projection from the nondeprived eye, whereas the contralateral projection invaded into, and intermixed with, ipsilateral ODCs innervated by the deprived eye. We propose that this intermixing allows callosal connections to contribute to the effects of monocular deprivation assessed in the hemisphere ipsilateral to the nondeprived eye. The ipsilateral and contralateral projections from the deprived eye did not undergo significant shrinkage. In contrast, we found that callosal patches are less susceptible to imbalance of eye input. In rats monocularly enucleated during either the precritical or critical periods, callosal patches were maintained in the hemisphere ipsilateral to the remaining eye, but desegregated in the hemisphere ipsilateral to the enucleated orbit. Callosal patches were maintained in rats binocularly enucleated at P10 or later. Similarly, monocular deprivation during the critical period had no significant effect on callosal patches in either hemisphere., (© 2021 Wiley Periodicals LLC.)

Introduction: A variety of transgenic and knock-in mice that express mutant alleles of Amyloid precursor protein (APP) have been used to model the effects of amyloid-beta (Aβ) on circuit function in Alzheimer's disease (AD); however phenotypes described in these mice may be affected by expression of mutant APP or proteolytic cleavage products independent of Aβ. In addition, the effects of mutant APP expression are attributed to elevated expression of the amyloidogenic, 42-amino acid-long species of Aβ (Aβ42) associated with amyloid plaque accumulation in AD, though elevated concentrations of Aβ40, an Aβ species produced with normal synaptic activity, may also affect neural function., Methods: To explore the effects of elevated expression of Aβ on synaptic function in vivo, we assessed visual system plasticity in transgenic mice that express and secrete Aβ throughout the brain in the absence of APP overexpression. Transgenic mice that express either Aβ40 or Aβ42 were assayed for their ability to appropriately demonstrate ocular dominance plasticity following monocular deprivation., Results: Using two complementary approaches to measure the plastic response to monocular deprivation, we find that male and female mice that express either 40- or 42-amino acid-long Aβ species demonstrate a plasticity defect comparable to that elicited in transgenic mice that express mutant alleles of APP and Presenilin 1 (APP/PS1 mice)., Conclusions: These data support the hypothesis that mutant APP-driven plasticity impairment in mouse models of AD is mediated by production and accumulation of Aβ. Moreover, these findings suggest that soluble species of Aβ are capable of modulating synaptic plasticity, likely independent of any aggregation. These findings may have implications for the role of soluble species of Aβ in both development and disease settings., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The dorsal attention network (DAN) and the ventral attention network (VAN) are known to support visual attention, but the influences of ocular dominance on the attention networks are unclear. We aimed to explore how visual cortical asymmetry of the attention networks correlate with neurophysiological oscillation and connectivity markers of attentional processes., Methods: An oddball task with concentric circle stimuli of three different sizes (i.e., spot size of 5°, 20°, or 30° of visual angle) was used to vary task difficulty. Event-related oscillations and interareal communication were tested with an electroencephalogram-based visual evoked components as a function of ocular dominance in 30 healthy subjects., Results: Accuracy rates were higher in the dominant eyes compared with the nondominant eyes. Compared with the nondominant eyes, the dominant eyes had higher theta, low-alpha, and low-beta powers and lower high-alpha powers within the nodes of VAN and DAN. Furthermore, visual information processed by the dominant and nondominant eye had different fates, that is, the dominant eyes mainly relied on theta and low-alpha connectivity within both the VAN and the DAN, whereas the nondominant eyes mainly relied on theta connectivity within the VAN and high-alpha connectivity within the DAN. The difference in accuracy rate between the two eyes was correlated with the low-alpha oscillations in the anterior DAN area and low-alpha connectivity of the left DAN., Conclusions: The ocular dominance processing and interareal communication reveal a cortical asymmetry underlying attention, and this reflects a two-way modulatory mechanism within attention networks in the human brain.

Ultra-high field MRI can functionally image the cerebral cortex of human subjects at the submillimeter scale of cortical columns and laminae. Here, we investigate both in concert, by imaging ocular dominance columns (ODCs) in primary visual cortex (V1) across different cortical depths. We ensured that putative ODC patterns in V1 (a) are stable across runs, sessions, and scanners located in different continents, (b) have a width (~1.3 mm) expected from post-mortem and animal work and (c) are absent at the retinotopic location of the blind spot. We then dissociated the effects of bottom-up thalamo-cortical input and attentional feedback processes on activity in V1 across cortical depth. Importantly, the separation of bottom-up information flows into ODCs allowed us to validly compare attentional conditions while keeping the stimulus identical throughout the experiment. We find that, when correcting for draining vein effects and using both model-based and model-free approaches, the effect of monocular stimulation is largest at deep and middle cortical depths. Conversely, spatial attention influences BOLD activity exclusively near the pial surface. Our findings show that simultaneous interrogation of columnar and laminar dimensions of the cortical fold can dissociate thalamocortical inputs from top-down processing, and allow the investigation of their interactions without any stimulus manipulation., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The mammalian visual cortex contains multiple retinotopically defined areas that process distinct features of the visual scene. Little is known about what guides the functional differentiation of visual cortical areas during development. Recent studies in mice have revealed that visual input from the two eyes provides spatiotemporally distinct signals to primary visual cortex (V1), such that contralateral eye-dominated V1 neurons respond to higher spatial frequencies than ipsilateral eye-dominated neurons. To test whether binocular visual input drives the differentiation of visual cortical areas, we used two-photon calcium imaging to characterize the effects of juvenile monocular deprivation (MD) on the responses of neurons in V1 and two higher visual areas, LM (lateromedial) and PM (posteromedial). In adult mice of either sex, we find that MD prevents the emergence of distinct spatiotemporal tuning in V1, LM, and PM. We also find that, within each of these areas, MD reorganizes the distinct spatiotemporal tuning properties driven by the two eyes. Moreover, we find a relationship between speed tuning and ocular dominance in all three areas that MD preferentially disrupts in V1, but not in LM or PM. Together, these results reveal that balanced binocular vision during development is essential for driving the functional differentiation of visual cortical areas. The higher visual areas of mouse visual cortex may provide a useful platform for investigating the experience-dependent mechanisms that set up the specialized processing within neocortical areas during postnatal development. SIGNIFICANCE STATEMENT Little is known about the factors guiding the emergence of functionally distinct areas in the brain. Using in vivo Ca 2+ imaging, we recorded visually evoked activity from cells in V1 and higher visual areas LM (lateromedial) and PM (posteromedial) of mice. Neurons in these areas normally display distinct spatiotemporal tuning properties. We found that depriving one eye of normal input during development prevents the functional differentiation of visual areas. Deprivation did not disrupt the degree of speed tuning, a property thought to emerge in higher visual areas. Thus, some properties of visual cortical neurons are shaped by binocular experience, while others are resistant. Our study uncovers the fundamental role of binocular experience in the formation of distinct areas in visual cortex., (Copyright © 2021 the authors.)

