Visual Deprivation during Mouse Critical Period Reorganizes Network-Level Functional Connectivity.

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.

Blockade of GluN2B-Containing NMDA Receptors Prevents Potentiation and Depression of Responses during Ocular Dominance Plasticity.

Monocular deprivation (MD) causes an initial decrease in synaptic responses to the deprived eye in juvenile mouse primary visual cortex (V1) through Hebbian long-term depression (LTD). This is followed by a homeostatic increase, which has been attributed either to synaptic scaling or to a slide threshold for Hebbian long-term potentiation (LTP) rather than scaling. We therefore asked in mice of all sexes whether the homeostatic increase during MD requires GluN2B-containing NMDA receptor activity, which is required to slide the plasticity threshold but not for synaptic scaling. Selective GluN2B blockade from 2-6 d after monocular lid suture prevented the homeostatic increase in miniature excitatory postsynaptic current (mEPSC) amplitude in monocular V1 of acute slices and prevented the increase in visually evoked responses in binocular V1 in vivo. The decrease in mEPSC amplitude and visually evoked responses during the first 2 d of MD also required GluN2B activity. Together, these results support the idea that GluN2B-containing NMDA receptors first play a role in LTD immediately following eye closure and then promote homeostasis during prolonged MD by sliding the plasticity threshold in favor of LTP.

Functional ultrasound imaging of deep visual cortex in awake nonhuman primates.

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.

Functional Differentiation of Mouse Visual Cortical Areas Depends upon Early Binocular Experience.

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 Ca2+ 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.

Principles underlying sensory map topography in primary visual cortex.

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.

Chronic Monocular Deprivation Reveals MMP9-Dependent and -Independent Aspects of Murine Visual System Plasticity.

The deletion of matrix metalloproteinase MMP9 is combined here with chronic monocular deprivation (cMD) to identify the contributions of this proteinase to plasticity in the visual system. Calcium imaging of supragranular neurons of the binocular region of primary visual cortex (V1b) of wild-type mice revealed that cMD initiated at eye opening significantly decreased the strength of deprived-eye visual responses to all stimulus contrasts and spatial frequencies. cMD did not change the selectivity of V1b neurons for the spatial frequency, but orientation selectivity was higher in low spatial frequency-tuned neurons, and orientation and direction selectivity were lower in high spatial frequency-tuned neurons. Constitutive deletion of MMP9 did not impact the stimulus selectivity of V1b neurons, including ocular preference and tuning for spatial frequency, orientation, and direction. However, MMP9-/- mice were completely insensitive to plasticity engaged by cMD, such that the strength of the visual responses evoked by deprived-eye stimulation was maintained across all stimulus contrasts, orientations, directions, and spatial frequencies. Other forms of experience-dependent plasticity, including stimulus selective response potentiation, were normal in MMP9-/- mice. Thus, MMP9 activity is dispensable for many forms of activity-dependent plasticity in the mouse visual system, but is obligatory for the plasticity engaged by cMD.

Ocular Dominance Plasticity in Binocular Primary Visual Cortex Does Not Require C1q.

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.

Ultra-high field fMRI reveals origins of feedforward and feedback activity within laminae of human ocular dominance columns.

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.

Impairment of visual cortical plasticity by amyloid-beta species.

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 (Aß) 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 Aß. In addition, the effects of mutant APP expression are attributed to elevated expression of the amyloidogenic, 42-amino acid-long species of Aß (Aß42) associated with amyloid plaque accumulation in AD, though elevated concentrations of Aß40, an Aß species produced with normal synaptic activity, may also affect neural function. METHODS: To explore the effects of elevated expression of Aß on synaptic function in vivo, we assessed visual system plasticity in transgenic mice that express and secrete Aß throughout the brain in the absence of APP overexpression. Transgenic mice that express either Aß40 or Aß42 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 Aß 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 Aß. Moreover, these findings suggest that soluble species of Aß are capable of modulating synaptic plasticity, likely independent of any aggregation. These findings may have implications for the role of soluble species of Aß in both development and disease settings.

Relationship of Sighting Ocular Dominance with Macular Photostress Test Time and Thickness of the Middle Macular Layers.

SIGNIFICANCE: The mechanisms of sighting ocular dominance, which is particularly important in monovision therapies and sports vision, are not fully understood yet. Whether the macula affects ocular dominance or ocular dominance affects the macula is also a subject of interest. PURPOSE: The aim of this study was to investigate the relationship of sighting ocular dominance with macular photostress test time and middle macular layer thickness. METHODS: One-hundred eyes of 50 healthy adult volunteers were included in this cross-sectional study. Sighting eye dominance was decided by a hole-in-the-card test. The macular photostress test was performed by exposing the eye to the ophthalmoscope light for 10 seconds and measuring the time taken to return to visual acuity within one row of pre-light exposure acuity. The spectral-domain optical coherence tomography examinations were performed to measure thickness of middle macular layers (i.e., outer nuclear, outer plexiform, inner nuclear, and inner plexiform). Refractive error and intraocular pressure (IOP) measurements were also recorded. RESULTS: The comparison of dominant and nondominant eyes in the aspect of refractive error, IOP, and macular photostress test time did not show statistically significant differences (P > .05). The thicknesses of macular outer nuclear, outer plexiform, inner nuclear, and inner plexiform layers were similar in the dominant and nondominant eyes (P > .05). In addition, macular photostress time was not statistically significantly correlated with the thickness of middle macular layers (P > .05). CONCLUSIONS: The thickness of middle macular layers and macular photostress recovery time are similar in dominant and nondominant eyes.

