Retinal Ganglion Cell Mosaics Research Articles

Projection of Orthogonal Tiling from the Retina to the Visual Cortex

In higher mammals, the primary visual cortex (V1) is organized into diverse tuning maps of visual features. The topography of these maps intersects orthogonally, but it remains unclear how such a systematic relationship can develop. Here, we show that the orthogonal organization already exists in retinal ganglion cell (RGC) mosaics, providing a blueprint of the organization in V1. From analysis of the RGC mosaics data in monkeys and cats, we find that the ON-OFF RGC distance and ON-OFF angle of neighboring RGCs are organized into a topographic tiling across mosaics, analogous to the orthogonal intersection of cortical tuning maps. Our model simulation shows that the ON-OFF distance and angle in RGC mosaics correspondingly initiate ocular dominance/spatial frequency tuning and orientation tuning, resulting in the orthogonal intersection of cortical tuning maps. These findings suggest that the regularly structured ON-OFF patterns mirrored from the retina initiate the uniform representation of combinations of map features over the visual space.

Reduced mTORC1-signalling in retinal progenitor cells leads to visual pathway dysfunction.

ABSTRACTDevelopment of the vertebrate central nervous system involves the co-ordinated differentiation of progenitor cells and the establishment of functional neural networks. This neurogenic process is driven by both intracellular and extracellular cues that converge on the mammalian target of rapamycin complex 1 (mTORC1). Here we demonstrate that mTORC1-signalling mediates multi-faceted roles during central nervous system development using the mouse retina as a model system. Downregulation of mTORC1-signalling in retinal progenitor cells by conditional ablation of Rptor leads to proliferation deficits and an over-production of retinal ganglion cells during embryonic development. In contrast, reduced mTORC1-signalling in postnatal animals leads to temporal deviations in programmed cell death and the consequent production of asymmetric retinal ganglion cell mosaics and associated loss of axonal termination topographies in the dorsal lateral geniculate nucleus of adult mice. In combination these developmental defects induce visually mediated behavioural deficits. These collective observations demonstrate that mTORC1-signalling mediates critical roles during visual pathway development and function.

Optimal Information Transmission by Overlapping Retinal Cell Mosaics.

The retina provides an excellent system for understanding the trade-offs that influence distributed information processing across multiple neuron types. We focus here on the problem faced by the visual system of allocating a limited number neurons to encode different visual features at different spatial locations. The retina needs to solve three competing goals: 1) encode different visual features, 2) maximize spatial resolution for each feature, and 3) maximize accuracy with which each feature is encoded at each location. There is no current understanding of how these goals are optimized together. While information theory provides a platform for theoretically solving these problems, evaluating information provided by the responses of large neuronal arrays is in general challenging. Here we present a solution to this problem in the case where multi-dimensional stimuli can be decomposed into approximately independent components that are subsequently coupled by neural responses. Using this approach we quantify information transmission by multiple overlapping retinal ganglion cell mosaics. In the retina, translation invariance of input signals makes it possible to use Fourier basis as a set of independent components. The results reveal a transition where one high-density mosaic becomes less informative than two or more overlapping lower-density mosaics. The results explain differences in the fractions of multiple cell types, predict the existence of new retinal ganglion cell subtypes, relative distribution of neurons among cell types and differences in their nonlinear and dynamical response properties.

Interlayer Repulsion of Retinal Ganglion Cell Mosaics Regulates Spatial Organization of Functional Maps in the Visual Cortex.

