Annual Review of Vision Science - Volume 4, 2018

I was drawn into research in George Wald's laboratory at Harvard, where as an undergraduate and graduate student, I studied vitamin A deficiency and dark adaptation. A chance observation while an assistant professor at Harvard led to the major research of my career—to understand the functional organization of vertebrate retinas. I started with a retinal circuit analysis of the primate retina with Brian Boycott and intracellular retinal cell recordings in mudpuppies with Frank Werblin. Subsequent pharmacology studies with Berndt Ehinger primarily with fish focused on dopamine and neuromodulation. Using zebrafish, we studied retinal development, neuronal connectivity, and the effects of genetic mutations on retinal structure and function. Now semi-retired, I have returned to primate retinal circuitry, undertaking a connectomic analysis of the human fovea in Jeffrey Lichtman's laboratory.

The small RNA regulatory molecules called microRNAs (miRNAs) play key roles in the development of most organisms. The expression of many different miRNAs has been described in the developing and mature vertebrate retina. The ability of miRNAs to regulate a diversity of messenger RNA targets allows them to have effects on many different developmental processes, but the functions of only a few miRNAs have been documented to date. Developmental transitions between cell states appear to be particularly sensitive to miRNA loss of function, as evidenced by specific miRNA knockdowns or from global perturbations in miRNA levels (e.g., Dicer deletion). However, we are still in only the very early stages of understanding the range of cellular functions miRNAs control during development.

Microglia, the primary resident immune cell type, constitute a key population of glia in the retina. Recent evidence indicates that microglia play significant functional roles in the retina at different life stages. During development, retinal microglia regulate neuronal survival by exerting trophic influences and influencing programmed cell death. During adulthood, ramified microglia in the plexiform layers interact closely with synapses to maintain synaptic structure and function that underlie the retina's electrophysiological response to light. Under pathological conditions, retinal microglia participate in potentiating neurodegeneration in diseases such as glaucoma, retinitis pigmentosa, and age-related neurodegeneration by producing proinflammatory neurotoxic cytokines and removing living neurons via phagocytosis. Modulation of pathogenic microglial activation states and effector mechanisms has been linked to neuroprotection in animal models of retinal diseases. These findings have led to the design of early proof-of-concept clinical trials with microglial modulation as a therapeutic strategy.

Electrical synaptic transmission via gap junctions underlies direct and rapid neuronal communication in the central nervous system. The diversity of functional roles played by electrical synapses is perhaps best exemplified in the vertebrate retina, in which gap junctions are expressed by each of the five major neuronal types. These junctions are highly plastic; they are dynamically regulated by ambient illumination and circadian rhythms acting through light-activated neuromodulators. The networks formed by electrically coupled neurons provide plastic, reconfigurable circuits positioned to play key and diverse roles in the transmission and processing of visual information at every retinal level. Recent work indicates gap junctions also play a role in the progressive cell death and aberrant activity seen in various pathological conditions of the retina. Gap junctions thus form potential targets for novel neuroprotective therapies in the treatment of neurodegenerative retinal diseases such as glaucoma and ischemic retinopathies.

This article was withdrawn on October 15, 2020, at the request of the journal editors, with agreement from the authors, owing to a substantial amount of unattributed or improperly cited text overlap with other sources. In accordance with Annual Reviews' commitment to transparency, the original PDF of the article remains available for download at https://www.annualreviews.org/doi/pdf/10.1146/annurev-vision-091517-034018.

We know a good deal about the operation of the retina when either rod or cone photoreceptors provide the dominant input (i.e., under very dim or very bright conditions). However, we know much less about how the retina operates when rods and cones are coactive (i.e., under intermediate lighting conditions, such as dusk). Such mesopic conditions span 20–30% of the light levels over which vision operates and encompass many situations in which vision is essential (e.g., driving at night). These lighting conditions are challenging because rod and cone signals differ substantially: Rod responses are nearing saturation, while cone responses are weak and noisy. A rich history of perceptual studies guides our investigation of how the retina operates under mesopic conditions and in doing so provides a powerful opportunity to link general issues about parallel processing in neural circuits with computation and perception. We review some of the successes and challenges in understanding the retinal basis of perceptual rod-cone interactions.

Motion in the visual world provides critical information to guide the behavior of sighted animals. Furthermore, as visual motion estimation requires comparisons of signals across inputs and over time, it represents a paradigmatic and generalizable neural computation. Focusing on the Drosophila visual system, where an explosion of technological advances has recently accelerated experimental progress, we review our understanding of how, algorithmically and mechanistically, motion signals are first computed.