Ocular dominance plasticity (ODP) is a type of cortical plasticity operating in visual cortex of mammals that are endowed with binocular vision based on the competition-driven disparity. Earlier, a molecular mechanism was proposed that catecholamines play an important role in the maintenance of ODP in kittens. Having survived the initial test, the hypothesis was further advanced to identify noradrenaline (NA) as a key factor that regulates ODP in the immature cortex. Later, the ODP-promoting effect of NA is extended to the adult with age-related limitations. Following the enhanced NA availability, the chain events downstream lead to the β-adrenoreceptor-induced cAMP accumulation, which in turn activates the protein kinase A. Eventually, the protein kinase translocates to the cell nucleus to activate cAMP responsive element binding protein (CREB). CREB is a cellular transcription factor that controls the transcription of various genes, underpinning neuronal plasticity and long-term memory. In the advent of molecular genetics in that various types of new tools have become available with relative ease, ODP research has lightly adopted in the rodent model the original concepts and methodologies. Here, after briefly tracing the strategic maturation of our quest, the review moves to the later development of the field, with the emphasis placed around the following issues: (a) Are we testing ODP per se? (b) What does monocular deprivation deprive of the immature cortex? (c) The critical importance of binocular competition, (d) What is the adult plasticity? (e) Excitation-Inhibition balance in local circuits, and (f) Species differences in the animal models., (© 2020 Wiley Periodicals LLC.)

Deep regions of the brain are not easily accessible to investigation at the mesoscale level in awake animals or humans. We have recently developed a functional ultrasound (fUS) technique that enables imaging hemodynamic responses to visual tasks. Using fUS imaging on two awake nonhuman primates performing a passive fixation task, we constructed retinotopic maps at depth in the visual cortex (V1, V2, and V3) in the calcarine and lunate sulci. The maps could be acquired in a single-hour session with relatively few presentations of the stimuli. The spatial resolution of the technology is illustrated by mapping patterns similar to ocular dominance (OD) columns within superficial and deep layers of the primary visual cortex. These acquisitions using fUS suggested that OD selectivity is mostly present in layer IV but with extensions into layers II/III and V. This imaging technology provides a new mesoscale approach to the mapping of brain activity at high spatiotemporal resolution in awake subjects within the whole depth of the cortex., Competing Interests: Competing interest statement: T.D. and M.T. are cofounders and T.D., M.T., and S.P. are shareholders of ICONEUS., (Copyright © 2020 the Author(s). Published by PNAS.)

Neuromodulatory systems are essential for remodeling glutamatergic connectivity during experience-dependent cortical plasticity. This permissive/enabling function of neuromodulators has been associated with their capacity to facilitate the induction of Hebbian forms of long-term potentiation (LTP) and depression (LTD) by affecting cellular and network excitability. In vitro studies indicate that neuromodulators also affect the expression of Hebbian plasticity in a pull-push manner: receptors coupled to the G-protein Gs promote the expression of LTP at the expense of LTD, and Gq-coupled receptors promote LTD at the expense of LTP. Here we show that pull-push mechanisms can be recruited in vivo by pairing brief monocular stimulation with pharmacological or chemogenetical activation of Gs- or Gq-coupled receptors to respectively enhance or reduce neuronal responses in primary visual cortex. These changes were stable, inducible in adults after the termination of the critical period for ocular dominance plasticity, and can rescue deficits induced by prolonged monocular deprivation., Competing Interests: SH, SH, DS, AK No competing interests declared, (© 2020, Hong et al.)

Since the discovery of ocular dominance plasticity, neuroscientists have understood that changes in visual experience during a discrete developmental time, the critical period, trigger robust changes in the visual cortex. State-of-the-art tools used to probe connectivity with cell-type-specific resolution have expanded the understanding of circuit changes underlying experience-dependent plasticity. Here, we review the visual circuitry of the mouse, describing projections from retina to thalamus, between thalamus and cortex, and within cortex. We discuss how visual circuit development leads to precise connectivity and identify synaptic loci, which can be altered by activity or experience. Plasticity extends to visual features beyond ocular dominance, involving subcortical and cortical regions, and connections between cortical inhibitory interneurons. Experience-dependent plasticity contributes to the alignment of networks spanning retina to thalamus to cortex. Disruption of this plasticity may underlie aberrant sensory processing in some neurodevelopmental disorders., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In albino rats, it has been reported that lateral striate cortex (V1) is highly binocular, and that input from the ipsilateral eye to this region comes through the callosum. In contrast, in Long Evans rats, this region is nearly exclusively dominated by the contralateral eye even though it is richly innervated by the callosum (Laing, Turecek, Takahata, & Olavarria, 2015). We hypothesized that the inability of callosal connections to relay ipsilateral eye input to lateral V1 in Long Evans rats is a consequence of the existence of ocular dominance columns (ODCs), and of callosal patches in register with ipsilateral ODCs in the binocular region of V1 (Laing et al., 2015). We therefore predicted that in albino rats input from both eyes intermix in the binocular region, without segregating into ODCs, and that callosal connections are not patchy. Confirming our predictions, we found that inputs from both eyes, studied with the transneuronal tracer WGA-HRP, are intermixed in the binocular zone of albinos, without segregating into ODCs. Similarly, we found that callosal connections in albino rats are not patchy but instead are distributed homogeneously throughout the callosal region in V1. We propose that these changes allow the transcallosal passage of ipsilateral eye input to lateral striate cortex, increasing its binocularity. Thus, the binocular region in V1 of albino rats includes lateral striate cortex, being therefore about 25% larger in area than the binocular region in Long Evans rats. Our findings provide insight on the role of callosal connections in generating binocular cells., (© 2019 Wiley Periodicals, Inc.)

