Applying Super-Resolution and Tomography Concepts to Identify Receptive Field Subunits in the Retina.

Spatially nonlinear stimulus integration by retinal ganglion cells lies at the heart of various computations performed by the retina. It arises from the nonlinear transmission of signals that ganglion cells receive from bipolar cells, which thereby constitute functional subunits within a ganglion cell's receptive field. Inferring these subunits from recorded ganglion cell activity promises a new avenue for studying the functional architecture of the retina. This calls for efficient methods, which leave sufficient experimental time to leverage the acquired knowledge for further investigating identified subunits. Here, we combine concepts from super-resolution microscopy and computed tomography and introduce super-resolved tomographic reconstruction (STR) as a technique to efficiently stimulate and locate receptive field subunits. Simulations demonstrate that this approach can reliably identify subunits across a wide range of model variations, and application in recordings of primate parasol ganglion cells validates the experimental feasibility. STR can potentially reveal comprehensive subunit layouts within only a few tens of minutes of recording time, making it ideal for online analysis and closed-loop investigations of receptive field substructure in retina recordings.

Diversity of Ganglion Cell Responses to Saccade-Like Image Shifts in the Primate Retina.

Saccades are a fundamental part of natural vision. They interrupt fixations of the visual gaze and rapidly shift the image that falls onto the retina. These stimulus dynamics can cause activation or suppression of different retinal ganglion cells, but how they affect the encoding of visual information in different types of ganglion cells is largely unknown. Here, we recorded spiking responses to saccade-like shifts of luminance gratings from ganglion cells in isolated marmoset retinas and investigated how the activity depended on the combination of presaccadic and postsaccadic images. All identified cell types, On and Off parasol and midget cells, as well as a type of Large Off cells, displayed distinct response patterns, including particular sensitivity to either the presaccadic or the postsaccadic image or combinations thereof. In addition, Off parasol and Large Off cells, but not On cells, showed pronounced sensitivity to whether the image changed across the transition. Stimulus sensitivity of On cells could be explained based on their responses to step changes in light intensity, whereas Off cells, in particular, parasol and the Large Off cells, seem to be affected by additional interactions that are not triggered during simple light-intensity flashes. Together, our data show that ganglion cells in the primate retina are sensitive to different combinations of presaccadic and postsaccadic visual stimuli. This contributes to the functional diversity of the output signals of the retina and to asymmetries between On and Off pathways and provides evidence of signal processing beyond what is triggered by isolated steps in light intensity.SIGNIFICANCE STATEMENT Sudden eye movements (saccades) shift our direction of gaze, bringing new images in focus on our retinas. To study how retinal neurons deal with these rapid image transitions, we recorded spiking activity from ganglion cells, the output neurons of the retina, in isolated retinas of marmoset monkeys while shifting a projected image in a saccade-like fashion across the retina. We found that the cells do not just respond to the newly fixated image, but that different types of ganglion cells display different sensitivities to the presaccadic and postsaccadic stimulus patterns. Certain Off cells, for example, are sensitive to changes in the image across transitions, which contributes to differences between On and Off information channels and extends the range of encoded stimulus features.

Retinal Encoding of Natural Scenes.

An ultimate goal in retina science is to understand how the neural circuit of the retina processes natural visual scenes. Yet most studies in laboratories have long been performed with simple, artificial visual stimuli such as full-field illumination, spots of light, or gratings. The underlying assumption is that the features of the retina thus identified carry over to the more complex scenario of natural scenes. As the application of corresponding natural settings is becoming more commonplace in experimental investigations, this assumption is being put to the test and opportunities arise to discover processing features that are triggered by specific aspects of natural scenes. Here, we review how natural stimuli have been used to probe, refine, and complement knowledge accumulated under simplified stimuli, and we discuss challenges and opportunities along the way toward a comprehensive understanding of the encoding of natural scenes.

Simple model for encoding natural images by retinal ganglion cells with nonlinear spatial integration.

A central goal in sensory neuroscience is to understand the neuronal signal processing involved in the encoding of natural stimuli. A critical step towards this goal is the development of successful computational encoding models. For ganglion cells in the vertebrate retina, the development of satisfactory models for responses to natural visual scenes is an ongoing challenge. Standard models typically apply linear integration of visual stimuli over space, yet many ganglion cells are known to show nonlinear spatial integration, in particular when stimulated with contrast-reversing gratings. We here study the influence of spatial nonlinearities in the encoding of natural images by ganglion cells, using multielectrode-array recordings from isolated salamander and mouse retinas. We assess how responses to natural images depend on first- and second-order statistics of spatial patterns inside the receptive field. This leads us to a simple extension of current standard ganglion cell models. We show that taking not only the weighted average of light intensity inside the receptive field into account but also its variance over space can partly account for nonlinear integration and substantially improve response predictions of responses to novel images. For salamander ganglion cells, we find that response predictions for cell classes with large receptive fields profit most from including spatial contrast information. Finally, we demonstrate how this model framework can be used to assess the spatial scale of nonlinear integration. Our results underscore that nonlinear spatial stimulus integration translates to stimulation with natural images. Furthermore, the introduced model framework provides a simple, yet powerful extension of standard models and may serve as a benchmark for the development of more detailed models of the nonlinear structure of receptive fields.