Visual motion on the retina activates a cohort of retinal ganglion cells (RGCs). This population activity encodes multiple streams of information extracted by parallel retinal circuits. Motion processing in the retina is best studied in the direction-selective circuit. The main focus of this review is the neural basis of direction selectivity, which has been investigated in unprecedented detail using state-of-the-art functional, connectomic, and modeling methods. Mechanisms underlying the encoding of other motion features by broader RGC populations are also discussed. Recent discoveries at both single-cell and population levels highlight the dynamic and stimulus-dependent engagement of multiple mechanisms that collectively implement robust motion detection under diverse visual conditions.

The perceptual consequences of eye movements are manifold: Each large saccade is accompanied by a drop of sensitivity to luminance-contrast, low-frequency stimuli, impacting both conscious vision and involuntary responses, including pupillary constrictions. They also produce transient distortions of space, time, and number, which cannot be attributed to the mere motion on the retinae. All these are signs that the visual system evokes active processes to predict and counteract the consequences of saccades. We propose that a key mechanism is the reorganization of spatiotemporal visual fields, which transiently increases the temporal and spatial uncertainty of visual representations just before and during saccades. On one hand, this accounts for the spatiotemporal distortions of visual perception; on the other hand, it implements a mechanism for fusing pre- and postsaccadic stimuli. This, together with the active suppression of motion signals, ensures the stability and continuity of our visual experience.

Our vision depends upon shifting our high-resolution fovea to objects of interest in the visual field. Each saccade displaces the image on the retina, which should produce a chaotic scene with jerks occurring several times per second. It does not. This review examines how an internal signal in the primate brain (a corollary discharge) contributes to visual continuity across saccades. The article begins with a review of evidence for a corollary discharge in the monkey and evidence from inactivation experiments that it contributes to perception. The next section examines a specific neuronal mechanism for visual continuity, based on corollary discharge that is referred to as visual remapping. Both the basic characteristics of this anticipatory remapping and the factors that control it are enumerated. The last section considers hypotheses relating remapping to the perceived visual continuity across saccades, including remapping's contribution to perceived visual stability across saccades.

The superior colliculus (SC) is the most prominent visual center in mice. Studies over the past decade have greatly advanced our understanding of the function, organization, and development of the mouse SC, which has rapidly become a popular model in vision research. These studies have described the diverse and cell-type-specific visual response properties in the mouse SC, revealed their laminar and topographic organizations, and linked the mouse SC and downstream pathways with visually guided behaviors. Here, we summarize these findings, compare them with the rich literature of SC studies in other species, and highlight important gaps and exciting future directions. Given its clear importance in mouse vision and the available modern neuroscience tools, the mouse SC holds great promise for understanding the cellular, circuit, and developmental mechanisms that underlie visual processing, sensorimotor transformation, and, ultimately, behavior.

The thalamocortical pathway is the main route of communication between the eye and the cerebral cortex. During embryonic development, thalamocortical afferents travel to L4 and are sorted by receptive field position, eye of origin, and contrast polarity (i.e., preference for light or dark stimuli). In primates and carnivores, this sorting involves numerous afferents, most of which sample a limited region of the binocular field. Devoting abundant thalamocortical resources to process a limited visual field has a clear advantage: It allows many stimulus combinations to be sampled at each spatial location. Moreover, the sampling efficiency can be further enhanced by organizing the afferents in a cortical grid for eye input and contrast polarity. We argue that thalamocortical interactions within this eye–polarity grid can be used to represent multiple stimulus combinations found in nature and to build an accurate cortical map for multidimensional stimulus space.

A long-term goal of visual neuroscience is to develop and test quantitative models that account for the moment-by-moment relationship between neural responses in early visual cortex and human performance in natural visual tasks. This review focuses on efforts to address this goal by measuring and perturbing the activity of primary visual cortex (V1) neurons while nonhuman primates perform demanding, well-controlled visual tasks. We start by describing a conceptual approach—the decoder linking model (DLM) framework—in which candidate decoding models take neural responses as input and generate predicted behavior as output. The ultimate goal in this framework is to find the actual decoder—the model that best predicts behavior from neural responses. We discuss key relevant properties of primate V1 and review current literature from the DLM perspective. We conclude by discussing major technological and theoretical advances that are likely to accelerate our understanding of the link between V1 activity and behavior.

Visual information processing contains two opposite needs. There is both a need to comprehend the richness of the visual world and a need to extract only pertinent visual information to guide thoughts and behavior at a given moment. I argue that these two aspects of visual processing are mediated by two complementary visual systems in the primate brain—specifically, the occipitotemporal cortex (OTC) and the posterior parietal cortex (PPC). The role of OTC in visual processing has been documented extensively by decades of neuroscience research. I review here recent evidence from human imaging and monkey neurophysiology studies to highlight the role of PPC in adaptive visual processing. I first document the diverse array of visual representations found in PPC. I then describe the adaptive nature of visual representation in PPC by contrasting visual processing in OTC and PPC and by showing that visual representations in PPC largely originate from OTC.

