Erratum: Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes.

This corrects the article 10.3791/66272.

Motion-Acuity Test for Visual Field Acuity Measurement with Motion-Defined Shapes.

The standard visual acuity measurements rely on stationary stimuli, either letters (Snellen charts), vertical lines (vernier acuity) or grating charts, processed by those regions of the visual system most sensitive to the stationary stimulation, receiving visual input from the central part of the visual field. Here, an acuity measurement is proposed based on discrimination of simple shapes, that are defined by motion of the dots in the random dot kinematograms (RDK) processed by visual regions sensitive to motion stimulation and receiving input also from the peripheral visual field. In the motion-acuity test, participants are asked to distinguish between a circle and an ellipse, with matching surfaces, built from RDKs, and separated from the background RDK either by coherence, direction, or velocity of dots. The acuity measurement is based on ellipse detection, which with every correct response becomes more circular until reaching the acuity threshold. The motion-acuity test can be presented in negative contrast (black dots on white background) or in positive contrast (white dots on black background). The motion defined shapes are located centrally within 8 visual degrees and are surrounded by RDK background. To test the influence of visual peripheries on centrally measured acuity, a mechanical narrowing of the visual field to 10 degrees is proposed, using opaque goggles with centrally located holes. This easy and replicable narrowing system is suitable for MRI protocols, allowing further investigations of the functions of the peripheral visual input. Here, a simple measurement of shape and motion perception simultaneously is proposed. This straightforward test assesses vision impairments depending on the central and peripheral visual field inputs. The proposed motion-acuity test advances the capability of standard tests to reveal spare or even strengthened vision functions in patients with injured visual system, that until now remained undetected.

Motion-Based Acuity Task: Full Visual Field Measurement of Shape and Motion Perception.

Purpose: Damage of retinal representation of the visual field affects its local features and the spared, unaffected parts. Measurements of visual deficiencies in ophthalmological patients are separated for central (shape) or peripheral (motion and space perception) properties, and acuity tasks rely on stationary stimuli. We explored the benefit of measuring shape and motion perception simultaneously using a new motion-based acuity task. Methods: Eight healthy control subjects, three patients with retinitis pigmentosa (RP; tunnel vision), and 2 patients with Stargardt disease (STGD) juvenile macular degeneration were included. To model the peripheral loss, we narrowed the visual field in controls to 10 degrees. Negative and positive contrast of motion signals were tested in random-dot kinematograms (RDKs), where shapes were separated from the background by the motion of dots based on coherence, direction, or velocity. The task was to distinguish a circle from an ellipse. The difficulty of the task increased as ellipse became more circular until reaching the acuity limit. Results: High velocity, negative contrast was more difficult for all, and for patients with STGD, it was too difficult to participate. A slower velocity improved acuity for all participants. Conclusions: Proposed acuity testing not only allows for the full assessment of vision but also advances the capability of standard testing with the potential to detect spare visual functions. Translational Relevance: The motion-based acuity task might be a practical tool for assessing vision loss and revealing undetected, undamaged, or strengthened properties of the injured visual system by standard testing, as suggested here for two patients with STGD and three patients with RP.

BDNF expression in cat striate cortex is regulated by binocular pattern deprivation.

Deprivation of patterned visual information, as in early onset congenital cataract patients, results in a severe impairment in global motion perception. Previously we reported a delayed maturation of the peripheral visual field representation in primary visual area 17, based on a 2-D DIGE screen for protein expression changes and in situ hybridization for the activity reporter gene ZIF268. To corroborate these findings we here explore the binocular pattern deprivation (BD)-regulated expression of brain-derived neurotrophic factor (BDNF), a well-described neurotrophin precipitously regulated by early visual experience. To assess the timing of maturation-related BDNF expression we compared the central and the peripheral visual field representations of area 17 of 1, 2, 4 and 6-month-old and adult cats reared under normal visual conditions. To scrutinize the outcome of BD, four different deprivation strategies were compared, including early onset BD from birth and lasting for 2, 4 or 6 months (2BD, 4BD, 6BD), and late onset BD for 2 months upon 2 months of normal vision (2N2BD), as animal models of congenital and delayed onset cataract. During normal cortical development the BDNF transcript levels, measured by quantitative RT-PCR, remained stable. Higher BDNF mRNA levels were found in central area 17 of 2BD and 6BD animals compared to age-matched controls. In central area 17, the high BDNF mRNA levels at the end of the BD period may activate a mechanism by which plastic processes, halted by deprivation, may begin. We here confirm that the peripheral visual field representation of area 17 matures slower than its central counterpart. Only in central area 17 normal visual input upon BD could upregulate BDNF mRNA which may lead to a fast activation of local plastic adaptations.

