retina

Hyperuniformity Found In Birds, Math And Physics

Seven years ago, Joe Corbo stared into the eye of a chicken and saw something astonishing. The color-sensitive cone cells that carpeted the retina (detached from the fowl, and mounted under a microscope) appeared as polka dots of five different colors and sizes. But Corbo observed that, unlike the randomly dispersed cones in human eyes, or the neat rows of cones in the eyes of many fish, the chicken’s cones had a haphazard and yet remarkably uniform distribution. The dots’ locations followed no discernible rule, and yet dots never appeared too close together or too far apart. Each of the five interspersed sets of cones, and all of them together, exhibited this same arresting mix of randomness and regularity. Corbo, who runs a biology lab at Washington University in St. Louis, was hooked.

“It’s extremely beautiful just to look at these patterns,” he said. “We were kind of captured by the beauty, and had, purely out of curiosity, the desire to understand the patterns better.” He and his collaborators also hoped to figure out the patterns’ function, and how they were generated. He didn’t know then that these same questions were being asked in numerous other contexts, or that he had found the first biological manifestation of a type of hidden order that has also turned up all over mathematics and physics.

From retina to cortex: An unexpected division of labor

Neurons in our brain do a remarkable job of translating sensory information into reliable representations of our world that are critical to effectively guide our behavior. The parts of the brain that are responsible for vision have long been center stage for scientists’ efforts to understand the rules that neural circuits use to encode sensory information. Years of research have led to a fairly detailed picture of the initial steps of this visual process, carried out in the retina, and how information from this stage is transmitted to the visual part of the cerebral cortex, a thin sheet of neurons that forms the outer surface of the brain. We have also learned much about the way that neurons represent visual information in visual cortex, as well as how different this representation is from the information initially supplied by the retina. Scientists are now working to understand the set of rules—the neural blueprint— that explains how these representations of visual information in the visual cortex are constructed from the information provided by the retina. Using the latest functional imaging techniques, scientists at MPFI have recently discovered a surprisingly simple rule that explains how neural circuits combine information supplied by different types of cells in the retina to build a coherent, information-rich representation of our visual world.

Vision begins with the spatial pattern of light and dark that falls on the retinal surface. One important function performed by the neural circuits in the visual cortex is the preservation of the orderly spatial relationships of light versus dark that exist on the retinal surface. These neural circuits form an orderly map of visual space where each point on the surface of the cortex contains a column of neurons that each respond to a small region of visual space— and adjacent columns respond to adjacent regions of visual space. But these cortical circuits do more than build a map of visual space: individual neurons within these columns each respond selectively to the specific orientation of edges in their region of visual space; some neurons respond preferentially to vertical edges, some to horizontal edges, and others to angles in between. This property is also mapped in a columnar fashion where all neurons in a radial column have the same orientation preference, and adjacent columns prefer slightly different orientations.

Things would be easy if all the cortex had to do was build a map of visual space: a simple one to one mapping of points on the retinal surface to columns in the cortex would be all that was necessary. But building a map of orientation that coexists with the map of visual space is a much greater challenge. This is because the neurons of the retina do not distinguish orientation in the first step of vision. Instead, information on the orientation of edges must be constructed by neural circuits in the visual cortex. This is done using information supplied from two distinct types of retinal cells: those that respond to increases in light (ON-cells) and those that respond to decreases in light (OFF-cells). Adding to the complexity, orientation selectivity depends on having individual cortical neurons receive their ON and OFF signals from non-overlapping regions of visual space, and the spatial arrangement of these regions determines the orientation preference of the cell. Cortical neurons that prefer vertical edge orientations have ON and OFF responsive regions that are displaced horizontally in visual space, those that prefer horizontal edge orientations have their ON and OFF regions displaced vertically in visual space, and this systematic relationship holds for all other edge orientations.

So cortical circuits face a paradox: How do they take the spatial information from the retina and distort it to create an orderly map of orientation selectivity, while at the same time preserving fine retinal spatial information in order to generate an orderly map of visual space? Nature’s solution might best be called ‘divide and conquer’. By using imaging technologies that allow visualization of the ON and OFF response regions of hundreds of individual cortical neurons, Kuo-Sheng Lee and Sharon Huang in David Fitzpatrick’s lab at MPFI have discovered that fine scale retinal spatial information is preserved by the OFF response regions of cortical neurons, while the ON response regions exhibit systematic spatial displacements that are necessary to build an orderly map of edge orientation. Preserving the detailed spatial information from the retina in the OFF response regions is consistent with evidence that dark elements of natural scenes convey more fine scale information than the light elements, and that OFF retinal neurons have properties that allow them to better extract this information. In addition, Lee et al. show that this OFF-anchored cortical architecture enables emergence of an additional orderly map of absolute spatial phase—a property that hasn’t received much attention from neuroscientists, but computer vision research has shown contains a wealth of information about the visual scene that can be used to efficiently encode spatial patterns, motion, and depth.

