hubel and wiesel experiments

David H. Hubel and Torsten N. Wiesel’s Research on Optical Development in Kittens

During 1964, David Hubel and Torsten Wiesel studied the short and long term effects of depriving kittens of vision in one eye. In their experiments, Wiesel and Hubel used kittens as models for human children. Hubel and Wiesel researched whether the impairment of vision in one eye could be repaired or not and whether such impairments would impact vision later on in life. The researchers sewed one eye of a kitten shut for varying periods of time. They found that when vision impairments occurred to the kittens right after birth, their vision was significantly affected later on in life, as the cells that were responsible for processing visual information redistributed to favor the unimpaired eye. Hubel and Wiesel worked together for over twenty years and received the 1981 Nobel Prize for Physiology or Medicine for their research on the critical period for mammalian visual system development. Hubel and Wiesel’s experiments with kittens showed that there is a critical period during which the visual system develops in mammals, and it also showed that any impairment of that system during that time will affect the lifelong vision of a mammal.

In 1959, David Hubel and Torsten Wiesel met in John Hopkins Medical School in Baltimore, Maryland, where they worked in Stephen Kuffler’s neuroscience lab. That same year Kuffler and the staff of his laboratory moved to Harvard Medical School in Boston, Massachusetts. While working in Kuffler’s new lab at Harvard, Hubel and Wiesel conducted a series of experiments on cats and kittens as models for humans, and in the 1970s they repeated the experiments on primates. Their collaboration lasted for over twenty years, during which time Hubel and Wiesel elucidated details about the development of the visual system.

During the 1960s, scientists did not fully understand the development of the visual system, although Kuffler and his laboratory staff studied it closely. Researchers had yet to discover the connection between the retina, a layer of light sensitive cells on the backside of the eye, and the visual cortex of the brain. As of 2017, scientists know that the visual system consists of the eye, the optic nerve, the lateral geniculate body, and the visual cortex of the brain. The retina of the eye has rods and cones that receive visual stimuli that include colors and the forms of objects. That information is sent to the brain through the optic nerve. In the brain, the optic nerves from each eye cross at the optic chiasm, which is a cross formed by the optic nerves on the bottom of the brain. The right optic nerve becomes the left optic tract and the left optic nerve becomes the right optic tract. The optic tracts further carry the visual information into the brain and end at lateral geniculate body in the thalamus, which is a small part of the brain that serves as a relay for sensory information from the eyes to the brain. The lateral geniculate body has geniculate cells that are at a midpoint between the eye and the visual cortex. After that, the information is transferred to the visual cortex, which is the largest area of the brain that is responsible for interpreting visual information and is located on the outer backside of the brain called the occipital lobe. The visual cortex has cortical cells that are responsible for processing and interpreting visual information.

In 1964 at the time the article was published, surgeons operated on individuals with congenital cataracts, a disorder in which the lens of the eye is clouded upon birth, later in those individuals’ lives rather than at birth. Those individuals required intensive treatment after surgery, as there was still impairment to vision in the affected eye. Hubel and Wiesel questioned why their vision remained impaired. Hubel and Wiesel hypothesized that there was a time period during which the visual nerve cells develop and that if the retina did not receive any visual information at that time, the cells of the visual cortex redistribute their response in favor of the working eye. By 1964, Hubel and Wiesel performed a set of experiments to test their hypothesis. Other researchers had studied the behavior and vision of animals after they were raised in the dark, but Hubel and Wiesel were the first to study animal behavior after physically suturing one of the eyes, thus further reducing the visual input to the retina.

For the purpose of the experiment, Hubel and Wiesel used newborn kittens and sutured one of their eyes shut for the first three months of their lives. The sutured eye did not get any visual information and received 10,000 to 100,000 times less light than the normal eye. That meant that there was no visual information for the retina of the sutured eye to record and thus the visual cortex could not receive any input from that eye. Hubel and Wiesel used four kittens for the experiment.