Plasticity Beyond V1: Reinforcement of Motion Perception upon Binocular Central Retinal Lesions in Adulthood.

Induction of a central retinal lesion in both eyes of adult mammals is a model for macular degeneration and leads to retinotopic map reorganization in the primary visual cortex (V1). Here we characterized the spatiotemporal dynamics of molecular activity levels in the central and peripheral representation of five higher-order visual areas, V2/18, V3/19, V4/21a,V5/PMLS, area 7, and V1/17, in adult cats with central 10° retinal lesions (both sexes), by means of real-time PCR for the neuronal activity reporter gene zif268. The lesions elicited a similar, permanent reduction in activity in the center of the lesion projection zone of area V1/17, V2/18, V3/19, and V4/21a, but not in the motion-driven V5/PMLS, which instead displayed an increase in molecular activity at 3 months postlesion, independent of visual field coordinates. Also area 7 only displayed decreased activity in its LPZ in the first weeks postlesion and increased activities in its periphery from 1 month onward. Therefore we examined the impact of central vision loss on motion perception using random dot kinematograms to test the capacity for form from motion detection based on direction and velocity cues. We revealed that the central retinal lesions either do not impair motion detection or even result in better performance, specifically when motion discrimination was based on velocity discrimination. In conclusion, we propose that central retinal damage leads to enhanced peripheral vision by sensitizing the visual system for motion processing relying on feedback from V5/PMLS and area 7.SIGNIFICANCE STATEMENT Central retinal lesions, a model for macular degeneration, result in functional reorganization of the primary visual cortex. Examining the level of cortical reactivation with the molecular activity marker zif268 revealed reorganization in visual areas outside V1. Retinotopic lesion projection zones typically display an initial depression in zif268 expression, followed by partial recovery with postlesion time. Only the motion-sensitive area V5/PMLS shows no decrease, and even a significant activity increase at 3 months post-retinal lesion. Behavioral tests of motion perception found no impairment and even better sensitivity to higher random dot stimulus velocities. We demonstrate that the loss of central vision induces functional mobilization of motion-sensitive visual cortex, resulting in enhanced perception of moving stimuli.

Binocular pattern deprivation interferes with the expression of proteins involved in primary visual cortex maturation in the cat.

BACKGROUND: Binocular pattern deprivation from eye opening (early BD) delays the maturation of the primary visual cortex. This delay is more pronounced for the peripheral than the central visual field representation within area 17, particularly between the age of 2 and 4 months [Laskowska-Macios, Cereb Cortex, 2014]. RESULTS: In this study, we probed for related dynamic changes in the cortical proteome. We introduced age, cortical region and BD as principal variables in a 2-D DIGE screen of area 17. In this way we explored the potential of BD-related protein expression changes between central and peripheral area 17 of 2- and 4-month-old BD (2BD, 4BD) kittens as a valid parameter towards the identification of brain maturation-related molecular processes. Consistent with the maturation delay, distinct developmental protein expression changes observed for normal kittens were postponed by BD, especially in the peripheral region. These BD-induced proteomic changes suggest a negative regulation of neurite outgrowth, synaptic transmission and clathrin-mediated endocytosis, thereby implicating these processes in normal experience-induced visual cortex maturation. Verification of the expression of proteins from each of the biological processes via Western analysis disclosed that some of the transient proteomic changes correlate to the distinct behavioral outcome in adult life, depending on timing and duration of the BD period [Neuroscience 2013;255:99-109]. CONCLUSIONS: Taken together, the plasticity potential to recover from BD, in relation to ensuing restoration of normal visual input, appears to rely on specific protein expression changes and cellular processes induced by the loss of pattern vision in early life.