While these are important new insights into how visual information is transformed from retina to cortical representations, they pose a host of new questions about the network of synaptic connections that performs this transformation, and the developmental mechanisms that construct it, questions that the Fitzpatrick Lab continues to explore.

Retinal changes may serve as measures of brain pathology in schizophrenia

Schizophrenia is associated with structural and functional alterations of the visual system, including specific structural changes in the eye. Tracking such changes may provide new measures of risk for, and progression of the disease, according to a literature review published online in the journal Schizophrenia Research: Cognition, authored by researchers at New York Eye and Ear Infirmary of Mount Sinai and Rutgers University.

Individuals with schizophrenia have trouble with social interactions and in recognizing what is real. Past research has suggested that, in schizophrenia, abnormalities in the way the brain processes visual information contribute to these problems by making it harder to track moving objects, perceive depth, draw contrast between light and dark or different colors, organize visual elements into shapes, and  recognize facial expressions. Surprisingly though, there has been very little prior work investigating whether differences in the retina or other eye structures contribute to these disturbances.

“Our analysis of many studies suggests that measuring retinal changes may help doctors in the future to adjust schizophrenia treatment for each patient,” said study co-author Richard B. Rosen, MD, Director of Ophthalmology Research, New York Eye and Ear Infirmary of Mount Sinai, and Professor of Ophthalmology, Icahn School of Medicine at Mount Sinai. “More studies are needed to drive the understanding of the contribution of retinal and other ocular pathology to disturbances seen in these patients, and our results will help guide future research.”  

The link between vision problems and schizophrenia is well established, with as many as 62 percent of adult patients with schizophrenia experience visual distortions involving form, motion, or color. One past study found that poorer visual acuity at four years of age predicted a diagnosis of schizophrenia in adulthood, and another that children who later develop schizophrenia have elevated rates of strabismus, or misalignment of the eyes, compared to the general population.

Dr. Rosen and Steven M. Silverstein, PhD, Director of the Division of Schizophrenia Research at Rutgers University Behavioral Health Care, were the lead authors of the analysis, which examined the results of approximately 170 existing studies and grouped the findings into multiple categories, including changes in the retina vs. other parts of the eye, and changes related to dopamine vs. other neurotransmitters, key brain chemicals associated with the disease.

The newly published review found multiple, replicated, indicators of eye abnormalities in schizophrenia. One of these involves widening of small blood vessels in the eyes of schizophrenia patients, and in young people at high risk for the disorder, perhaps caused by chronic low oxygen supply to the brain. This could explain several key vision changes and serve as a marker of disease risk and worsening. Also important in this regard was thinning of the retinal nerve fiber layer in schizophrenia, which is known to be related to the onset of hallucinations and visual acuity problems in patients with Parkinson’s disease. In addition, abnormal electrical responses by retinal cells exposed to light (as measured by electroretinography) suggest cellular-level differences in the eyes of schizophrenia patients, and may represents a third useful measure of disease progression, according to the authors.  

In addition, the review highlighted the potentially detrimental effects of dopamine receptor-blocking medications on visual function in schizophrenia (secondary to their retinal effects), and the need for further research on effects of excessive retinal glutamate on visual disturbances in the disorder.  

Interestingly, the analysis found that there are no reports of people with schizophrenia who were born blind, suggesting that congenital blindness may completely or partially protect against the development of schizophrenia. Because congenitally blind people tend to have cognitive abilities in certain domains (e.g., attention) that are superior to those of healthy individuals, understanding brain re-organization after blindness may have implications for designing cognitive remediation interventions for people with schizophrenia.  

“The retina develops from the same tissue as the brain,” said Dr. Rosen. “Thus retinal changes may parallel or mirror the integrity of brain structure and function. When present in children, these changes may suggest an increased risk for schizophrenia in later life. Additional research is needed to clarify these relationships, with the goals of better predicting emergence of schizophrenia, and of predicting relapse and treatment response and people diagnosed with the condition.”  

Dr. Silverstein points out that, to date, vision has been understudied in schizophrenia, and studies of the retina and other ocular structures in the disorder are in their infancy. However, he added, “because it is much faster and less expensive to obtain data on retinal structure and function, compared to brain structure and function, measures of retinal and ocular structure and function may have an important role in both future research studies and the routine clinical care of people with schizophrenia.”

