In addition to the role that our visual system plays in determining what we are seeing right now, visual computations contribute in important ways to predicting what we will see next. While the role of memory in creating future predictions is often overlooked, efficient predictive computation requires the use of information about the past to estimate future events. In this article, we introduce a framework for understanding the relationship between memory and visual prediction and review the two classes of mechanisms that the visual system relies on to create future predictions. We also discuss the principles that define the mapping from predictive computations to predictive mechanisms and how downstream brain areas interpret the predictive signals computed by the visual system.
The beginning of the twenty-first century was marked by the innovative use of pharmacochemical interventions, which have since expanded to include gene-based molecular therapies. For years, treatment has focused on tackling the pathophysiology of monogenic orphan diseases, and one of the first applications of these novel genome editing technologies was the treatment of rare inherited retinal dystrophies. In this review, we present recent, ongoing, and future gene therapy-based treatment trials for choroideremia, X-linked retinitis pigmentosa, Stargardt disease, and age-related macular degeneration. As these trials pave the way toward halting the progression of such devastating diseases, we will begin to see the exciting development of newer, cutting-edge strategies including base editing and prime editing, ushering in a new era of precision medicine.
With Professor Patrick Cavanagh, I started the Harvard Vision Sciences Laboratory in 1990. Blessed with the largesse of a wealthy university, we occupied a very large common space. Here, students pursued their own projects in a uniquely cooperative and exciting scientific environment. The times were just right in the emerging and expanding field of vision science. With good thesis projects under their belt, most of the students went on to successful careers. However, my own coming of age in science did not have such a promising start. It only started well into my thirties when I joined the Smith Kettlewell Eye Research Institute in San Francisco. Providentially, it was there that I had the rare and unique opportunity to work closely and essentially only with peers (not students). Through these intense collaborations, I found my way as a scientist. Most of this account describes these formative years.
Visual processing is dynamically controlled by multiple neuromodulatory molecules that modify the responsiveness of neurons and the strength of the connections between them. In particular, modulatory control of processing in the lateral geniculate nucleus of the thalamus, V1, and V2 will alter the outcome of all subsequent processing of visual information, including the extent to and manner in which individual inputs contribute to perception and decision making and are stored in memory. This review addresses five small-molecule neuromodulators-acetylcholine, dopamine, serotonin, noradrenaline, and histamine-considering the structural basis for their action, and the effects of their release, in the early visual pathway of the macaque monkey. Traditionally, neuromodulators are studied in isolation and in discrete circuits; this review makes a case for considering the joint action of modulatory molecules and differences in modulatory effects across brain areas as a better means of understanding the diverse roles that these molecules serve.
The eye sends information about the visual world to the brain on over 20 parallel signal pathways, each specialized to signal features such as spectral reflection (color), edges, and motion of objects in the environment. Each pathway is formed by the axons of a separate type of retinal output neuron (retinal ganglion cell). In this review, we summarize what is known about the excitatory retinal inputs, brain targets, and gene expression patterns of ganglion cells in humans and nonhuman primates. We describe how most ganglion cell types receive their input from only one or two of the 11 types of cone bipolar cell and project selectively to only one or two target regions in the brain. We also highlight how genetic methods are providing tools to characterize ganglion cells and establish cross-species homologies.
The outer retina is nourished from the choroid, a capillary bed just inside the sclera. O2, glucose, and other nutrients diffuse out of the choroid and then filter through a monolayer of retinal pigment epithelium (RPE) cells to fuel the retina. Recent studies of energy metabolism have revealed striking differences between retinas and RPE cells in the ways that they extract energy from fuels. The purpose of this review is to suggest and evaluate the hypothesis that the retina and RPE have complementary metabolic roles that make them depend on each other for survival and for their abilities to perform essential and specialized functions.
Our sense of sight relies on photoreceptors, which transduce photons into the nervous system's electrochemical interpretation of the visual world. These precious photoreceptors can be disrupted by disease, injury, and aging. Once photoreceptors start to die, but before blindness occurs, the remaining retinal circuitry can withstand, mask, or exacerbate the photoreceptor deficit and potentially be receptive to newfound therapies for vision restoration. To maximize the retina's receptivity to therapy, one must understand the conditions that influence the state of the remaining retina. In this review, we provide an overview of the retina's structure and function in health and disease. We analyze a collection of observations on photoreceptor disruption and generate a predictive model to identify parameters that influence the retina's response. Finally, we speculate on whether the retina, with its remarkable capacity to function over light levels spanning nine orders of magnitude, uses these same adaptational mechanisms to withstand and perhaps mask photoreceptor loss.
The simultaneous six-pack photo lineup is a standard eyewitness identification procedure, consisting of one police suspect plus five physically similar fillers. The photo lineup is either a target-present array (the suspect is guilty) or a target-absent array (the suspect is innocent). The eyewitness is asked to search the six photos in the array with respect to a target template stored in memory (namely, the memory of the perpetrator's face). If the witness determines that the perpetrator is in fact in the lineup (detection), then the next step is to specify the position of the perpetrator's face in the lineup (localization). The witness may also determine that the perpetrator is not present and reject the lineup. In other words, a police lineup is a detection-plus-localization visual search task. Signal detection concepts that have long guided thinking about visual search have recently had a significant impact on our understanding of police lineups.
Every aspect of vision, from the opsin proteins to the eyes and the ways that they serve animal behavior, is incredibly diverse. It is only with an evolutionary perspective that this diversity can be understood and fully appreciated. In this review, I describe and explain the diversity at each level and try to convey an understanding of how the origin of the first opsin some 800 million years ago could initiate the avalanche that produced the astonishing diversity of eyes and vision that we see today. Despite the diversity, many types of photoreceptors, eyes, and visual roles have evolved multiple times independently in different animals, revealing a pattern of eye evolution strictly guided by functional constraints and driven by the evolution of gradually more demanding behaviors. I conclude the review by introducing a novel distinction between active and passive vision that points to uncharted territories in vision research.