C1q, the initiator of the classical complement cascade, mediates synapse elimination in the postnatal mouse dorsolateral geniculate nucleus of the thalamus and sensorimotor cortex. Here, we asked whether C1q plays a role in experience-dependent synaptic refinement in the visual system at later stages of development. The binocular zone of primary visual cortex (V1b) undergoes spine loss and changes in neuronal responsiveness following the closure of one eye during a defined critical period [a process referred to as ocular dominance plasticity (ODP)]. We therefore hypothesized that ODP would be impaired in the absence of C1q, and that V1b development would also be abnormal without C1q-mediated synapse elimination. However, when we examined several features of V1b development in mice lacking C1q, we found that the densities of most spine populations on basal and proximal apical dendrites, as well as firing rates and ocular dominance, were normal. C1q was only transiently required for the development of spines on apical, but not basal, secondary dendrites. Dendritic morphologies were also unaffected. Although we did not observe the previously described spine loss during ODP in either genotype, our results reveal that the animals lacking C1q had normal shifts in neuronal responsiveness following eye closure. Experiments were performed in both male and female mice. These results suggest that the development and plasticity of the mouse V1b is grossly normal in the absence of C1q. SIGNIFICANCE STATEMENT These findings illustrate that the development and experience-dependent plasticity of V1b is mostly normal in the absence of C1q, even though C1q has previously been shown to be required for developmental synapse elimination in the mouse visual thalamus as well as sensorimotor cortex. The V1b phenotypes in mice lacking C1q are more similar to the mild defects previously observed in the hippocampus of these mice, emphasizing that the contribution of C1q to synapse elimination appears to be dependent on context., (Copyright © 2020 the authors.)

The primary visual cortex contains a detailed map of retinal stimulus position (retinotopic map) and eye input (ocular dominance map) that results from the precise arrangement of thalamic afferents during cortical development. For reasons that remain unclear, the patterns of ocular dominance are very diverse across species and can take the shape of highly organized stripes, convoluted beads, or no pattern at all. Here, we use a new image-processing algorithm to measure ocular dominance patterns more accurately than in the past. We use these measurements to demonstrate that ocular dominance maps follow a common organizing principle that makes the cortical axis with the slowest retinotopic gradient orthogonal to the ocular dominance stripes. We demonstrate this relation in multiple regions of the primary visual cortex from individual animals, and different species. Moreover, consistent with the increase in the retinotopic gradient with visual eccentricity, we demonstrate a strong correlation between eccentricity and ocular dominance stripe width. We also show that an eye/polarity grid emerges within the visual cortical map when the representation of light and dark stimuli segregates along an axis orthogonal to the ocular dominance stripes, as recently demonstrated in cats. Based on these results, we propose a developmental model of visual cortical topography that sorts thalamic afferents by eye input and stimulus polarity, and then maximizes the binocular retinotopic match needed for depth perception and the light-dark retinotopic mismatch needed to process stimulus orientation. In this model, the different ocular dominance patterns simply emerge from differences in local retinotopic cortical topography. SIGNIFICANCE STATEMENT Thalamocortical afferents segregate in primary visual cortex by eye input and light-dark polarity. This afferent segregation forms cortical patterns that vary greatly across species for reasons that remain unknown. Here we show that the formation of ocular dominance patterns follows a common organizing principle across species that aligns the cortical axis of ocular dominance segregation with the axis of slowest retinotopic gradient. Based on our results, we propose a model of visual cortical topography that sorts thalamic afferents by eye input and stimulus polarity along orthogonal axes with the slowest and fastest retinotopic gradients, respectively. This organization maximizes the binocular retinotopic match needed for depth perception and the light-dark retinotopic mismatch needed to process stimulus orientation in carnivores and primates., (Copyright © 2019 the authors.)

A recent hemodynamic model is extended and applied to simulate and explore the feasibility of detecting ocular dominance (OD) and orientation preference (OP) columns in primary visual cortex by means of functional magnetic resonance imaging (fMRI). The stimulation entails a short oriented bar stimulus being presented to one eye and mapped to cortical neurons with corresponding OD and OP selectivity. Activated neurons project via patchy connectivity to excite other neurons with similar OP in nearby visual fields located preferentially along the direction of stimulus orientation. The resulting blood oxygen level dependent (BOLD) response is estimated numerically via the model's spatiotemporal hemodynamic response function. The results are then used to explore the feasibility of detecting spatial OD-OP modulation, either directly measuring BOLD or by using Wiener deconvolution to filter the image and estimate the underlying neural activity. The effect of noise is also considered and it is estimated that direct detection can be robust for fMRI resolution of around 0.5 mm, whereas detection with Wiener deconvolution is possible at a broader range from 0.125 mm to 1 mm resolution. The detection of OD-OP features is strongly dependent on hemodynamic parameters, such as low velocity and high damping reduce response spreads and result in less blurring. The short-bar stimulus that gives the most detectable response is found to occur when neural projections are at 45 relative to the edge of local OD boundaries, which provides a constraint on the OD-OP architecture even when it is not fully resolved., Competing Interests: The authors have declared that no competing interests exist.

Transplantation of even a small number of embryonic inhibitory neurons from the medial ganglionic eminence (MGE) into postnatal visual cortex makes it lose responsiveness to an eye deprived of vision when the transplanted neurons reach the age of the normal critical period of activity-dependent ocular dominance (OD) plasticity. The transplant might induce OD plasticity in the host circuitry or might instead construct a parallel circuit of its own to suppress cortical responses to the deprived eye. We transplanted MGE neurons expressing either archaerhodopsin or channelrhodopsin into the visual cortex of both male and female mice, closed one eyelid for 4-5 d, and, as expected, observed transplant-induced OD plasticity. This plasticity was evident even when the activity of the transplanted cells was suppressed or enhanced optogenetically, demonstrating that the plasticity was produced by changes in the host visual cortex. SIGNIFICANCE STATEMENT Interneuron transplantation into mouse V1 creates a window of heightened plasticity that is quantitatively and qualitatively similar to the normal critical period; that is, short-term occlusion of either eye markedly changes ocular dominance (OD). The underlying mechanism of this process is not known. Transplanted interneurons might either form a separate circuit to maintain the OD shift or might instead trigger changes in the host circuity. We designed experiments to distinguish the two hypotheses. Our findings suggest that while inhibition produced by the transplanted cells triggers this form of plasticity, the host circuity is entirely responsible for maintaining the OD shift., (Copyright © 2019 the authors.)