After three months, Hubel and Wiesel opened the sutured eyes, and recorded the changes. They found a noticeable difference in cortical cell response. The researchers recorded the activity of the visual system in each kitten by inserting a tungsten electrode into the sedated kitten’s visual cortex of the brain, which let them monitor the activity of each cortical cell separately. The tungsten rod detected electrical activity or inactivity in the cortex, which indicated whether or not the visual cortex retrieved information from the previously sutured eye. By recording electrical activity in the kittens’ visual cortex, Hubel and Wiesel observed how the cells of the visual cortex reacted to different stimuli from both eyes and whether or not there was a difference in the signals from the previously sutured eye and the normal eye.

Next, Wiesel and Hubel showed the kittens different patterns of light to stimulate the cortical cells. Normally, about eighty-five percent of cortical cells respond identically to both eyes in a mammal with normal vision and only fifteen percent of those cells respond to one eye only. However, when Hubel and Wiesel performed the experiment on kittens with previously sutured eyes, they found that one out of eighty-four cells responded to the previously sutured eye and the other eighty-three cells responded to the normal eye only. That meant that the cortical cells redistributed to favor the normal eye, as it was their only source of visual information during the early development of the kitten. The researchers also noted that all kittens who had one of their eyes sutured had some cortical cells that did not respond to any stimuli at all. The researchers concluded that those cells were likely only associated with the previously sutured eye. Because those cells did not respond at all to any visual stimuli, they had not regenerated and could not be used again. That meant that some cortical neuron function can be fully lost if a vision impairment occurs during visual system development.

Hubel and Wiesel also performed a simple vision test on the kittens. They put an opaque barrier on one eye of the kitten and monitored the kitten’s movement. They later repeated the same procedure for the other eye. The researchers noted that when the kittens were allowed to see with the previously sutured eye, they were uncoordinated and showed no signs of vision. However, the normal eye functioned properly and the researchers noted no impairment. Those findings meant that the previously sutured eye had lost its vision function and was not able to recover upon being open, which provided further evidence that previous vision deprivation affects long-term vision. Hubel and Wiesel concluded that an abnormality occurred somewhere within the visual pathway from the eye to the brain that caused the cortical neurons to redistribute and function only with the normal eye.

Hubel and Wiesel investigated where in the vision pathway the abnormality of vision cells came from. They sought to know whether the abnormality was a cortical or a geniculate abnormality, as that information would reveal how the vision pathway works. Another question that they asked was whether or not depriving the kittens of light or form (sight of object) caused the abnormality in the vision pathway. Their research aimed to explain how the deprivation of either one related to the continuous vision impairment in children after surgery. Hubel and Wiesel also questioned if the kittens’ visual system reacted to the visual impairment the same way the system of an older or an adult cat would. Their findings sought to explain whether the connections made by the visual system before birth were innate or developed after birth. Finally, Hubel and Wiesel questioned whether the neural connections would deteriorate if an impairment was present, or whether the neural connections could not develop in the presence of an impairment. To answer those questions, Hubel and Wiesel performed multiple experiments with kittens and adult cats.

Following the vision tests, Hubel and Wiesel sought to answer where the abnormality occurred and how it worked. They checked the lateral geniculate body, which is a transfer site in the thalamus that receives visual information from the retina and transfers it to the occipital lobe of the brain. The cells in the lateral geniculate body normally respond more to one eye than the other. The vast majority of the geniculate cells that were associated with the previously sutured eye were intact and worked properly. However, upon analyzing those cells with a microscope, Hubel and Wiesel found that the cross sectional area of the lateral geniculate body had shrunk an average of forty percent and that some geniculate cells were smaller and contained little substance inside. That meant that the cells were not being used nearly as much as they could have been, causing the entire area to atrophy. The lateral geniculate body atrophied because it was receiving only half of its normal visual information, but it continued to transfer visual information from the eye to the brain. The researchers found no other physical abnormalities anywhere along the visual pathway. Hubel and Wiesel concluded that the abnormality that caused vision loss of the sutured eye likely occurred somewhere in the cortex of the brain, which was the last stop in the visual pathway.

