The rising and setting of the sun is accompanied by changes in both the irradiance and the spectral distribution of the sky. Since the discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) 20 years ago, considerable progress has been made in understanding melanopsin's contributions to encoding irradiance. Much less is known about the cone inputs to ipRGCs and how they could encode changes in the color of the sky. I will summarize our recent connectomic investigation into the cone-opponent inputs to primate ipRGCs and the implications of this work on our understanding of circadian photoentrainment and the evolution of color vision.

I am working on color vision in Drosophila, identifying behaviors that involve color vision and understanding the neural circuits supporting them (Longden 2016). I have a long-term interest in understanding how neural computations operate reliably under changing circumstances, be they external changes in the sensory context, or internal changes of state such as hunger and locomotion. On internal state-modulation of sensory processing, I have shown how hunger alters visual motion processing in blowflies (Longden et al. 2014), and identified a role for octopamine in modulating motion vision during locomotion (Longden and Krapp 2009, 2010). On responses to external cues, I have shown how one kind of uncertainty in the motion of the visual scene is resolved by the fly (Saleem, Longden et al. 2012), and I have identified novel cells for processing translation-induced optic flow (Longden et al. 2017). I like working with colleagues who use different model systems, to get at principles of neural operation that might apply in many species (Ding et al. 2016, Dyakova et al. 2015). I like work motivated by computational principles - my background is computational neuroscience, with a PhD on models of memory formation in the hippocampus (Longden and Willshaw, 2007).

Simply put, the goal of my research is to describe the neuronal circuitry of the retina. The organization of the mammalian retina is certainly complex but it is not chaotic. Although there are many cell types, most adhere to a relatively constant morphology and they are distributed in non-random mosaics. Furthermore, each cell type ramifies at a characteristic depth in the retina and makes a stereotyped set of synaptic connections. In other words, these neurons form a series of local circuits across the retina. The next step is to identify the simplest and commonest of these repeating neural circuits. They are the building blocks of retinal function. If we think of it in this way, the retina is a fabulous model for the rest of the CNS. We are interested in identifying specific circuits and cell types that support the different functions of the retina. For example, there appear to be specific pathways for rod and cone mediated vision. Rods are used under low light conditions and rod circuitry is specialized for high sensitivity when photons are scarce (when you’re out camping, starlight). The hallmark of the rod-mediated system is monochromatic vision. In contrast, the cone circuits are specialized for high acuity and color vision under relatively bright or daylight conditions. Individual neurons may be filled with fluorescent dyes under visual control. This is achieved by impaling the cell with a glass microelectrode using a 3D micromanipulator. We are also interested in the diffusion of dye through coupled neuronal networks in the retina. The dye filled cells are also combined with antibody labeling to reveal neuronal connections and circuits. This triple-labeled material may be viewed and reconstructed in 3 dimensions by multi-channel confocal microscopy. We have our own confocal microscope facility in the department and timeslots are available to students in my lab.

Many animals are highly visual. They view their world through photoreceptors sensitive to different wavelengths of light. Animal survival and optimal behavioral performance may select for varying photoreceptor sensitivities depending on animal habitat or visual tasks. Our goal is to understand what drives visual diversity from both an evolutionary and molecular perspective. The group of more than 2000 cichlid fish species are an ideal system for examining such diversity. Cichlid are a colorful group of fresh water fishes. They have undergone adaptive radiation throughout Africa and the new world and occur in rivers and lakes that vary in water clarity. They are also behaviorally complex, having diverse behaviors for foraging, mate choice and even parental care. As a result, cichlids have highly diverse visual systems with cone sensitivities shifting by 30-90 nm between species. Although this group has seven cone opsin genes, individual species differ in which subset of the cone opsins they express. Some species show developmental shifts in opsin expression, switching from shorter to longer wavelength opsins through ontogeny. Other species modify that developmental program to express just one of the sets, causing the large sensitivity differences. Cichlids are therefore natural mutants for opsin expression. We have used cichlid diversity to explore the relationship between visual sensitivities and ecology. We have also exploited the genomic power of the cichlid system to identify genes and mutations that cause opsin expression shifts. Ultimately, our goal is to learn how different cichlid species see the world and whether differences matter. Behavioral experiments suggest they do indeed use color vision to survive and thrive. Cichlids therefore are a unique model for exploring how visual systems evolve in a changing world.