Perineuronal nets (PNNs) are condensed structures in the extracellular matrix that mainly surround GABA-ergic parvalbumin-positive interneurons in the adult brain. Previous studies revealed a parallel between PNN formation and the closure of the critical period. Moreover, ocular dominance plasticity is enhanced in response to PNN manipulations in adult animals. However, the mechanisms through which perineuronal nets modulate plasticity are still poorly understood. Recent work indicated that perineuronal nets may convey molecular signals by binding and storing proteins with important roles in cellular communication. Here we report that semaphorin3A (Sema3A), a chemorepulsive axon guidance cue known to bind to important perineuronal net components, is necessary to dampen ocular dominance plasticity in adult rats. First, we showed that the accumulation of Sema3A in PNNs in the visual cortex correlates with critical period closure, following the same time course of perineuronal nets maturation. Second, the accumulation of Sema3A in perineuronal nets was significantly reduced by rearing animals in the dark in the absence of any visual experience. Finally, we developed and characterized a tool to interfere with Sema3A signaling by means of AAV-mediated expression of receptor bodies, soluble proteins formed by the extracellular domain of the endogenous Sema3A receptor (neuropilin1) fused to a human IgG Fc fragment. By using this tool to antagonize Sema3A signaling in the adult rat visual cortex, we found that the specific inhibition of Sema3A promoted ocular dominance plasticity. Thus, Sema3A accumulates in perineuronal nets in an experience-dependent manner and its presence in the mature visual cortex inhibits plasticity.

Purpose: Retinitis pigmentosa is a family of genetic diseases inducing progressive photoreceptor degeneration. There is no cure for retinitis pigmentosa, but prospective therapeutic strategies are aimed at restoring or substituting retinal input. Yet, it is unclear whether the visual cortex of retinitis pigmentosa patients retains plasticity to react to the restored visual input., Methods: To investigate short-term visual cortical plasticity in retinitis pigmentosa, we tested the effect of short-term (2 hours) monocular deprivation on sensory ocular dominance (measured with binocular rivalry) in a group of 14 patients diagnosed with retinitis pigmentosa with a central visual field sparing greater than 20° in diameter., Results: After deprivation most patients showed a perceptual shift in ocular dominance in favor of the deprived eye (P < 0.001), as did control subjects, indicating a level of visual cortical plasticity in the normal range. The deprivation effect correlated negatively with visual acuity (r = -0.63, P = 0.015), and with the amplitude of the central 18° focal electroretinogram (r = -0.68, P = 0.015) of the deprived eye, revealing that in retinitis pigmentosa stronger visual impairment is associated with higher plasticity., Conclusions: Our results provide a new tool to assess the ability of retinitis pigmentosa patients to adapt to altered visual inputs, and suggest that in retinitis pigmentosa the adult brain has sufficient short-term plasticity to benefit from prospective therapies.

The non-cell autonomous transfer of OTX2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type and Otx2+/GFP mice at plastic and nonplastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. Cortical OTX2 infusion in juvenile mice induced Gadd45b/g expression through direct regulation of transcription. Intriguingly, a reverse effect was found in the adult, where reducing cortical OTX2 resulted in Gadd45b/g upregulation. Viral expression of Gadd45b in adult visual cortex directly induced ocular dominance plasticity with concomitant changes in MeCP2 foci within parvalbumin interneurons and in methylation states of several plasticity gene promoters, suggesting epigenetic regulation. This interaction provides a molecular mechanism for OTX2 to trigger critical period plasticity yet suppress adult plasticity., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

It is well established across many species that neurons in the primary visual cortex (V1) display preference for visual input from one eye or the other, which is termed ocular dominance (OD). In rodents, V1 neurons exhibit a strong bias toward the contralateral eye. Molecular mechanisms of how OD is established and later maintained by plastic changes are largely unknown. Here we report a novel role of an activity-dependent immediate early gene Homer1a (H1a) in these processes. Using both sexes of H1a knock-out (KO) mice, we found that there is basal reduction in the OD index of V1 neurons measured using intrinsic signal imaging. This was because of a reduction in the strength of inputs from the contralateral eye, which is normally dominant in mice. The abnormal basal OD index was not dependent on visual experience and is driven by postnatal expression of H1a. Despite this, H1a KOs still exhibited normal shifts in OD index following a short-term (2-3 d) monocular deprivation (MD) of the contralateral eye with lid suture. However, unlike wild-type counterparts, H1a KOs continued to shift OD index with a longer duration (5-6 d) of MD. The same phenotype was recapitulated in a mouse model that has reduced Homer1 binding to metabotropic glutamate receptor 5 (mGluR5). Our results suggest a novel role of H1a and its interaction with mGluR5 in strengthening contralateral eye inputs during postnatal development to establish normal contralateral bias in mouse V1 without much impact on OD shift with brief MD. SIGNIFICANCE STATEMENT Visual cortical neurons display varying degree of responsiveness to visual stimuli through each eye, which determines their ocular dominance (OD). Molecular mechanisms responsible for establishing normal OD are largely unknown. Development of OD has been shown to be largely independent of visual experience, but guided by molecular cues and spontaneous activity. We found that activity-dependent immediate early gene H1a is critical for establishing normal OD in V1 of mice, which show contralateral eye dominance. Despite the weaker contralateral bias, H1aKOs undergo largely normal OD plasticity. The basic phenotype of H1aKO was recapitulated by mGluR5 mutation that severely reduces H1a interaction. Our results suggest a novel role of mGluR5-H1a interaction in strengthening contralateral eye inputs to V1 during postnatal development., (Copyright © 2019 the authors.)

A few hours of monocular patching temporarily enhances the deprived eye's contribution to binocular vision, constituting a form of adult brain plasticity. Although the mechanism for this plasticity is currently unknown, several imaging studies present evidence that monocular deprivation achieves its effects by changing excitatory-inhibitory balance in the visual cortex. Much of the past work on adult monocular patching utilized binocular rivalry to quantify the patching-induced shift in perceptual eye dominance, extracting periods of exclusive visibility (in which one eye's signal is suppressed from perception) to assess each eye's contribution to binocular vision while overlooking the occurrence of mixed visibility (in which information from both eyes is combined). In this paper, we discuss two experiments to investigate the effects of short-term monocular occlusion on the relative predominance of mixed and exclusive percepts during binocular rivalry. In addition to the known perceptual eye-dominance shift, we hypothesized patching would also increase the perception of mixtures during rivalry due to deprivation-induced changes in excitatory-inhibitory balance. Our data point to two previously unknown effects of monocular deprivation: (a) a significant increase in the overall fraction and median duration of mixed visibility during rivalry that is detectable up to at least an hour after removing the patch and (b) the overall fraction of superimposition; rather than piecemeal, mixed percepts are specifically enhanced after monocular deprivation. In addition to strengthening the contribution of the deprived eye, our results show that temporary monocular patching enhances the visibility of fused binocular percepts, likely the result of attenuated interocular inhibition.