Next, Hubel and Wiesel investigated whether the visual impairment in the kittens was caused by the deprivation of light or the depreciation of viewing forms. Light refers to colors as well as light or dark perception of the eye, while form refers to recognizing shapes of different objects. To determine the cause of the visual impairment, the researchers took the newborn kittens and put an opaque barrier over one of their eyes, which reduced the incoming amount of light to only ten to one hundred times. However, the barrier did not allow the kittens to distinguish forms or shapes. The results indicated that cortical cells only responded to the open eye, but the morphological changes in the lateral geniculate body cells were significantly reduced. Those findings suggested that cortical cells redistributed due to form deprivation, while the morphological abnormalities of the lateral geniculate body were due to light deprivation.

Next, Hubel and Wiesel investigated whether those visual effects would be replicated in older kittens that had already experienced vision. For that purpose, they sutured the eye of kittens shut at nine weeks of age for one month. Upon opening the eye, the researchers found that the distribution of cortical cells between eyes was still largely in favor of the open eye. However, there was almost no difference to the lateral geniculate body size. That, once again, established that the source of abnormality was cortical and not geniculate.

The researchers also tried the experiment with adult cats. They observed after visually depriving adult cats for several months, that the cats did not display any changes in cortical cell distribution or changes in the morphology of their lateral geniculate bodies. Hubel and Wiesel concluded that younger kittens were most at risk for developing cortical abnormalities and, thus, blindness. That risk declined with every month of life and was almost non-existent in adults. Hubel and Wiesel found that there was a period at the beginning of kitten’s life when the ability to view light and forms was most important for development.

Finally, Hubel and Wiesel researched whether visual pathway connections were present at birth and deteriorated with disuse or whether they did not develop if not used early on. To determine that, they experimented with three more kittens. The researchers closed the eye of one of the kittens when the kitten was eight days old, which is about the time that eyes first start to open in kittens. They closed the eyes of the other two kittens after one to two weeks of age. The researchers studied the electrical connections in the brain at birth for all three kittens and found that their cortical cells responded to visual stimuli similarly to those in adult cats. This observation meant that the cortical cells had some ocular dominance. However, the cats could recognize the stimuli from both eyes. Hubel and Wiesel studied the same electrical connections in the brain later, after reopening the sutured eyes, and found that they had deteriorated and that cortical cells had redistributed in favor of the normal eye yet again. Hubel and Wiesel concluded that the neural pathways in the visual system are present at birth and deteriorate with disuse.

Hubel and Wiesel’s experiment helped uncover how the visual system develops in mammals. First, they found a critical period during which the visual system developed and learned that the deprivation of vision during that time could impair vision forever. The conclusions of Hubel and Wiesel’s experiment led surgeons to operate on congenital cataracts as soon as the infant was diagnosed. In 1981, Hubel and Wiesel received a Nobel Prize for Physiology or Medicine for their research on the development of the visual system.

• Hubel, David H., and Torsten N. Wiesel. "Effects of monocular deprivation in kittens." Naunyn-Schmiedebergs Archiv for Experimentelle Pathologie und Pharmakologie 248 (1964): 492–7. http://hubel.med.harvard.edu/papers/HubelWiesel1964NaunynSchmiedebergsArchExpPatholPharmakol.pdf (Accessed September 10, 2017).

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• Published: 27 April 2005

Seeing sense

• Charles G. Gross 1  

Nature volume  434 ,  pages 1069–1070 ( 2005 ) Cite this article

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A look back at work that established the link between eye and brain.

Brain and Visual Perception: The Story of a 25-Year Collaboration

• David H. Hubel &
• Torsten N. Wiesel

In 1959, two postdoctoral fellows, a Canadian and a Swede working together at Johns Hopkins University, made an ‘accidental discovery’. They found that the image of an edge of a glass slide activated cells in the region of a cat's brain known as the striate cortex. Over the next 25 years, David Hubel and Torsten Wiesel expanded their observation into some of the most important developments in understanding sensory physiology, sensory psychology and the functional architecture of the cerebral cortex since E. A. Adrian initiated modern sensory neurophysiology some 75 years ago.

