Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Signatures of criticality arise in simple neural population models with correlations

Large-scale recordings of neuronal activity make it possible to gain insights into the collective activity of neural ensembles. It has been hypothesized that neural populations might be optimized to operate at a 'thermodynamic critical point', and that this property has implications for information processing. Support for this notion has come from a series of studies which identified statistical signatures of criticality in the ensemble activity of retinal ganglion cells. What are the underlying mechanisms that give rise to these observations? Here we show that signatures of criticality arise even in simple feed-forward models of retinal population activity. In particular, they occur whenever neural population data exhibits correlations, and is randomly sub-sampled during data analysis. These results show that signatures of criticality are not necessarily indicative of an optimized coding strategy, and challenge the utility of analysis approaches based on equilibrium thermodynamics for understanding partially observed biological systems.Comment: 36 pages, LaTeX; added journal reference on page 1, added link to code repositor

Streaming an image through the eye: The retina seen as a dithered scalable image coder

We propose the design of an original scalable image coder/decoder that is inspired from the mammalians retina. Our coder accounts for the time-dependent and also nondeterministic behavior of the actual retina. The present work brings two main contributions: As a first step, (i) we design a deterministic image coder mimicking most of the retinal processing stages and then (ii) we introduce a retinal noise in the coding process, that we model here as a dither signal, to gain interesting perceptual features. Regarding our first contribution, our main source of inspiration will be the biologically plausible model of the retina called Virtual Retina. The main novelty of this coder is to show that the time-dependent behavior of the retina cells could ensure, in an implicit way, scalability and bit allocation. Regarding our second contribution, we reconsider the inner layers of the retina. We emit a possible interpretation for the non-determinism observed by neurophysiologists in their output. For this sake, we model the retinal noise that occurs in these layers by a dither signal. The dithering process that we propose adds several interesting features to our image coder. The dither noise whitens the reconstruction error and decorrelates it from the input stimuli. Furthermore, integrating the dither noise in our coder allows a faster recognition of the fine details of the image during the decoding process. Our present paper goal is twofold. First, we aim at mimicking as closely as possible the retina for the design of a novel image coder while keeping encouraging performances. Second, we bring a new insight concerning the non-deterministic behavior of the retina.Comment: arXiv admin note: substantial text overlap with arXiv:1104.155

Photoreceptor Outer Segment-like Structures in Long-Term 3D Retinas from Human Pluripotent Stem Cells.

The retinal degenerative diseases, which together constitute a leading cause of hereditary blindness worldwide, are largely untreatable. Development of reliable methods to culture complex retinal tissues from human pluripotent stem cells (hPSCs) could offer a means to study human retinal development, provide a platform to investigate the mechanisms of retinal degeneration and screen for neuroprotective compounds, and provide the basis for cell-based therapeutic strategies. In this study, we describe an in vitro method by which hPSCs can be differentiated into 3D retinas with at least some important features reminiscent of a mature retina, including exuberant outgrowth of outer segment-like structures and synaptic ribbons, photoreceptor neurotransmitter expression, and membrane conductances and synaptic vesicle release properties consistent with possible photoreceptor synaptic function. The advanced outer segment-like structures reported here support the notion that 3D retina cups could serve as a model for studying mature photoreceptor development and allow for more robust modeling of retinal degenerative disease in vitro

Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies

Encoding of saccadic scene changes in the mouse retina

The task of the visual system is to extract behaviourally relevant information from the visual scene. A common strategy for most animals ranging from insects to humans is to constantly reposition gaze by making saccades within the scene. This ‘fixate and saccade’ strategy seems to pose a challenge, as it introduces a highly blurred image on the retina during a saccade, but at the same time acquires a ‘snapshot’ of the world during every fixation. The visual signals on the retina are thus segmented into brief image fixations separated by global motion. What is the response of a ganglion cell to ‘motion blur’ caused by a saccade, and how does it influence the response to subsequent fixations? Also, how does the global motion signal influence the response dynamics of a ganglion cell? In this thesis, we addressed these questions by two complementary approaches. First, we analysed the retinal ganglion cell responses to simulated saccades. We analysed two important aspects of the response - 1) response during a saccade-like motion, 2) response to fixation images. For about half of the recorded cells, we found strong spiking activity during the saccade. This supports the idea that the retina actively encodes the saccade and may signal the abrupt scene change to downstream brain areas. Furthermore, we characterized the responses to the newly fixated image. While there appears to be only little influence of the preceding motion signal itself on these responses, the responses depended strongly on the image content during the fixation period prior to the saccade. Thus, saccadic vision may provide ‘temporal context’ to each fixation, and ganglion cells encode image transitions rather than currently fixated images. Based on this perspective, we classified retinal ganglion cells into five response types, suggesting that the retina encodes at least five parallel channels of information under saccadic visual stimulation. The five response types identified in this study are as follows: 1) Classical Encoders - Response only to preferred stimuli; 2) Offset Detectors - Response only to the saccade; 3) Indifferent Encoders - Response to all fixated images; 4) Change Detectors - Response only when the new image after the saccade differs from the previous image; 5) Similarity Detectors - Response only when the new image after the saccade is similar to the previous image. Second, we analysed the influence of global motion signals on the response of a retinal ganglion cell to the stimulus in its receptive field. The stimulus beyond the receptive field is designated as remote stimulus. We chose simple stimulus that represent various configurations used in earlier studies, thus allowing us to compare our results. We show that the remote stimulus both enhances and suppresses the mean firing rate, but only suppresses the evoked activity. Furthermore, we show that the remote stimulus decreases the contrast sensitivity and modifies the response gain. Thus, the ganglion cells encode the stimulus in relation to the whole scene, rather than purely respond to the stimulus in the receptive field. Our results suggest that the global motion signals provide ‘spatial context’ to the response of the stimulus within the receptive field

Fast, scalable, Bayesian spike identification for multi-electrode arrays

We present an algorithm to identify individual neural spikes observed on high-density multi-electrode arrays (MEAs). Our method can distinguish large numbers of distinct neural units, even when spikes overlap, and accounts for intrinsic variability of spikes from each unit. As MEAs grow larger, it is important to find spike-identification methods that are scalable, that is, the computational cost of spike fitting should scale well with the number of units observed. Our algorithm accomplishes this goal, and is fast, because it exploits the spatial locality of each unit and the basic biophysics of extracellular signal propagation. Human intervention is minimized and streamlined via a graphical interface. We illustrate our method on data from a mammalian retina preparation and document its performance on simulated data consisting of spikes added to experimentally measured background noise. The algorithm is highly accurate

Organotypic Culture of Physiologically Functional Adult Mammalian Retinas

BACKGROUND: The adult mammalian retina is an important model in research on the central nervous system. Many experiments require the combined use of genetic manipulation, imaging, and electrophysiological recording, which make it desirable to use an in vitro preparation. Unfortunately, the tissue culture of the adult mammalian retina is difficult, mainly because of the high energy consumption of photoreceptors. METHODS AND FINDINGS: We describe an interphase culture system for adult mammalian retina that allows for the expression of genes delivered to retinal neurons by particle-mediated transfer. The retinas retain their morphology and function for up to six days— long enough for the expression of many genes of interest—so that effects upon responses to light and receptive fields could be measured by patch recording or multielectrode array recording. We show that a variety of genes encoding pre- and post-synaptic marker proteins are localized correctly in ganglion and amacrine cells. CONCLUSIONS: In this system the effects on neuronal function of one or several introduced exogenous genes can be studied within intact neural circuitry of adult mammalian retina. This system is flexible enough to be compatible with genetic manipulation, imaging, cell transfection, pharmacological assay, and electrophysiological recordings