In higher mammals, orientation tuning of neurons is organized into a quasi-periodic pattern in the primary visual cortex. Our previous model studies suggested that the topography of cortical orientation maps may originate from moiré interference of ON and OFF retinal ganglion cell (RGC) mosaics, but did not account for how the consistent spatial period of maps could be achieved. Here we address this issue with two crucial findings on the development of RGC mosaics: first, homotypic local repulsion between RGCs can develop a long-range hexagonal periodicity. Second, heterotypic interaction restrains the alignment of ON and OFF mosaics, and generates a periodic interference pattern map with consistent spatial frequency. To validate our model, we quantitatively analyzed the RGC mosaics in cat data, and confirmed that the observed retinal mosaics showed evidence of heterotypic interactions, contrary to the previous view that ON and OFF mosaics are developed independently.SIGNIFICANCE STATEMENT Orientation map is one of the most studied functional maps in the brain, but it has remained unanswered how the consistent spatial periodicity of maps could be developed. In the current study, we address this issue with our developmental model for the retinal origin of orientation map. We showed that local repulsive interactions between retinal ganglion cells (RGCs) can develop a hexagonal periodicity in the RGC mosaics and restrict the alignment between ON and OFF mosaics, so that they generate a periodic pattern with consistent spatial frequency for both the RGC mosaics and the cortical orientation maps. Our results demonstrate that the organization of functional maps in visual cortex, including its structural consistency, may be constrained by a retinal blueprint.

Local interaction in retinal ganglion cell mosaics can generate a consistent spatial periodicity in cortical functional maps

Orientation map is one of the most studied functional maps in visual cortex, but the developmental mechanism of its consistent spatial periodicity is still elusive. Recently, a theoretical model suggested that a moire interference pattern between ON and OFF retinal ganglion cell (RGC) mosaics can develop a quasi-periodic orientation map, but it is remained unclear how this can explain the constant periodicity of the maps [1]. Here we suggest a developmental model that a simple local interaction in RGCs can generate a consistent spatial periodicity of orientation preference, by inducing (i) a hexagonal lattice structure in ON/OFF RGC mosaics and (ii) a constant alignment angle between them. First, we introduced a developmental model of a monotypic RGC mosaic to show that a local repulsive interaction can generate a hexagonal structure (Figure ​(Figure1A).1A). Previously, in the model study of the pairwise interaction point process, it was suggested that a local interaction alone cannot develop a long-range order in the mosaic structure [2]. We assumed a different type of local repulsive interaction that the cell positions can be gradually shifted by a repulsion from the neighbor cells and confirmed that this model can develop a long-range ordered structure that is well fitted to a hexagonal lattice. Figure 1 Simulation of RGC mosaics and orientation map. A. Development of monotypic mosaic and auto-correlation. B. Heterotypic interaction depends on inter-layer distance. C. Moire interference pattern of ON/OFF RGC mosaics. D. Simulated orentation map. ... Next, we assumed that there also exists a heterotypic repulsive interaction between ON and OFF RGC mosaics and examined how this can affect the alignment between the two mosaics (Figure ​(Figure1B).1B). When the inter-layer distance between ON/OFF mosaics was varied within a proper interval, the hexagonal structure was preserved in each mosaic, but the alignment angle (θ) between the two mosaics was restricted within a certain range of angles, and this induced a constant spatial periodicity in the ON/OFF interference pattern (Figure ​(Figure1C).1C). As observed in the moire interference, we confirmed a consistent hexagonal periodicity in the cortical orientation map that are simulated by statistical wiring model from the developed RGC mosaics (Figure 1D,E) [3].

Retinal origin of orientation maps in visual cortex

The orientation map is a hallmark of primary visual cortex in higher mammals. It is not yet known how orientation maps develop, what function they play in visual processing and why some species lack them. Here we advance the notion that quasi-periodic orientation maps are established by moiré interference of regularly spaced ON and OFF-center retinal ganglion cell mosaics. A key prediction of the theory is that the centers of iso-orientation domains must be arranged in a hexagonal lattice on the cortical surface. Here we show that such pattern is observed in individuals of four different species: monkey, cat, tree shrew and ferret. The proposed mechanism explains how orientation maps can develop without requiring precise patterns of spontaneous activity or molecular guidance. Further, it offers a possible account for the emergence of orientation tuning in single neurons despite the absence of orderly orientation maps in rodents species.

Orientation maps as Moire interference of retinal ganglion cell mosaics

Orientation maps as Moire interference of retinal ganglion cell mosaics

On the origin of the functional architecture of the cortex.