Are visual peripheries forever young?

The paper presents a concept of lifelong plasticity of peripheral vision. Central vision processing is accepted as critical and irreplaceable for normal perception in humans. While peripheral processing chiefly carries information about motion stimuli features and redirects foveal attention to new objects, it can also take over functions typical for central vision. Here I review the data showing the plasticity of peripheral vision found in functional, developmental, and comparative studies. Even though it is well established that afferent projections from central and peripheral retinal regions are not established simultaneously during early postnatal life, central vision is commonly used as a general model of development of the visual system. Based on clinical studies and visually deprived animal models, I describe how central and peripheral visual field representations separately rely on early visual experience. Peripheral visual processing (motion) is more affected by binocular visual deprivation than central visual processing (spatial resolution). In addition, our own experimental findings show the possible recruitment of coarse peripheral vision for fine spatial analysis. Accordingly, I hypothesize that the balance between central and peripheral visual processing, established in the course of development, is susceptible to plastic adaptations during the entire life span, with peripheral vision capable of taking over central processing.

Zif268 mRNA Expression Patterns Reveal a Distinct Impact of Early Pattern Vision Deprivation on the Development of Primary Visual Cortical Areas in the Cat.

Pattern vision deprivation (BD) can induce permanent deficits in global motion perception. The impact of timing and duration of BD on the maturation of the central and peripheral visual field representations in cat primary visual areas 17 and 18 remains unknown. We compared early BD, from eye opening for 2, 4, or 6 months, with late onset BD, after 2 months of normal vision, using the expression pattern of the visually driven activity reporter gene zif268 as readout. Decreasing zif268 mRNA levels between months 2 and 4 characterized the normal maturation of the (supra)granular layers of the central and peripheral visual field representations in areas 17 and 18. In general, all BD conditions had higher than normal zif268 levels. In area 17, early BD induced a delayed decrease, beginning later in peripheral than in central area 17. In contrast, the decrease occurred between months 2 and 4 throughout area 18. Lack of pattern vision stimulation during the first 4 months of life therefore has a different impact on the development of areas 17 and 18. A high zif268 expression level at a time when normal vision is restored seems to predict the capacity of a visual area to compensate for BD.

Lack of early pattern stimulation prevents normal development of the alpha (Y) retinal ganglion cell population in the cat.

Binocular deprivation of pattern vision (BD) early in life permanently impairs global motion perception. With the SMI-32 antibody against neurofilament protein (NFP) as a marker of the motion-sensitive Y-cell pathway (Van der Gucht et al. [2001] Cereb. Cortex 17:2805-2819), we analyzed the impact of early BD on the retinal circuitry in adult, perceptually characterized cats (Burnat et al. [2005] Neuroreport 16:751-754). In controls, large retinal ganglion cells exhibited a strong NFP signal in the soma and in the proximal parts of the dendritic arbors. The NFP-immunoreactive dendrites typically branched into sublamina a of the inner plexiform layer (IPL), i.e., the OFF inner plexiform sublamina. In the retina of adult BD cats, however, most of the NFP-immunoreactive ganglion cell dendrites branched throughout the entire IPL. The NFP-immunoreactive cell bodies were less regularly distributed, often appeared in pairs, and had a significantly larger diameter compared with NFP-expressing cells in control retinas. These remarkable differences in the immunoreactivity pattern were typically observed in temporal retina. In conclusion, we show that the anatomical organization typical of premature Y-type retinal ganglion cells persists into adulthood even if normal visual experience follows for years upon an initial 6-month period of BD. Binocular pattern deprivation possibly induces a lifelong OFF functional domination, normally apparent only during development, putting early high-quality vision forward as a premise for proper ON-OFF pathway segregation. These new observations for pattern-deprived animals provide an anatomical basis for the well-described motion perception deficits in congenital cataract patients.

Influence of binocular competition on the expression profiles of CRMP2, CRMP4, Dyn I, and Syt I in developing cat visual cortex.

