From the Bench Staying on Track Vision C U R R E N T R E S E A R C H AT T H E S A L K I N S T I T U T E SPRING 2009 O Cell bodies in the developing astray. In mice genetically engineered signals, was missing. Upon closer retina sprout long, thin cables called to lack a receptor protein known as p75, investigation, the researchers found f a ll t h e s e n s e s , v i s ion i s pe r h a p s the The amount of visual axons, which extend toward visual retinal axons migrating toward their visual that the axon guidance function of most fundamental to our interactions with the world. information the optic processing centers in the brain, lured by targets in the brain docked short of their ephrin-A required that it pair up with attractive cues and making U-turns when destination, like a train halting shy of p75. Each carried out unique duties, Roughly a quarter of the brain is involved in visual processing— nerve can handle at they take the wrong path. Understanding the platform. This error was puzzling: but by working together, they provided more than nature allocates to any other sense—and references any time corresponds how they find their targets so accurately is researchers had studied p75 for the biochemical kick necessary for axons not only a central question of neuroscience decades and found it mainly associated to reach their proper brain target. This to vision also permeate our speech. roughly to the capabilities today, but is crucial to repairing defective with neuronal death and survival, but explained why retinal neurons missed of a 1 megapixel digital “Look,” we say when we’re trying to that they will be able to draw a “wiring nerve connections with the help of stem never axonal migration. the target in the mice lacking p75: camera, but we can cell therapy. The effect was reminiscent, however, They didn’t have the cellular machinery underscore a point. “I see,” we say when diagram” of the brain, a prerequisite to In a recent study, Dennis O’Leary and of defects seen when another protein, to respond to critical repellent signals nevertheless successfully we want to express understanding. Some- intervening in diseases that diminish or his team identified an unanticipated factor ephrin-A, a well-characterized sender encountered en route to the brain and navigate busy highways, one with a deep grasp of something is destroy vision. that helps keep retinal axons from going and receiver of repellent axon guidance stopped migrating prematurely. Neighborhood Watch insightful, and someone with imagination has vision. The following pages describe the approaches that Salk researchers are something even the most advanced robots cannot do. The bird enthusiast who chronicled are highly specialized and can only “see” a as TV static, to natural clips of short walks But when it comes to the actual using to uncover how one of the a flock of red-headed conures in The Wild single attribute such as color, motion, or a through a forest, and recorded the volley of sense of sight, there is a lot that we don’t most delicate and complicated Parrots of Telegraph Hill knows most of the specific luminance pattern. Growing evidence electrical spikes that resulted. When she parrots by name, proving that we can become hints that this simple picture is incomplete, applied information theory to extract mean- yet understand. What scientists do know senses allows us to navigate acutely attuned to our day-to-day environ- however, since the response of individual ing from the resulting cacophony of signals, is that we don’t “see” with our eyes; we the ever-changing world ment. While it makes perfect sense that we neurons can be strongly influenced by simple the neurons’ responses revealed that brain actually “see” with our brains. Vision around us. Location, Location, Location are best at discriminating the facial features typical of our neighbors, how our brains stimuli in the surround of the receptive field. To unveil how this phenomenon shapes cells processing visual information adjust their filtering properties to make the most begins with the formation of an image on the back of the eye, which is translated achieve this feat has been less clear. the apparent profile of neurons, Tatyana sense of incoming information, whether Much as a digital camera converts That mystery is solved in their latest study, which Neurons in the primary visual cortex only Sharpee and her collaborators presented they are taking in a walk on the beach into a cascade of nerve impulses sending light into electrical charges, the human eye found that one protein is indeed expressed in respond when a stimulus appears within the neurons specialized in recognizing luminance or trying to identify an individual conure signals deep into the brain. It is here, in turns light signals into electrical signals in the same retinal cells as the other, but it only neuron’s receptive field. But these neurons patterns with different sets of visual stimuli, within a flock of fluttering birds. the retina and sends them along the optic nerve enters the nucleus when its biological activity the brain’s visual cortex, which resides in don’t react to just anything. Instead they ranging from random noise patterns, such to the brain. Greg E. Lemke studies the signals is needed. Once its job is done, it apparently the occipital lobe at the back of the skull, that orchestrate the formation of the retina and is booted out of the nucleus into the cytoplasm, that these signals are interpreted and give the optic nerve during embryonic development. where it remains. Since for proteins—as for so Using complex gene expression techniques, many things—location is everything, Lemke’s rise to perception. This issue of From the Bench is part of a series Rebecca Newman he and his team discovered that the fate of lab is now focusing on determining how this of updates on key areas of scientific research Vice President, Development & Communications Scientists at the Salk Institute study the eye is determined by a remarkably efficient intracellular