The basic structure of receptive fields and functional maps in primary visual cortex is established without exposure to normal sensory experience and before the onset of the critical period. How the brain wires these circuits in the early stages of development remains unknown. Possible explanations include activity-dependent mechanisms driven by spontaneous activity in the retina and thalamus, and molecular guidance orchestrating thalamo-cortical connections on a fine spatial scale. Here I propose an alternative hypothesis: the blueprint for receptive fields, feature maps, and their inter-relationships may reside in the layout of the retinal ganglion cell mosaics along with a simple statistical connectivity scheme dictating the wiring between thalamus and cortex. The model is shown to account for a number of experimental findings, including the relationship between retinotopy, orientation maps, spatial frequency maps and cytochrome oxidase patches. The theory's simplicity, explanatory and predictive power makes it a serious candidate for the origin of the functional architecture of primary visual cortex.

Development of regular cellular spacing in the retina: theoretical models

During development of the nervous system, neurons should be appropriately positioned to enable them to make the right functional contacts. Neurons do not immediately migrate to their correct location, but instead regular arrangements gradually emerge from randomly arranged cell populations. This phenomenon has been studied often in the retina, due to its relatively simple layered organisation. In this review, I highlight the principal mechanisms that are thought to be involved, and how mathematical modelling has helped to further our understanding of the role of these processes upon mosaic formation. Three developmental mechanisms are studied in detail, namely, lateral migration, cell fate and cell death. As a case study, I then consider which mechanisms might be involved in the formation of retinal ganglion cell mosaics.

Exploring wavelet transforms for morphological differentiation between functionally different cat retinal ganglion cells

Cognition or higher brain activity is sometimes seen as a phenomenon greater than the sum of its parts. This viewpoint however is largely dependent on the state of the art of experimental techniques that endeavor to characterize morphology and its association to function. Retinal ganglion cells are readily accessible for this work and we discuss recent advances in computational techniques in identifying novel parameters that describe structural attributes possibly associated with specific function. These parameters are based on calculating wavelet gradients from cell images followed by the extraction of meaningful measures including 2nd wavelet moment, entropy of orientation, and curvature. For the three cell types analyzed, the mean 2nd wavelet moment, which relates to the field of influence of the dendritic-tree segments was significantly different. β cells had the highest mean 2nd wavelet moment, followed by the α and δ cells (134 ± 22, 93 ± 19 and 63 ± 12, respectively). There was no significant difference between cells for entropy of orientation, indicating no class with a preferential orientation of their dendritic tree. Curvature provided similar results to the 2nd wavelet moment with β cells having the highest curvature followed by α and the δ cells (mean ± SD: 161 ± 15; 134 ± 22; 121 ± 15). Our feature space analysis also indicated a difference between these cell types. No difference was found between the α and β cell types and their physiological counterparts the Y and X cells based on wavelet analysis. Both the X and Y cells can be divided into two subtypes, the ON- and OFF-center cells based on the stratification level of the dendritic tree within the retina. Using 2nd wavelet moment, a difference in their morphological attributes, not reported previously, was noted for these subtypes. The 2nd wavelet moment and curvature are further discussed with respect to explaining regularity of spacing and coverage associated with retinal ganglion cell mosaics.

Development and Organization of the Retina: From Molecules to Function

Development of Vision and the Pre-Visual System S.S. Easter, Jr., et al. Cellular and Molecular Aspects of Photoreceptor Differentiation R. Adler. Embryonic Patterning of Cone Subtypes in the Mammalian Retina K.C. Wikler, D.L. Stull. Development of Cone Distribution Patterns in Mammals A. Szel, et al. Genesis of Topographic and Cellular Diversity in the Primate Retina P. Rakic. Development of ON and OFF Retinal Ganglion Cell Mosaics L.M. Chalupa, et al. Getting to Grips with Neuronal Diversity: What is a Neuronal Type? J.E. Cook. Glio-Neuronal Interactions in Retinal Development A. Reichenbach. Comparative Anatomy and Function of Mammalian Horizontal Cells L. Peichl, et al. Parallel Pathways of Primate Vision: Sampling of Information in the Fourier Space by M and P Cells L. Peichl, et al. Parallel Pathways of Primate Vision: Sampling of Information in the Fourier Space by M and P Cells L.C.L. Silveira, H.D. De Mello, Jr. Transient and Persistent Na+, Ca2+, and Mixed-Cation Currents in Retinal Ganglion Cells A.T. Ishida. Synaptic Transmission Between Retinal Neurons M. Wilson. Scaling the Retina, Micro and Macro B.L. Finlay, R.L. Snow. Retinal Ganglion Cell Axonal Transport: Moving Down the Road to Functional Connections K.L. Moya. 5 Additional Articles. Index.