Hubel and Wiesel outlined a scheme for the hierarchical processing of visual information that became the frame for all subsequent work in visual neurophysiology, as well as a model for other sensory systems. They provided the first possibility of a bridge from the eye to the cognitive science of pattern recognition. Their work included the first experimental demonstration that normal experience sculpts the anatomy and physiology of the brain. They also carried out the first experimental examination of the relative role of experience and innate wiring in the development of the neural mechanisms of perception and behaviour.

Almost uniquely among basic neuroscience researchers, Hubel and Wiesel made a discovery that was immediately transferred to the clinic, in this case saving binocular vision for children born with strabismus (‘crossed’ or ‘wall’ eyes). Their experiments were so simple and elegant that they had no use for computers or elaborate apparatus, and their results were so clean that no statistics were needed. They did all this and more, essentially with their own hands and without the help of graduate students, postdocs or an army of technicians. They received a Nobel prize for their work in 1981.

The bulk of this book consists of reproductions of 28 of Hubel and Wiesel's most important papers. The book begins with autobiographical essays by both men. The rest of the book is written by Hubel, but the ‘we’ that he uses is very much a collaborative rather than a royal one.

The autobiographies are followed by several short background chapters. One, too brief and forgiving, describes the state of cortical physiology when Hubel and Wiesel began their work. The retinotopic organization of striate cortex was understood from mapping studies in cats and monkeys done by Wade Marshall and S. A. Talbot in the 1940s, but nothing was known of the response properties of individual striate-cortex neurons. Other recording studies of striate cortex at this time usually used electrical stimulation of the optic nerve, rather than discrete visual stimuli.

By the 1950s, techniques for single-neuron recording in the striate cortex had been established by groups in Montreal in Canada and Freiburg in Germany. Yet both groups usually used only diffuse illumination as the visual stimulus, and this elicited only feeble responses. Eventually the Freiburg group started using an elaborate apparatus that could move a grid across the visual field, but only in a vertical orientation, making the discovery of orientation selectivity impossible. The only responses they found were variations of the ‘on’, ‘off’ and ‘on/off’ responses described by the Nobel laureate H. Keffer Hartline some 40 years earlier.

In 1953 there were two demonstrations concerning cells in the frog's retina that could analyse complex form, one by Horace Barlow and one by Steve Kuffler, who was to become Hubel and Wiesel's postdoctoral adviser. These studies provided the starting point for Hubel and Wiesel's investigations of the cat's visual cortex in 1959, and probably sensitized the pair to the importance of the observation described in the opening of this review. Serendipity requires a prepared mind.

At about the same time, the work of Barlow and Kuffler was extended by Jerry Lettvin and Humberto Maturana in their paper ‘What the frog's eye tells the frog's brain’. Hubel and Wiesel were impressed when Lettvin showed them his complex frog neurons. The pair realized they “obviously had much in common with Lettvin and Maturana, especially our exploratory approach and freedom from complex apparatus, hypothesis, and so on. Jerry and Humberto carried their unusual approach to extremes, perhaps because they lacked an adviser like Steve who insisted we make at least a few measurements for the sake of scientific respectability.”

The remaining background chapters in this book are largely a glowing tribute to Kuffler, Hubel and Wiesel's mentor, friend and protector, who died in 1980. He brought them together at Johns Hopkins, encouraged them in every way, and took them to Harvard. Beyond this, Kuffler provided a lifelong model of doing science with your own hands, writing and rewriting over and over, and leaving your graduate students alone.

Perhaps the most interesting parts of the book are those that surround each paper or set of related papers. The forewords describe why they did each experiment. Then they describe what they did right and wrong, and comment a little (actually, very little) on subsequent developments in the field. Best of all, these parts, and the introductory chapters, are peppered with incidental remarks on how (and how not) to do science.

For example, on grants they say that much of their research “can be described as a massive fishing expedition, an expression commonly used by study sections to disparage bad grant requests”. Their research, they explain, was seldom hypothesis driven. “But the lack of a hypothesis need not necessarily prevent one from catching big fish.”