Optic nerve (ON) injury is an established model of axonal injury which results in retrograde degeneration and death of retinal ganglion cells as well anterograde loss of transmission and Wallerian degeneration of the injured axons. While the local impact of ON crush has been extensively documented we know comparatively little about the functional changes that occur in higher visual structures such as primary visual cortex (V1). We explored the extent of adult cortical plasticity using ON crush in aged mice. V1 function of the contralateral hemisphere was assessed longitudinally by intrinsic signal imaging and 2-photon calcium imaging before and after ON crush. Functional imaging demonstrated an immediate shift in V1 ocular dominance towards the ipsilateral, intact eye, due to the expected almost complete loss of responses to contralateral eye stimulation. Surprisingly, within 2 weeks we observed a delayed increase in ipsilateral eye responses. Additionally, spontaneous activity in V1 was reduced, similar to the lesion projection zone after retinal lesions. The observed changes in V1 activity indicate that severe ON injury in adulthood evokes cortical plasticity not only cross-modally but also within the visual cortex; this plasticity may be best compared with that seen after retinal lesions., (© The Author(s) 2019. Published by Oxford University Press.)

Objective: We hypothesized that the ocular dominance associated with brain asymmetry would influence macular structure. We assessed the structural asymmetry of the macula by ocular dominance., Methods: A total of 144 patients with no ophthalmic abnormalities were examined. After classifying eyes as dominant or non-dominant using the hole-in-a-card test, the macular ganglion cell inner plexiform layer and the macular thickness were measured in both groups using spectral domain optical coherence tomography, and we sought associations between ocular dominance and retinal thickness., Results: Ocular dominance was more frequently found in right eyes than in left eyes (68.75% vs 31.25%, respectively; p < 0.001). Using conditioned logistic regression, the right eye and the temporal-to-nasal retinal thickness ratio of the macular ganglion cell inner plexiform layer were selected as a final model for the determination of ocular dominance (p < 0.001, p = 0.013 respectively)., Conclusions: Macular vertical asymmetry was associated with ocular dominance. The macular structure and ocular dominance associated with visual cortex lateralization have functional and structural relationships., (Copyright © 2019 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Random noise can enhance the detectability of weak signals in nonlinear systems, a phenomenon known as stochastic resonance (SR). This concept is not only applicable to single threshold systems but can also be applied to dynamical systems with multiple attractor states, such as observed during the phenomenon of binocular rivalry. Binocular rivalry can be characterized by marginally stable attractor states between which the brain switches in a spontaneous, stochastic manner. Here we used a computational model to predict the effect of noise on perceptual dominance durations. Subsequently we compared the model prediction to a series of experiments where we measured binocular rivalry dynamics when noise (zero-mean Gaussian random noise) was added either to the visual stimulus (Exp. 1) or directly to the visual cortex (Exp. 2) by applying transcranial Random Noise Stimulation (tRNS 1 mA, 100-640 Hz zero -mean Gaussian random noise). We found that adding noise significantly reduced the mixed percept duration (Exp. 1 and Exp. 2). Our results are the first to demonstrate that both central and peripheral noise can influence state-switching dynamics of binocular rivalry under specific conditions (e.g. low visual contrast stimuli), in line with a SR-mechanism.

Ongoing internal cortical activity plays a major role in perception and behavior both in animals and humans. Previously we have shown that spontaneous patterns resembling orientation-maps appear over large cortical areas in the primary visual-cortex of anesthetized cats. However, it remains unknown 1) whether spontaneous-activity in the primate also displays similar patterns and 2) whether a significant difference exists between cortical ongoing-activity in the anesthetized and awake primate. We explored these questions by combining voltage-sensitive-dye imaging with multiunit and local-field-potential recordings. Spontaneously emerging orientation and ocular-dominance maps, spanning up to 6 × 6 mm2, were readily observed in anesthetized but not in awake monkeys. Nevertheless, spontaneous correlated-activity involving orientation-domains was observed in awake monkeys. Under both anesthetized and awake conditions, spontaneous correlated-activity coincided with traveling waves. We found that spontaneous activity resembling orientation-maps in awake animals spans smaller cortical areas in each instance, but over time it appears across all of V1. Furthermore, in the awake monkey, our results suggest that the synaptic strength had been completely reorganized including connections between dissimilar elements of the functional architecture. These findings lend support to the notion that ongoing-activity has many more fast switching representations playing an important role in cortical function and behavior.

In recent years, evidence has accumulated that non-Mendelian transgenerational inheritance of qualities acquired through experience is possible. In particular, it has been shown that raising rodents in a so-called enriched environment (EE) can not only modify the animals' behavior and increase their susceptibility to activity-dependent neuronal network changes, but also influences both behavior and neuronal plasticity of the non-enriched offspring. Here, we tested whether such a transgenerational transmission can also be observed in the primary visual cortex (V1) using ocular dominance (OD) plasticity after monocular deprivation (MD) as a paradigm. Whereas OD plasticity after 7 d of MD is absent in standard-cage (SC) raised mice beyond postnatal day (P)110, it is present lifelong in EE-raised mice. Using intrinsic signal optical imaging to visualize cortical activity, we confirm these previous observations and additionally show that OD plasticity is not only preserved in adult EE mice but also in their adult non-enriched offspring: mice born to enriched parents, but raised in SCs at least until P110 displayed similar OD shifts toward the open eye after 7 d of MD as age-matched EE-raised animals. Furthermore, testing the offspring of EE-female versus EE-males with SC-mating partners revealed that only pups of EE-females, but not of EE-males, preserved OD plasticity into adulthood, suggesting that the life experiences of the mother have a greater impact on the continued V1 plasticity of the offspring. The OD plasticity of the non-enriched pups of EE-mothers was, however, mechanistically different from that of non-enriched pups of EE-parents or EE mice.

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., Competing Interests: PB, JK, CL, LB, MT, MM No competing interests declared, (© 2018, Binda et al.)

Deprivation of visual information from one eye for a 120-minute period in normal adults results in a temporary strengthening of the patched eye's contribution to binocular vision. This plasticity for ocular dominance in adults has been demonstrated by binocular rivalry as well as binocular fusion tasks. Here, we investigate how its dynamics depend on the duration of the monocular deprivation. Using a binocular combination task, we measure the magnitude and recovery of ocular dominance change after durations of monocular deprivation ranging from 15 to 300 minutes. Surprisingly, our results show that the dynamics are of an all-or-none form. There was virtually no significant dependence on the duration of the initial deprivation.