Species-dependent variation in the dendritic stratification of apparently homologous retinal ganglion cell mosaics in two neoteleost fishes

Large retinal ganglion cells of the marine neoteleost Bathymaster derjugini were labeled with horseradish peroxidase and studied in flatmounts. Four types formed regular, independent mosaics, of which three (biplexiform, alpha-a, alpha-c) resembled those in several other teleosts. The fourth (alpha-ab) appeared novel in one significant respect. Whereas we originally described similar cells in another neoteleost, Oreochromis spilurus, as monostratified in sublamina b of the inner plexiform layer, these were very clearly bistratified in a and b. Detailed re-analysis of our Oreochromis flatmounts showed that the difference is of one degree only: many Oreochromis cells do send fine dendrites into a. These observations strengthen the evidence that all four mosaics are homologous across a wide range of fishes, and clear away an obstacle to our earlier proposals that the alpha-a, alpha-ab and alpha-c mosaics of fishes, frogs, and perhaps other nonmammalian jawed vertebrates too, may all be homologous.

Spatial properties of retinal mosaics: an empirical evaluation of some existing measures.

Mosaics of neurons are usually quantified by methods based on nearest-neighbor distance (NND). The commonest indicator of regularity has been the ratio of the mean NND to the standard deviation, here termed the 'conformity ratio.' However, an accurate baseline value of this ratio for bounded random samples has never been determined; nor was its sampling distribution known, making it impossible to test its significance. Instead, significance was assessed from goodness-of-fit to a Rayleigh distribution, or from another ratio, that of the observed mean NND to an expected mean predicted by theory, termed the dispersion index. Neither approach allows for boundary effects that are common in experimental mosaics. Equally common are 'missing' neurons, whose effects on the statistics have not been studied. To address these deficiencies, random patterns and real neuronal mosaics were analyzed statistically. Ns independent random-point samples of size Np were generated for 13 Np values between 25 and 6400, where Ns x Np > or = 144,000. Samples were generated with rectangular boundaries of aspect ratio 1:1, 1:5, and 1:10 to examine the influence of sample geometry. NND distributions, conformity ratios, and dispersion indices were computed for the resulting 45,997 independent random patterns. From these, empirical sampling distributions and critical values were determined. NND distributions for small-to-medium, bounded, random populations were shown to differ significantly from Rayleigh distributions. Thus, goodness-of-fit tests are invalid for most experimental mosaics. Charts are presented from which the significance of conformity ratios or dispersion indices can be read directly. The conformity ratio reacts conservatively to extremes of sample geometry, and provides a useful and safe test. The dispersion index is nonconservative, making its use problematic. Tests based on the theoretical distribution of the dispersion index are unreliable for all but the largest samples. Random deletions were also made from 33 real retinal ganglion cell mosaics. The mean NND, conformity ratio, and dispersion index were determined for each original mosaic and 36 independent samples at each of nine sampling levels, retaining between 90% and 10% of the original population. An exclusion radius, based on a spatial autocorrelogram, was also calculated for each of these 10,725 mosaic samples. The mean NND was moderately insensitive to undersampling, rising smoothly. The exclusion radius was remarkably insensitive. The conformity ratio and dispersion index fell steeply, sometimes failing to reach significance while half of the cells still remained. For the same 33 original mosaics, linear regression showed the exclusion radius to be 62 +/- 3% of the mean NND.