The visual cortex is vulnerable to changes in visual input, especially during the critical period when numerous molecules drive the refinement of the circuitry. From a list of potential actors identified in a recent proteomics study, we selected 2 collapsin response mediator proteins (CRMP2/CRMP4) and 2 synaptic proteins, Dynamin I (Dyn I) and Synaptotagmin I (Syt I), for in-depth analysis of their developmental expression profile in cat visual cortex. CRMP2 and CRMP4 levels were high early in life and clearly declined toward adulthood. In contrast, Dyn I expression levels progressively augmented during maturation. Syt I showed low levels at eye opening and in adults, high levels around the peak of the critical period, and maximal levels at juvenile age. We further determined a role for each molecule in ocular dominance plasticity. CRMP2 and Syt I levels decreased in area 17 upon monocular deprivation, whereas CRMP4 and Dyn I levels remained unaffected. In contrast, binocular removal of pattern vision had no influence on CRMP2 and Syt I expression in kitten area 17. This study illustrates that not the loss of quality of vision through visual deprivation, but disruption of normal binocular visual experience is crucial to induce the observed molecular changes.

Age- and experience-dependent expression of dynamin I and synaptotagmin I in cat visual system.

Dynamin I (Dyn I) and Synaptotagmin I (Syt I) are essential for endocytosis-exocytosis processes, thus for neurotransmission. Despite their related function at presynaptic terminals, Dyn I and Syt I displayed opposite expression patterns during visual cortex maturation in the cat. Dyn I was more abundantly expressed in adults, while Syt I exhibited higher levels in kittens of postnatal day 30 (P30). In area 17 this developmental difference was most obvious in layers II/III. Layer VI displayed a strong hybridization signal for both molecules, independent of age. In addition, Syt I levels were higher in posterior compared to anterior area 17 in adult subjects. Moreover, in higher-order visual areas Syt I was unevenly distributed over the cortical layers, thereby setting clear areal boundaries in mature cortex. In contrast, Dyn I was rather homogeneously distributed over extrastriate areas at both ages. Both molecules thus demonstrated a widespread but different distribution and an opposite temporal expression pattern during visual system development. Notably, monocular deprivation during the critical period of ocular dominance plasticity significantly decreased Syt I expression levels in area 17 ipsilateral to the deprived eye, while no effect was observed on Dyn I expression. We therefore conclude that visual experience induces changes in Syt I expression that may reflect changes in constitutive exocytosis involved in postnatal structural refinements of the visual cortex. On the other hand, the spatial and temporal expression patterns of Dyn I correlate with the establishment and maintenance of the mature neuronal structure rather than neurite remodeling.

Neurofilament protein and neuronal activity markers define regional architectonic parcellation in the mouse visual cortex.

This study was designed to assess the chemoarchitectural organization and extent of the mouse visual cortex. We used nonphosphorylated neurofilament protein, a neuronal marker that exhibits region-specific cellular and laminar patterns, to delineate cortical subdivisions. A comprehensive analysis demonstrated that pyramidal and nonpyramidal neurons expressing neurofilament proteins display striking laminar and regional patterns in the mouse visual cortex permitting the delineation of the primary visual cortex (V1) and its monocular and binocular zones, 2 lateral, and 5 medial extrastriate cortical areas with clear anatomical boundaries and providing evidence that the mouse medial extrastriate cortex is not homogeneous. We also investigated the expression profiles of 2 neuronal activity markers, the immediate early genes c-fos and zif-268, following deprivation paradigms to ascertain the visual nature of all subdivisions caudal, medial, and lateral to V1. The present data indicate that neurochemically identifiable subdivisions of the mouse visual cortex exist laterally and medially to V1 and reveal specific anatomical and functional characteristics at the cellular and regional levels.

Development and plasticity-related changes in protein expression patterns in cat visual cortex: a fluorescent two-dimensional difference gel electrophoresis approach.