The temporal closure of one eye in juvenile and young adult mice induces a shift of the ocular dominance (OD) of neurons in the binocular visual cortex. However, OD plasticity typically declines with age and is completely absent in matured mice beyond postnatal day (PD) 110. As it has been shown that the deprivation of one sensory input can induce neuronal alterations in non-deprived sensory cortices, we here investigated whether cross-modal interactions have the potential to reinstall OD plasticity in matured mice. Strikingly, using intrinsic signal imaging we could demonstrate that both whisker deprivation and auditory deprivation for only one week reinstated OD plasticity in fully adult mice. These OD shifts were always mediated by an increase of V1 responsiveness to visual stimulation of the open eye, a characteristic feature of OD plasticity normally only found in young adult mice. Moreover, systemic administration of the competitive NMDA receptor antagonist CPP completely abolished cross-modally induced OD plasticity. Taken together, we demonstrate here for the first time that the deprivation of non-visual senses has the potential to rejuvenate the adult visual cortex., (© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

In the absence of an optic chiasm, visual input to the right eye is represented in primary visual cortex (V1) in the right hemisphere, while visual input to the left eye activates V1 in the left hemisphere. Retinotopic mapping In V1 reveals that in each hemisphere left and right visual hemifield representations are overlaid (Hoffmann et al., 2012). To explain how overlapping hemifield representations in V1 do not impair vision, we tested the hypothesis that visual projections from nasal and temporal retina create interdigitated left and right visual hemifield representations in V1, similar to the ocular dominance columns observed in neurotypical subjects (Victor et al., 2000). We used high-resolution fMRI at 7T to measure the spatial distribution of responses to left- and right-hemifield stimulation in one achiasmic subject. T 2 -weighted 2D Spin Echo images were acquired at 0.8mm isotropic resolution. The left eye was occluded. To the right eye, a presentation of flickering checkerboards alternated between the left and right visual fields in a blocked stimulus design. The participant performed a demanding orientation-discrimination task at fixation. A general linear model was used to estimate the preference of voxels in V1 to left- and right-hemifield stimulation. The spatial distribution of voxels with significant preference for each hemifield showed interdigitated clusters which densely packed V1 in the right hemisphere. The spatial distribution of hemifield-preference voxels in the achiasmic subject was stable between two days of testing and comparable in scale to that of human ocular dominance columns. These results are the first in vivo evidence showing that visual hemifield representations interdigitate in achiasmic V1 following a similar developmental course to that of ocular dominance columns in V1 with intact optic chiasm., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recently, it has been shown that short-term monocular deprivation in adult humans can temporally shift the ocular dominance in favor of the deprived eye. It is not clear whether this form of ocular dominance plasticity can be explained by cortical contrast adaptation, which is known to be orientationally selective. Here we show that if only one eye is deprived of a limited band of orientations for a short period of 2.5 h, the deprived eye's contribution to binocular function at all orientations rather than just those corresponding to the previously deprived orientations is strengthened. This isotropic enhancement is quite different from the orientational enhancement previously reported and suggests a separate neuroplastic mechanism specific to binocular function., (Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.)

During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses within V1, specifically those containing the GABA A receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.

Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca 2+ imaging of thalamic afferents in layer 1 of binocular visual cortex, we provide evidence against this tenet: the respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced ocular dominance (OD) shifts after monocular deprivation in adult mice. Most (86%), but not all, of dLGN cell boutons were monocular during normal visual experience. Following deprivation, initially deprived-eye-dominated boutons reduced or lost their visual responsiveness to that eye and frequently became responsive to the non-deprived eye. This cannot be explained by eye-specific cortical changes propagating to dLGN via cortico-thalamic feedback because the shift in dLGN responses was largely resistant to cortical inactivation using the GABA A receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partially reflect plasticity of eye-specific inputs onto dLGN neurons.

In standard cage (SC) raised mice, experience-dependent ocular dominance (OD) plasticity in the primary visual cortex (V1) rapidly declines with age: in postnatal day 25-35 (critical period) mice, 4 days of monocular deprivation (MD) are sufficient to induce OD-shifts towards the open eye; thereafter, 7 days of MD are needed. Beyond postnatal day 110, even 14 days of MD failed to induce OD-plasticity in mouse V1. In contrast, mice raised in a so-called "enriched environment" (EE), exhibit lifelong OD-plasticity. EE-mice have more voluntary physical exercise (running wheels), and experience more social interactions (bigger housing groups) and more cognitive stimulation (regularly changed labyrinths or toys). Whether experience-dependent shifts of V1-activation happen faster in EE-mice and how long the plasticity promoting effect would persist after transferring EE-mice back to SCs has not yet been investigated. To this end, we used intrinsic signal optical imaging to visualize V1-activation i) before and after MD in EE-mice of different age groups (from 1-9 months), and ii) after transferring mice back to SCs after postnatal day 130. Already after 2 days of MD, and thus much faster than in SC-mice, EE-mice of all tested age groups displayed a significant OD-shift towards the open eye. Transfer of EE-mice to SCs immediately abolished OD-plasticity: already after 1 week of SC-housing and MD, OD-shifts could no longer be visualized. In an attempt to rescue abolished OD-plasticity of these mice, we either administered the anti-depressant fluoxetine (in drinking water) or supplied a running wheel in the SCs. OD-plasticity was only rescued for the running wheel- mice. Altogether our results show that raising mice in less deprived environments like large EE-cages strongly accelerates experience-dependent changes in V1-activation compared to the impoverished SC-raising. Furthermore, preventing voluntary physical exercise of EE-mice in adulthood immediately precludes OD-shifts in V1.