Magnetoreception molecule found in the eyes of dogs and primates

Cryptochromes are light-sensitive molecules that exist in bacteria, plants and animals. In animals, they are involved in the control of the body’s circadian rhythms. In birds, cryptochromes are also involved in the light-dependent magnetic orientation response based on the Earth’s magnetic field: cryptochrome 1a is located in photoreceptors in birds’ eyes and is activated by the magnetic field. Now researchers from the Max Planck Institute for Brain Research in Frankfurt have also detected cryptochrome 1 in photoreceptors in several mammalian species. Therefore, it is possible that these animals also have a magnetic sense that is linked to their visual system.

The perception of the Earth’s magnetic field is used by many animal species for orientation and navigation. A magnetic sense is found in some insects, fish, reptiles, birds and mammals, whereas humans do not appear to be able to perceive the Earth’s magnetic field.

The magnetic sense in migratory birds has been studied in considerable detail: unlike a boy scout’s compass, which shows the compass direction, a bird’s compass recognizes the inclination of the magnetic field lines relative to the Earth’s surface. Surprisingly, this inclination compass in birds is linked to the visual system as the magnetic field activates the light-sensitive molecule cryptochrome 1a in the retina of the bird’s eye. Cryptochrome 1a is located in the blue- to UV-sensitive cone photoreceptors and only reacts to the magnetic field if it is simultaneously excited by light.

Cryptochrome-distribution among mammals

Together with colleagues from the Ludwig-Maximilians-University Munich, the Goethe University Frankfurt, and the Universities of Duisburg-Essen and Göttingen, Christine Nießner and Leo Peichl from the Max Planck Institute for Brain Research in Frankfurt investigated the presence of cryptochrome 1 in the retinas of 90 species of mammal. Mammalian cryptochrome 1 is the equivalent of bird cryptochrome 1a. With the help of antibodies against the light-activated form of the molecule, the scientists found cryptochrome 1 only in a few species from the carnivore and primate groups. As is the case in birds, it is found in the blue-sensitive cones in these animals. The molecule is present in dog-like carnivores such as dogs, wolves, bears, foxes and badgers, but is not found in cat-like carnivores such as cats, lions and tigers. Among the primates, cryptochrome 1 is found in the orang-utan, for example. In all tested species of the other 16 mammalian orders, the researchers found no active cryptochrome 1 in the cone cells of the retina.

The active cryptochrome 1 is found in the light-sensitive outer segments of the cone cells. It is therefore unlikely that it controls the animals’ circadian rhythms from there, as this control occurs in the cell nucleus which is located a considerable distance away. It is also unlikely that cryptochrome 1 acts as an additional visual pigment for colour perception. The researchers thus suspect that some mammals may use the cryptochrome 1 to perceive the Earth’s magnetic field. In evolutionary terms, the blue cones in mammals correspond to the blue- to UV-sensitive cones in birds. It is therefore entirely possible that the cryptochrome 1 in mammals has a comparable function.

Observations of foxes, dogs and even humans actually indicate that they can perceive the Earth’s magnetic field. For example, foxes are more successful at catching mice when they pounce on them in a north-east direction. “Nevertheless, we were very surprised to find active cryptochrome 1 in the cone cells of only two mammalian groups, as species whose cones do not contain active cryptochrome 1, for example some rodents and bats, also react to the magnetic field,” says Christine Nießner.

Particle-based magnetic compass

One possible explanation for this is that animals can also perceive the magnetic field in a different way: for example, with the help of magnetite, microscopic ferrous particles in cells. A magnetite-based magnetic sense functions like a pocket compass and does not require any light. Mole rats, which live in lightless tunnel systems, orient using this kind of compass. Birds also have an additional orientation mechanism based on magnetite, which they use to determine their position.

Many fundamental questions remain open in the research on the magnetic sense. Future studies will have to reveal whether the cryptochrome 1 in the blue cones is also part of a magnetic sense in mammals or whether it fulfils other tasks in the retina.

Eye Spiral

While they may look like the delicately twisting veins of a leaf, these are veins of a different kind. They’re the blood vessels in the retina – the structure at the back of the eye packed with light-sensing cells that enable us to see. This picture was created using scanning laser ophthalmoscopy, where a fluorescent dye is injected into the bloodstream. Eventually it reaches the tiny vessels in the retina, where it glows under blue laser light. Some of the tiny vessels in the centre of this image are leaking, showing up as fuzzy bright regions against the neat network. In patients with a condition known as central serous chorioretinopathy, this leaked fluid builds up in small pools under the retina – much like a blister under the skin – causing sight problems. Techniques like this are vital for diagnosing the problem, and seeing how it respond to treatment.

Written by Kat Arney

 

You can also follow BPOD on Twitter and Facebook