Homer1a Is Required for Establishment of Contralateral Bias and Maintenance of Ocular Dominance in Mouse Visual Cortex.

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.

Transplanted Cells Are Essential for the Induction But Not the Expression of Cortical Plasticity.

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.

Diversity of Ocular Dominance Patterns in Visual Cortex Originates from Variations in Local Cortical Retinotopy.

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.

Critical-period plasticity in the visual cortex.

In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the timing of the critical period. Although there is little doubt that the maturation of specific inhibitory circuits plays a key role in the opening of the critical period in the visual cortex, it is less clear what puts an end to it. In this review, we describe the established mechanisms and point out where more experimental work is needed. We also show that plasticity in the visual cortex is present well before, and long after, the peak of the critical period.

A hierarchical model of perceptual multistability involving interocular grouping.

Ambiguous visual images can generate dynamic and stochastic switches in perceptual interpretation known as perceptual rivalry. Such dynamics have primarily been studied in the context of rivalry between two percepts, but there is growing interest in the neural mechanisms that drive rivalry between more than two percepts. In recent experiments, we showed that split images presented to each eye lead to subjects perceiving four stochastically alternating percepts (Jacot-Guillarmod et al. Vision research, 133, 37-46, 2017): two single eye images and two interocularly grouped images. Here we propose a hierarchical neural network model that exhibits dynamics consistent with our experimental observations. The model consists of two levels, with the first representing monocular activity, and the second representing activity in higher visual areas. The model produces stochastically switching solutions, whose dependence on task parameters is consistent with four generalized Levelt Propositions, and with experiments. Moreover, dynamics restricted to invariant subspaces of the model demonstrate simpler forms of bistable rivalry. Thus, our hierarchical model generalizes past, validated models of binocular rivalry. This neuromechanistic model also allows us to probe the roles of interactions between populations at the network level. Generalized Levelt's Propositions hold as long as feedback from the higher to lower visual areas is weak, and the adaptation and mutual inhibition at the higher level is not too strong. Our results suggest constraints on the architecture of the visual system and show that complex visual stimuli can be used in perceptual rivalry experiments to develop more detailed mechanistic models of perceptual processing.

Feasibility of functional magnetic resonance imaging of ocular dominance and orientation preference in primary visual cortex.

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.

Dynamic Patterns of Spontaneous Ongoing Activity in the Visual Cortex of Anesthetized and Awake Monkeys are Different.

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.

Non-cell Autonomous OTX2 Homeoprotein Regulates Visual Cortex Plasticity Through Gadd45b/g.

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.

Plasticity in Adult Mouse Visual Cortex Following Optic Nerve Injury.

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.

Difference in myopia progression between dominant and non-dominant eye in patients with intermittent exotropia.

OBJECTIVE: To investigate the difference in the rate of myopia progression between the dominant and non-dominant eye in patients with intermittent exotropia (IXT). METHODS: We retrospectively reviewed the medical records of 33 patients who underwent surgery and later reoperation for IXT. We included only patients whose spherical equivalent refractive errors (SER) were ≤ - 0.50 diopter (D) in at least one eye at the time of reoperation. The main outcome measurement was the rate of myopia progression, which was defined as the mean annual change in SER between the first and second surgery. We classified patients into two groups: group A, which comprised 25 patients whose non-dominant eyes showed a faster myopia progression than their dominant eyes, and group B, which comprised the remaining 8 patients showing the opposite. RESULTS: Mean age of the patients at the time of the initial surgery was 5.64 years. Mean interval between the initial and second surgery was 4.45 years. Mean rate of myopia progression over the interval was - 0.37 D/year in the dominant eyes and - 0.50 D/year in the non-dominant eyes (P < 0.001). Group A had a significantly greater amount of distance deviation (31.0 vs. 25.6 PD, P = 0.020) and near deviation (30.8 vs 26.0 PD, P = 0.039) before the initial surgery and a significantly worse score of distance control (3.05 vs. 2.00, P = 0.023) before the second surgery than group B. CONCLUSIONS: The non-dominant eyes experienced a faster myopia progression than the dominant eyes in patients with IXT. This faster myopia progression demonstrated in the non-dominant eyes was associated with clinically severe exotropia in terms of the amount of deviation and the degree of control.