During early postnatal brain development, changes in visual input can lead to specific alteration of function and connectivity in mammalian visual cortex. In cat, this so-called critical period exhibits maximal sensory-driven adaptations around postnatal day 30 (P30), and ceases toward adulthood. We examined the molecular framework that directs age- and experience-dependent plasticity in cat visual cortex, by comparing protein expression profiles at eye opening (postnatal day 10 (P10), when experience-dependent plasticity starts), the peak of the critical period (P30), and in adulthood. Using 2-D DIGE, we performed comparisons of P10-P30 and P30-adult brain protein samples. Sixty protein spots showed statistically significant intensity changes in at least one comparison. Fifty-one spots were identified using quadrupole-TOF MS/MS or LC-MS/MS, containing 37 different proteins. The progressive increase or decrease in protein expression levels could be correlated to age-dependent postnatal brain development. Four spots containing transferrin, 14-3-3 alpha/beta and cypin, showed maximal protein expression levels at P30, thereby showing a positive correlation to critical period plasticity. Western analysis indeed revealed a clear effect of visual deprivation on cypin expression in cat visual cortex. Our results therefore demonstrate the power of 2-D DIGE as a tool toward understanding the molecular basis of nervous system development and plasticity.

Age-dependent alterations in CRMP2 and CRMP4 protein expression profiles in cat visual cortex.

We monitored the protein expression profiles of collapsin response mediator protein 2 and 4 (CRMP2 and CRMP4) throughout cat primary visual area 17 at different postnatal ages. Single immunocytochemical stainings revealed a clear effect of cortical maturation on the spatial and laminar distribution profile of CRMP2 and CRMP4. In kittens of postnatal day 10 (P10) and 30 (P30), CRMP2 and CRMP4 immunoreactivity was exclusively present in fibers running perpendicular to the cortical surface and crossing all cortical layers, but was never found in neuronal cell bodies. The immunoreactive fibers were embedded in an intensely and homogeneously stained neuropil. In contrast, mature visual cortex immunocytochemistry located CRMP2 and CRMP4 in the somatodendritic compartment of neurons with a clear CRMP-specific lamination pattern. Similar to kitten, neuropil staining was clearly observed but showed a decreasing gradient from layer I to VI in adult area 17. Detailed analysis of cellular morphology and size classified the CRMP2- and CRMP4-immunopositive cells in distinct neuronal populations. Double labeling of CRMP2 or CRMP4 with the typical interneuron marker parvalbumin (PV) showed many double-labeled cells immunoreactive for CRMP4 and PV, but not for CRMP2 and PV, corroborating the cell type-specific character of each CRMP. Our present results clearly illustrate that CRMP2 and CRMP4 may play an important role in visual cortex, possibly providing different classes of neurons with the potential to form a functionally meaningful network, not only during development, but also in adulthood, coincident with the belief that CRMPs are involved in neurite growth and guidance.

Global form perception in cats early deprived of pattern vision.

Recently, we showed that binocularly deprived cats are not able to detect global motion in a random dot pattern (Burnat et al., 2002). Here, we examined, in these animals, a global form discrimination task, that is, distinction of a square from a rectangle, matched for total surface. In contrast to the previously tested motion task, binocularly-deprived cats, as compared with controls, performed only at higher thresholds. Interestingly, the increase of the stimuli's surface, or a shift from horizontal to vertical orientation of the rectangle, significantly impaired their performance. We therefore conclude that binocularly-deprived cats do not attend to the global form of the stimuli. Instead, they spontaneously choose a local cue to discriminate and are not able to modify it.

Global motion detection is impaired in cats deprived early of pattern vision.

We investigated global motion detection in binocularly deprived cats (BD cats) and control cats (C cats). The cats were trained in the two-choice free running apparatus for a food reward. The positive stimulus was a moving random-dot pattern with all dots moving in one direction, the negative stimulus was the same random-dot pattern but stationary. The BD cats were severely impaired in detection of global motion stimulus as compared with the C cats. In contrast, their level of performance in a simple relative motion detection task (one square) did not differ from that in the C cats. However, in more complex relative motion detection task (two squares) the performance of the BD cats was impaired. The deficit in the detection of global motion in BD cats may be due to impairments of their Y-pathway.