Early blindness causes fundamental alterations of neural function across more than 25% of cortex—changes that span the gamut from metabolism to behavior and collectively represent one of the most dramatic examples of plasticity in the human brain. The goal of this review is to describe how the remarkable behavioral and neuroanatomical compensations demonstrated by blind individuals provide insights into the extent, mechanisms, and limits of human brain plasticity.

Receptive fields are a core property of cortical organization. Modern neuroimaging allows routine access to visual population receptive fields (pRFs), enabling investigations of clinical disorders. Yet how the underlying neural circuitry operates is controversial. The controversy surrounds observations that measurements of pRFs can change in healthy adults as well as in patients with a range of ophthalmological and neurological disorders. The debate relates to the balance between plasticity and stability of the underlying neural circuitry. We propose that to move the debate forward, the field needs to define the implied mechanism. First, we review the pRF changes in both healthy subjects and those with clinical disorders. Then, we propose a computational model that describes how pRFs can change in healthy humans. We assert that we can correctly interpret the pRF changes in clinical disorders only if we establish the capabilities and limitations of pRF dynamics in healthy humans with mechanistic models that provide quantitative predictions.

Inferior temporal cortex (IT) is a key part of the ventral visual pathway implicated in object, face, and scene perception. But how does IT work? Here, I describe an organizational scheme that marries form and function and provides a framework for future research. The scheme consists of a series of stages arranged along the posterior-anterior axis of IT, defined by anatomical connections and functional responses. Each stage comprises a complement of subregions that have a systematic spatial relationship. The organization of each stage is governed by an eccentricity template, and corresponding eccentricity representations across stages are interconnected. Foveal representations take on a role in high-acuity object vision (including face recognition); intermediate representations compute other aspects of object vision such as behavioral valence (using color and surface cues); and peripheral representations encode information about scenes. This multistage, parallel-processing model invokes an innately determined organization refined by visual experience that is consistent with principles of cortical development. The model is also consistent with principles of evolution, which suggest that visual cortex expanded through replication of retinotopic areas. Finally, the model predicts that the most extensively studied network within IT—the face patches—is not unique but rather one manifestation of a canonical set of operations that reveal general principles of how IT works.

Recognizing the people, objects, and actions in the world around us is a crucial aspect of human perception that allows us to plan and act in our environment. Remarkably, our proficiency in recognizing semantic categories from visual input is unhindered by transformations that substantially alter their appearance (e.g., changes in lighting or position). The ability to generalize across these complex transformations is a hallmark of human visual intelligence, which has been the focus of wide-ranging investigation in systems and computational neuroscience. However, while the neural machinery of human visual perception has been thoroughly described, the computational principles dictating its functioning remain unknown. Here, we review recent results in brain imaging, neurophysiology, and computational neuroscience in support of the hypothesis that the ability to support the invariant recognition of semantic entities in the visual world shapes which neural representations of sensory input are computed by human visual cortex.

The human visual system reliably extracts shape information from complex natural scenes in spite of noise and fragmentation caused by clutter and occlusions. A fast, feedforward sweep through ventral stream involving mechanisms tuned for orientation, curvature, and local Gestalt principles produces partial shape representations sufficient for simpler discriminative tasks. More complete shape representations may involve recurrent processes that integrate local and global cues. While feedforward discriminative deep neural network models currently produce the best predictions of object selectivity in higher areas of the object pathway, a generative model may be required to account for all aspects of shape perception. Research suggests that a successful model will account for our acute sensitivity to four key perceptual dimensions of shape: topology, symmetry, composition, and deformation.

Pictorial relief is a quality of visual awareness that happens when one looks into (as opposed to at) a picture. It has no physical counterpart of a geometrical nature. It takes account of cues, mentally identified in the tonal gradients of the physical picture—pigments distributed over a planar substrate. Among generally recognized qualities of relief are color, pattern, texture, shape, and depth. This review focuses on geometrical properties, the spatial variation of depth. To be aware of an extended quality like relief implies a “depth” dimension, a nonphysical spatial entity that may smoothly vary in a surface-like manner. The conceptual understanding is in terms of formal geometry. The review centers on pertinent facts and formal models. The facts are necessarily so-called brute facts (i.e., they cannot be explained scientifically). This review is a foray into the speculative and experimental phenomenology of the visual field.