shuttling is controlled. conducted at the Salk Institute for Biological Susan Trebach different stages of visual processing to Studies. Our goal is to keep you informed of Senior Director, Communications 10010 North Torrey Pines Road system over the space of just a couple of hours. Salk researchers’ most recent findings in areas La Jolla, California 92037-1099 understand how our brains gather and Two chemical cues, or signaling proteins, must such as stem cells and regeneration, vision, Gina Kirchweger Director, Scientific Communications Post Office Box 85800 be present in the right place at the right time. plant biology, neuroscience, behavior, and more. San Diego, California 92186-5800 process meaningful information about Editor We would love to receive feedback from you While one builds the retina, the other is busy our environment. Ultimately, they would regarding this update. Sarah Lifton constructing the cord that carries visual signals Science Writer like to understand the participating to the brain. For more information, or to share your comments, Sarah Loffler please contact Judy Hodges at the Institute’s neuronal networks in such intricate detail Because these proteins aren’t supposed Print Production Coordinator Office of Development at 858.453.4100 x1882 to mingle, Lemke and his colleagues were Joe Belcovson or email firstname.lastname@example.org. surprised to find them in the same cells. Staff Photographer Studio L Graphic Design
Extrasensory Perceptions For centuries, humans have memories of associations between visual by which visual pictorial recall serves understood that there is more to visual objects, such as those between a knife to augment sensory data with “likely” perception than meets the eye. Foremost and a fork, or a train and its track. Such interpretations, in order to overcome among the factors that interact with learning, they discovered, results from the the ever-present noise, ambiguity, and incoming sensory data are our memories, strengthening of functional connections incompleteness of the retinal image. Their which enable us to infer the cause, between neurons that represent the results not only shed new light on “the category, meaning, utility, and value of associated objects. In a second set of mind’s eye,” offering an objective approach When Your retinal images. Thomas D. Albright and his team experiments, they identified neuronal events that correspond to pictorial recall to the phenomena of subjective visual imagery, dreaming, and hallucinations, but Head Spins are exploring the neuronal changes accompanying the acquisition of long-term of visual associative memories. Finally, they uncovered a specific neuronal process may change the way we think about the neuronal processing of sensory information. How, Sascha Du Lac and her team want to know, does the brain learn to stabilize “I’ll Know It an image on the retina and use eye movement to compensate for a moving head? This reflex When I Don’t See It.” Now You See It… Looking vs. Seeing needs to be fast; otherwise, our vision would According to research in the laboratory of Terrence Sejnowski, Our eyes are constantly in motion, and their As humans, we are adept at fixing field”—a window encompassing a small part attention affected them differently. One resemble an undecipherable blur. To achieve that’s more than just a twist on a common expression; it’s a concept that is lodged movements are controlled by the superior colliculus, our gaze on one object while independently of the visual field. type typically fired more frequently when the necessary speed, the connection involves deep in our brains. a brain region that has long been thought of as the directing attention to others. John Reynolds Reynolds and his team found that neurons the object in the receptive field was attended only three types of neurons: sensory neurons, When we interact with the world, two different kinds of processing lie behind our command center that allows the eyes and head to turn and his team are beginning to tease apart the typically responded more strongly when than when it was ignored. The other type which detect head movement; motor neurons, responses. Exogenous processing is the result of external stimuli—if someone enters swiftly toward or away from the sights and sounds in complex brain networks that enable humans attention was directed to the stimulus in was less influenced by attention; some fired directing eye muscles to relax or contract; and the room and we look up, for instance. Endogenous processing originates from internal our environment. Recent findings by Richard Krauzlis and other higher mammals to achieve this their receptive fields. Upon closer inspec- faster and some more slowly when attention neurons in the brainstem that link the two. contexts—perceiving a person resembles one of our relatives, for example Most of our and his team, however, have suggested that it does feat. In their latest study, animals learned to tion, however, the researchers noticed that was directed to the stimulus in the receptive Using a battery of techniques and tools experiences are some combination of the two. more than that. play a sophisticated video game that chal- different neurons produced different shaped field. This is the first study of attention they developed to manipulate molecular and Researchers in Sejnowski’s lab, developed a study to separate the endogenous They designed a series of experiments in which the lenged their visual attention-focusing skills. electrical spikes. Neurons with broad spikes ever to distinguish these two types of genetic components of specific neurons within from the exogenous. Subjects were asked to fixate on a blank screen, then told that study subjects had to track the invisible center of a visual During the game, the researchers recorded include those that transmit signals from neurons from one another. Understanding the circuitry involved, Du Lac and her team a target was hidden somewhere on the screen. When their eyes came within one target