Among mammals, excellent color vision has evolved only in certain non-human primates. And yet, color is often assumed to be just a low-level stimulus feature with a modest role in encoding and recognizing objects. The rationale for this dogma is compelling: object recognition is excellent in grayscale images (consider black-and-white movies, where faces, places, objects, and story are readily apparent). In my talk I will discuss experiments in which we used color as a tool to uncover an organizational plan in inferior temporal cortex (parallel, multistage processing for places, faces, colors, and objects) and a visual-stimulus functional representation in prefrontal cortex (PFC). The discovery of an extensive network of color-biased domains within IT and PFC, regions implicated in high-level object vision and executive functions, compels a re-evaluation of the role of color in behavior. I will discuss behavioral studies prompted by the neurobiology that uncover a universal principle for color categorization across languages, the first systematic study of the color statistics of objects and a chromatic mechanism by which the brain may compute animacy, and a surprising paradoxical impact of memory on face color. Taken together, my talk will put forward the argument that color is not primarily for object recognition, but rather for the assessment of the likely behavioral relevance, or meaning, of the stuff we see.

We have long known that rod and cone signals interact within the retina and can even contribute to color vision, but the extent of these influences has remained unclear. New results with more powerful methods of RNA expression profiling, specific cell labeling, and single-cell recording have provided greater clarity and are showing that rod and cone signals can mix at virtually every level of signal processing. These interactions influence the integration of retinal signals and make an important contribution to visual perception.

Our study reveals the most elaborate opsin expression patterns ever described in any animal eye. In mantis shrimp, a pugnacious crustacean renowned for its visual sophistication, we found unexpected retinal expression patterns highlighting the potential for cryptic photoreceptor functional diversity, including single photoreceptors that coexpress opsins from different spectral clades and a single opsin with a putative nonvisual function important in color vision. This study demonstrates the evolutionary potential for increasing visual system functional diversity through opsin gene duplication and diversification, as well as changes in patterns of gene coexpression among photoreceptors and retinula cells. These results have significant implications for the function of other visual systems, particularly in arthropods where large numbers of retinally expressed opsins have been documented.

It has long been appreciated (and celebrated) that certain species have sensory capabilities that humans do not share, for example polarization, ultraviolet, and infrared vision. What is less appreciated however, is that our position as terrestrial human scientists can significantly affect our study of animal senses and signals, even within modalities that we do share. For example, our acute vision can lead us to over-interpret the relevance of fine patterns in animals with coarser vision, and our Cartesian heritage as scientists can lead us to divide sensory modalities into orthogonal parameters (e.g. hue and brightness for color vision), even though this division may not exist within the animal itself. This talk examines two cases from marine visual ecology where a reconsideration of our biases as sharp-eyed Cartesian land mammals can help address questions in visual ecology. The first case examines the enormous variation in visual acuity among animals with image-forming eyes, and focuses on how acknowledging the typically poorer resolving power of animals can help us interpret the function of color patterns in cleaner shrimp and their client fish. The second case examines the how the typical human division of polarized light stimuli into angle and degree of polarization is problematic, and how a physiologically relevant interpretation is both closer to the truth and resolves a number of issues, particularly when considering the propagation of polarized light

The long-term goal of my research is to study the mammalian retina as a model for the central nervous system (CNS) -- to understand how it functions in physiological conditions, how it is formed, how it breaks down in pathological conditions, and how it can be repaired. I have focused on two research themes: 1) Photoreceptor structure, synapse, circuits, and development, 2) Hibernation and metabolic adaptations in the retina and beyond. As the first neuron of the visual system, photoreceptors are vital for photoreception and transmission of visual signals. I am particularly interested in cone photoreceptors, as they mediate our daylight vision with high resolution color information. Diseases affecting cone photoreceptors compromise visual functions in the central macular area of the human retina and are thus most detrimental to our vision. However, because cones are much less abundant compared to rods in most mammals, they are less well studied. We have used the ground squirrel (GS) as a model system to study cone vision, taking advantage of their unique cone-dominant retina. In particular, we have focused on short-wavelength sensitive cones (S-cones), which are not only essential for color vision, but are also an important origin of signals for biological rhythm, mood and cognitive functions, and the growth of the eye during development. We are studying critical cone synaptic structures – synaptic ribbons, the synaptic connections of S-cones, and the development of S-cones with regard to their specific connections. These works will provide knowledge of normal retinal development and function, which can also be extended to the rest of CNS; for example, the mechanisms of synaptic targeting during development. In addition, such knowledge will benefit the development of optimal therapeutic strategies for regeneration and repair in cases of retinal degenerative disease. Many neurodegenerative diseases, including retinal diseases, are rooted in metabolic stress in neurons and/or glial cells. Using the same GS model, we aim to learn from this hibernating mammal, which possesses an amazing capability to adapt to the extreme metabolic conditions during hibernation. By exploring the mechanisms of such adaptation, we hope to discover novel therapeutic tactics for neurodegenerative diseases.