Nonlinear Spatial Integration Underlies the Diversity of Retinal Ganglion Cell Responses to Natural Images.

How neurons encode natural stimuli is a fundamental question for sensory neuroscience. In the early visual system, standard encoding models assume that neurons linearly filter incoming stimuli through their receptive fields, but artificial stimuli, such as contrast-reversing gratings, often reveal nonlinear spatial processing. We investigated to what extent such nonlinear processing is relevant for the encoding of natural images in retinal ganglion cells in mice of either sex. We found that standard linear receptive field models yielded good predictions of responses to flashed natural images for a subset of cells but failed to capture the spiking activity for many others. Cells with poor model performance displayed pronounced sensitivity to fine spatial contrast and local signal rectification as the dominant nonlinearity. By contrast, sensitivity to high-frequency contrast-reversing gratings, a classical test for nonlinear spatial integration, was not a good predictor of model performance and thus did not capture the variability of nonlinear spatial integration under natural images. In addition, we also observed a class of nonlinear ganglion cells with inverse tuning for spatial contrast, responding more strongly to spatially homogeneous than to spatially structured stimuli. These findings highlight the diversity of receptive field nonlinearities as a crucial component for understanding early sensory encoding in the context of natural stimuli.SIGNIFICANCE STATEMENT Experiments with artificial visual stimuli have revealed that many types of retinal ganglion cells pool spatial input signals nonlinearly. However, it is still unclear how relevant this nonlinear spatial integration is when the input signals are natural images. Here we analyze retinal responses to natural scenes in large populations of mouse ganglion cells. We show that nonlinear spatial integration strongly influences responses to natural images for some ganglion cells, but not for others. Cells with nonlinear spatial integration were sensitive to spatial structure inside their receptive fields, and a small group of cells displayed a surprising sensitivity to spatially homogeneous stimuli. Traditional analyses with contrast-reversing gratings did not predict this variability of nonlinear spatial integration under natural images.

Personal health records in the preclinical medical curriculum: modeling student responses in a simple educational environment utilizing Google Health.

BACKGROUND: Various problems concerning the introduction of personal health records in everyday healthcare practice are reported to be associated with physicians' unfamiliarity with systematic means of electronically collecting health information about their patients (e.g. electronic health records--EHRs). Such barriers may further prevent the role physicians have in their patient encounters and the influence they can have in accelerating and diffusing personal health records (PHRs) to the patient community. One way to address these problems is through medical education on PHRs in the context of EHR activities within the undergraduate medical curriculum and the medical informatics courses in specific. In this paper, the development of an educational PHR activity based on Google Health is reported. Moreover, student responses on PHR's use and utility are collected and presented. The collected responses are then modelled to relate the satisfaction level of students in such a setting to the estimation about their attitude towards PHRs in the future. METHODS: The study was conducted by designing an educational scenario about PHRs, which consisted of student instruction on Google Health as a model PHR and followed the guidelines of a protocol that was constructed for this purpose. This scenario was applied to a sample of 338 first-year undergraduate medical students. A questionnaire was distributed to each one of them in order to obtain Likert-like scale data on the sample's response with respect to the PHR that was used; the data were then further analysed descriptively and in terms of a regression analysis to model hypothesised correlations. RESULTS: Students displayed, in general, satisfaction about the core PHR functions they used and they were optimistic about using them in the future, as they evaluated quite high up the level of their utility. The aspect they valued most in the PHR was its main role as a record-keeping tool, while their main concern was related to the negative effect their own opinion might have on the use of PHRs by patients. Finally, the estimate of their future attitudes towards PHR integration was found positively dependent of the level of PHR satisfaction that they gained through their experience (rho=0.524, p<0.001). CONCLUSIONS: The results indicate that students support PHRs as medical record keeping helpers and perceive them as beneficial to healthcare. They also underline the importance of achieving good educational experiences in improving PHR perspectives inside such educational activities. Further research is obviously needed to establish the relative long-term effect of education to other methods of exposing future physicians to PHRs.