consisting of two peripheral features—much like electrical activity from individual neurons one brain area to another. Narrow-spiking the different roles they play is an essential recently identified two classes of neurons in degree of the target, they would receive a reward. Although the subjects knew only an airplane visible only by its wing lights in the night in a part of the visual cortex that has been neurons are involved in computations within step toward understanding the neural the brainstem, one superfast and the other that the locations varied, the targets were in fact clustered within a particular sky—while the researchers measured the activity of implicated in mediating visual attention. a given brain area. mechanisms that fail in neurological much slower but still faster than any neuron in area. Subjects rapidly got the hang of the distribution, without being aware of neurons in the superior colliculus. These experiments These neurons change their firing rate when After sorting the neurons into two groups diseases where attention is impaired. the cortex. Their findings, which demonstrate any underlying patterns. What the study showed is that the brain has a separate, revealed that the superior colliculus represents the a stimulus appears within their “receptive by waveform, the researchers observed that that these microcircuits are tuned for speed endogenous system that helps us sort out what is important in the world. Through location of the behaviorally relevant object (the plane's while the whole system is tuned for resilience, experience, through rewards, we learn to look for these hidden clues. These findings fuselage) rather than the visible features (the wing A Roadmap to Sight may ultimately lead to the development of may provide insights into neurological disorders such as Parkinson’s disease and lights). Understanding how the brain represents the preventive and therapeutic approaches for autism, as well as yield strategies for engaging students in the classroom. location of relevant objects may help develop better strokes, learning and movement disorders, clinical approaches to such conditions as attention Vision is the product of millions of complex computations and balance problems. deficit hyperactivity disorder and autism. that take place every second. How specific neural components contribute to these computations and give rise to visual perception, however, remains a Deciphering the Code They’ve Got Rhythm puzzle. Edward M. Callaway and his group, who are studying the organization and function of neural circuits in the visual cortex, recently have jumped a For many years, scientists tried a microscopic electrode array that records, This research is laying the technological Embedded in the inner retina, spidery cells called To get to the bottom of this paradox, Satchidananda Panda and his major hurdle to plotting the brain’s intricate “wiring diagram”: figuring out to glean information about the brain by for the very first time, the activity of more and biological groundwork for the devel- melanopsin-expressing retinal ganglion cells send signals directly team shut down all melanopsin-expressing cells, not just the gene single connections between neurons. recording the electrical activity of one than 500 nerve cells simultaneously. It opment of visual prosthetic devices that to the human circadian clock, which synchronizes the body’s for melanopsin itself, and found that the circadian clock became Using a modified rabies virus inserted into single nerve cells, they were neuron at a time. But since even the allows him to study how the retina, a thin bypass the damaged retina with the help daily rhythms with the rising and the setting of the sun. Blind completely blind to light, but normal vision was still intact. Their able to identify all the neurons to which it reaches out. Viruses that naturally simplest nervous system functions involve tissue lining the back of our eyes, conveys of tiny electrode arrays that mimic the mice without functional rods and cones—the cells responsible for experiment revealed that the melanopsin-expressing cells collect spread between neurons have previously been used to outline the flow of nerve many thousands of neurons, the activity information to the brain. By comparing the electrical signals sent to the brain in vision—can still use these melanopsin-expressing cells to adjust all the incoming information about the brightness of ambient cell communication, but without a way to stop them in their tracks, over time, of one or just a few nerve cells does not visual input with the electrical output of response to light—an advance that their biological clocks. Yet oddly enough, mice engineered to lack light—either from melanopsin and to a lesser extent from rods and they will light up the whole brain. In response, Callaway’s team pioneered a yield a full picture. In collaboration with the retina, he can reconstruct the neural could one day restore vision to people the gene that produces melanopsin, a photopigment that measures cons—and forward it to the circadian clock. Understanding how method that allows the virus to migrate only once between neighboring cells. an international group of high-energy code the retina uses to relay meaningful whose retinas have been damaged by the intensity of incoming light, continue to adjust their circadian these cells do their job may one day allow scientists to reset the While the first, published experiments were conducted using slices of mouse physicists, E. J. Chichilnisky developed information to the brain. diseases such as macular degeneration rhythms as well. body’s biological clock with a pill to alleviate symptoms associated brain, more recent studies are using live mice that allow targeting of a specific or retinitis pigmentosa. with jet lag, shifts in work schedules, seasonal changes in day class of neurons. With these tools in hand, Callaway hopes to construct the length, and disorders such as insomnia and depression. wiring map step by step.