In amblyopia, a visual disorder caused by abnormal visual experience during development, the amblyopic eye (AE) loses visual sensitivity whereas the fellow eye (FE) is largely unaffected. Binocular vision in amblyopes is often disrupted by interocular suppression. We used 96-electrode arrays to record neurons and neuronal groups in areas V1 and V2 of six female macaque monkeys ( Macaca nemestrina ) made amblyopic by artificial strabismus or anisometropia in early life, as well as two visually normal female controls. To measure suppressive binocular interactions directly, we recorded neuronal responses to dichoptic stimulation. We stimulated both eyes simultaneously with large sinusoidal gratings, controlling their contrast independently with raised-cosine modulators of different orientations and spatial frequencies. We modeled each eye's receptive field at each cortical site using a difference of Gaussian envelopes and derived estimates of the strength of central excitation and surround suppression. We used these estimates to calculate ocular dominance separately for excitation and suppression. Excitatory drive from the FE dominated amblyopic visual cortex, especially in more severe amblyopes, but suppression from both the FE and AEs was prevalent in all animals. This imbalance created strong interocular suppression in deep amblyopes: increasing contrast in the AE decreased responses at binocular cortical sites. These response patterns reveal mechanisms that likely contribute to the interocular suppression that disrupts vision in amblyopes. SIGNIFICANCE STATEMENT Amblyopia is a developmental visual disorder that alters both monocular vision and binocular interaction. Using microelectrode arrays, we examined binocular interaction in primary visual cortex and V2 of six amblyopic macaque monkeys ( Macaca nemestrina ) and two visually normal controls. By stimulating the eyes dichoptically, we showed that, in amblyopic cortex, the binocular combination of signals is altered. The excitatory influence of the two eyes is imbalanced to a degree that can be predicted from the severity of amblyopia, whereas suppression from both eyes is prevalent in all animals. This altered balance of excitation and suppression reflects mechanisms that may contribute to the interocular perceptual suppression that disrupts vision in amblyopes., (Copyright © 2017 the authors 0270-6474/17/378216-11$15.00/0.)

The 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 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., Competing Interests: The authors declare no conflict of interest.

In the primary visual cortex of many mammals, ocular dominance columns segregate information from the two eyes. Yet under controlled conditions, most human observers are unable to correctly report the eye to which a stimulus has been shown, indicating that this information is lost during subsequent processing. This study investigates whether eye-of-origin information is available in the pattern of electrophysiological activity evoked by visual stimuli, recorded using EEG and decoded using multivariate pattern analysis. Observers (N=24) viewed sine-wave grating and plaid stimuli of different orientations, shown to either the left or right eye (or both). Using a support vector machine, eye-of-origin could be decoded above chance at around 140 and 220ms post stimulus onset, yet observers were at chance for reporting this information. Other stimulus features, such as binocularity, orientation, spatial pattern, and the presence of interocular conflict (i.e. rivalry), could also be decoded using the same techniques, though all of these were perceptually discriminable above chance. A control analysis found no evidence to support the possibility that eye dominance was responsible for the eye-of-origin effects. These results support a structural explanation for multivariate decoding of electrophysiological signals - information organised in cortical columns can be decoded, even when observers are unaware of this information., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Experiments on the adult visual cortex of cats, ferrets and monkeys have revealed organized spatial relationships between multiple feature maps which can also be reproduced by the Kohonen and elastic net self-organization models. However, attempts to apply these models to simulate the temporal kinetics of monocular deprivation (MD) during the critical period, and their effects on the spatial arrangement of feature maps, have led to conflicting results. In this study, we performed MD and chronic imaging in the ferret visual cortex during the critical period of ocular dominance (OD) plasticity. We also used the Kohonen model to simulate the effects of MD on OD and orientation map development. Both the experiments and simulations demonstrated two general parameter-insensitive findings. Specifically, our first finding demonstrated that the OD index shift resulting from MD, and its subsequent recovery during binocular vision (BV), were both nonlinear, with a significantly stronger shift occurring during the initial period. Meanwhile, spatial reorganization of feature maps led to globally unchanged but locally shifted map patterns. In detail, we found that the periodicity of OD and orientation maps remained unchanged during, and after, deprivation. Relationships between OD and orientation maps remained similar but were significantly weakened due to OD border shifts. These results indicate that orthogonal gradient relationships between maps may be preset and are only mildly modifiable during the critical period. The Kohonen model was able to reproduce these experimental results, hence its role is further extended to the description of cortical feature map dynamics during development., (Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.)

During the developmental critical period for visual plasticity, discordant vision alters the responsiveness of neurons in visual cortex. The subsequent closure of the critical period not only consolidates neural function but also limits recovery of acuity from preceding abnormal visual experience. Despite species-specific differences in circuitry of the visual system, these characteristics are conserved. The nogo-66 receptor 1 (ngr1) is one of only a small number of genes identified thus far that is essential to closing the critical period. Mice lacking a functional ngr1 gene retain developmental visual plasticity as adults and their visual acuity spontaneously improves after prolonged visual deprivation. Experiments employing conditional mouse genetics have revealed that ngr1 restricts plasticity within distinct circuits for ocular dominance and visual acuity. However, the mechanisms by which NgR1 limits plasticity have not been elucidated, in part because the subcellular localization and signal transduction of the protein are only partially understood. Here we explore potential mechanisms for NgR1 function in relation to manipulations that reactivate visual plasticity in adults and propose lines of investigation to address relevant gaps in knowledge., (© The Author(s) 2015.)

Maturation of excitatory drive onto fast-spiking interneurons (FS INs) in the visual cortex has been implicated in the control of the timing of the critical period for ocular dominance plasticity. However, the mechanisms that regulate the strength of these synapses over cortical development are not understood. Here we use a mouse model to show that neuregulin (NRG) and the receptor tyrosine kinase erbB4 regulate the timing of the critical period. NRG1 enhanced the strength of excitatory synapses onto FS INs, which inhibited ocular dominance plasticity during the critical period but rescued plasticity in transgenics with hypoexcitable FS INs. Blocking the effects of endogenous neuregulin via inhibition of erbBs rescued ocular dominance plasticity in postcritical period adults, allowing recovery from amblyopia induced by chronic monocular deprivation. Thus, the strength of excitation onto FS INs is a key determinant of critical period plasticity and is maintained at high levels by NRG-erbB4 signaling to constrain plasticity in adulthood., Significance Statement: Despite decades of experimentation, the mechanisms by which critical periods of enhanced synaptic plasticity are initiated and terminated are not completely understood. Here we show that neuregulin (NRG) and the receptor tyrosine kinase erbB4 determine critical period timing by controlling the strength of excitatory synapses onto FS INs. NRG1 enhanced excitatory drive onto fast spiking interneurons, which inhibited ocular dominance plasticity in juveniles but rescued plasticity in transgenics with hypoexcitable FS INs. Blocking the effects of endogenous neuregulin via inhibition of erbBs rescued ocular dominance plasticity in adults, allowing recovery from amblyopia induced by chronic monocular deprivation. Thus, in contrast to prevailing views of the termination of the critical period, active maintenance of strong excitation onto FS INs constrains plasticity in adults., (Copyright © 2016 the authors 0270-6474/16/3610285-11$15.00/0.)

Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear. Here we show that brief monocular deprivation during the critical period downregulates neuregulin-1(NRG1)/ErbB4 signaling in PV neurons, causing retraction of excitatory inputs to PV neurons. Exogenous NRG1 rapidly restores excitatory inputs onto deprived PV cells through downstream PKC-dependent activation and AMPA receptor exocytosis, thus enhancing PV neuronal inhibition to excitatory neurons. NRG1 treatment prevents the loss of deprived eye visual cortical responsiveness in vivo. Our findings reveal molecular, cellular, and circuit mechanisms of NRG1/ErbB4 in regulating the initiation of critical period visual cortical plasticity., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Binocular rivalry arises when incompatible images are presented to the two eyes. If the two eyes' conflicting features are invisible, leading to identical perceptual interpretations, does rivalry competition still occur? Here we investigated whether binocular rivalry can be induced from conflicting but invisible spatial patterns. A chromatic grating counterphase flickering at 30 Hz appeared uniform, but produced significant tilt aftereffect and orientation-selective adaptation. The invisible pattern also generated significant BOLD activities in the early visual cortex, with minimal response in the parietal and frontal cortical areas. Compared with perceptually matched uniform stimuli, a monocularly presented invisible chromatic grating enhanced the rivalry competition with a low-contrast visible grating presented to the other eye. Furthermore, switching from a uniform field to a perceptually matched invisible chromatic grating produced interocular suppression at approximately 200 ms after onset of the invisible grating. Experiments using briefly presented monocular probes revealed evidence for sustained rivalry competition between two invisible gratings during continuous dichoptic presentations. These findings indicate that even without visible interocular conflict, and with minimal engagement of frontoparietal cortex and consciousness related top-down feedback, perceptually identical patterns with invisible conflict features produce rivalry competition in the early visual cortex.

Purpose: To determine how formation of an acquired myopic crescent adjacent to the optic disc affects metabolic activity in the primary visual cortex., Design: Laboratory animal study., Participants: Three macaque monkeys., Methods: The blind spot region in the primary visual cortex was labeled by cytochrome oxidase (CO) histochemistry analysis or [(3)H]proline autoradiography., Main Outcome Measures: Visualization of the representation of the blind spot and myopic peripapillary crescent in the visual cortex., Results: In high myopia, a region resembling the myopic peripapillary crescent was visible in cortical sections processed for CO. In this region, metabolic activity was reduced in ocular dominance columns that normally would be driven by input from retina corresponding to the myopic peripapillary crescent., Conclusions: The formation of a myopic crescent is accompanied by loss of metabolic activity in the cortex supplied by the affected retina. This observation confirms that retinal tissue is damaged by the development of a myopic crescent, rather than simply translocated in a temporal direction. The cortical defect matches the myopic peripapillary crescent in size and shape, indicating that fill-in of the retinotopic map by healthy, surrounding retina does not occur., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Monocular deprivation evokes a prominent shift of neuronal responses in the visual cortex toward the open eye, accompanied by functional and structural synaptic rearrangements. This shift is reversible, but it is unknown whether the recovery happens at the level of individual neurons or whether it reflects a population effect. We used ratiometric Ca(2+) imaging to follow the activity of the same excitatory layer 2/3 neurons in the mouse visual cortex over months during repeated episodes of ocular dominance (OD) plasticity. We observed robust shifts toward the open eye in most neurons. Nevertheless, these cells faithfully returned to their pre-deprivation OD during binocular recovery. Moreover, the initial network correlation structure was largely recovered, suggesting that functional connectivity may be regained despite prominent experience-dependent plasticity., (Copyright © 2016, American Association for the Advancement of Science.)

The primary visual cortex contains a detailed map of the visual scene, which is represented according to multiple stimulus dimensions including spatial location, ocular dominance and stimulus orientation. The maps for spatial location and ocular dominance arise from the spatial arrangement of thalamic afferent axons in the cortex. However, the origins of the other maps remain unclear. Here we show that the cortical maps for orientation, direction and retinal disparity in the cat (Felis catus) are all strongly related to the organization of the map for spatial location of light (ON) and dark (OFF) stimuli, an organization that we show is OFF-dominated, OFF-centric and runs orthogonal to ocular dominance columns. Because this ON-OFF organization originates from the clustering of ON and OFF thalamic afferents in the visual cortex, we conclude that all main features of visual cortical topography, including orientation, direction and retinal disparity, follow a common organizing principle that arranges thalamic axons with similar retinotopy and ON-OFF polarity in neighbouring cortical regions.

In standard cage (SC)-raised mice, ocular dominance (OD) plasticity of the primary visual cortex (V1) induced by monocular deprivation (MD) is maximal in juveniles, declines in adults, and is absent beyond postnatal day (PD) 110. Raising mice in an enriched environment (EE) preserved a juvenile-like OD plasticity after 7 days of MD until at least PD196, mediated by reductions of deprived eye responses in V1. Whether the sensitive phase for OD plasticity can be prolonged into older age and whether long-term EE modifies visual abilities was not yet known. Here, we demonstrate that EE raising enables lifelong OD plasticity. In contrast to PD200 EE-mice, the preserved OD shift in both >PD400 and >PD700 EE-mice was mediated by increases in open eye responses in V1 (adult OD plasticity). When SC-mice were transferred to EE after PD110, OD plasticity was restored until PD922. Moreover, visual abilities tested by both optomotry and the visual water task and interindividual variability were not different between PD700 SC- and EE-mice. Taken together, EE raising enabled a lifelong OD plasticity but did not affect basic visual performance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Neuroimaging studies have shown that the dominant eye is linked preferentially to the ipsilateral primary visual cortex. However, its role in perception still is misunderstood. We examined the influence of eye dominance and eye dominance strength on saccadic parameters, contrasting stimulations presented in the two hemifields., Methods: Participants with contrasted eye dominance (left or right) and eye dominance strength (strong or weak) were asked to make a saccade toward a target displayed at 5° or 7° left or right of a fixation cross. In some trials, a distractor at 3° of eccentricity also was displayed either in the same hemifield as the target (to induce a global effect on saccade amplitude) or in the opposite hemifield (to induce a remote distractor effect on saccade latency)., Results: Eye dominance did influence saccade amplitude as participants with strong eye dominance showed more accurate saccades toward the target (weaker global effect) in the hemifield contralateral to the dominant eye than in the ipsilateral one. Such asymmetry was not found in participants with weak eye dominance or when a remote distractor was used., Conclusions: We show that eye dominance strength influences saccade target selection. We discuss several arguments supporting the view that such advantage may be linked to the relationship between the dominant eye and ipsilateral hemisphere. French Abstract.