On computation: an example of the “illnesses” that can afflict science is an increase in “a theory sometimes called computation ... molecular biology, which we regard as more successful as a science than our field, seems largely to have avoided being beset with computation. In The Molecular Biology of the Gene I look in vain for equations.”

On doing experiments, they write: “Unlike much of today's science, in which the actual work is done by technicians or graduate students ... it is we who get to do the experiments.”

Hubel says he saves time by reading as little as possible in his field: “Reading most papers today is like eating sawdust.” He also says the pair benefited from their “refusal to waste time bothering with measuring intensities, rates of movement, and so on, or to spend time drawing graphs or histograms.”

On statistics: “We could hardly get excited about an effect so feeble as to require statistics for its demonstration.” And on failing to notice the directional properties of MT cells despite recording from about 200 of them: “We were lazy and not very bright.”

There are two subjects on which I would have liked to see more. The first is their students: who were they, what did they work on, and how were they mentored? Perhaps they were just left alone. There is more about how Kuffler helped the duo than how they treated their own students.

The other subject is how the two collaborators actually worked together. One disagreement is obliquely referred to without explaining what it was. They speak of bulging files of 30 years of experimental protocols, a folder for each experiment. It would have been instructive to include some examples of these protocols, even if it meant fewer reprinted papers in the volume. But perhaps those files are for the historians, rather than an autobiographical volume.

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March 1, 2014

How 1 Scientist Cracked the Brain's Visual Code

An homage to David Hubel, a Nobel Prize–winning neuroscientist

By Susana Martinez-Conde & Stephen L. Macknik

*Editor's Note - Please download PDF to view Illusions . I must admit that what most strongly motivates me ...is sheer curiosity over the workings of the most complicated structure known . —David H. Hubel (1926–2013)

In 1958 neurophysiologist David H. Hubel and his new research partner, Torsten N. Wiesel, were working like dogs to understand how cats see the world. They routinely pulled all-nighters in Stephen Kuffler's laboratory at the Wilmer Eye Institute at Johns Hopkins University. One of them would insert thin tungsten electrodes into the anesthetized cats' brains, plugging into neurons in area 17—the first region of the cortex that processes visual information. The other would use a modified ophthalmoscope fitted with glass slides to shine different patterns of light into each animal's eyes. The electrodes were connected to a machine that converted any electrical activity in the brain cells into sounds. Hubel and Wiesel listened carefully for signs of rapidly firing neurons.

For a long time they heard little of interest. Why was this so hard? They were eavesdropping on the brain's  visual  system, right?! Surely they should hear robust activity. Neurons in the retina—the light-sensitive tissue at the back of the eyes—readily responded to spots and rings of light. And neurons in the visual thalamus—the part of the brain connected directly to the retina—dutifully reacted to information relayed from the retina. So why wouldn't cortical neurons, just one level up in the visual hierarchy, also respond in kind? It was infuriating. All the more so because other scientists had warned Hubel and Wiesel that this is exactly what would happen. Again and again neurophysiologists like them had tried, and failed, to crack the visual cortex's code.

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But Hubel and Wiesel were relentless. Unraveling the workings of the cortex was critical not only to understanding vision but also to illuminating the very part of the brain that makes us human. The architecture of the cortex looks more or less the same whether you are in the frontal lobe, the auditory temporal lobe or the visual occipital lobe.

One day while conducting their usual experiments, a machine gun barrage of neural impulses surprised them both. Where did that come from? The neuron in question seemed to be teasing them, firing whenever they inserted a new glass slide onto the ophthalmoscope but then falling silent again. Something momentous was happening that they could not yet grasp. Worse, they felt they were running out of time. Often they could only record from the same neuron for just a few minutes, maybe an hour or two, before it died or slipped off the end of the electrode. Fortunately, an explanation struck them like a lightning bolt. Perhaps the neuron was not responding to the patterns of light and shadow made by the slides but rather to the edge of each new slide as it slid into the ophthalmoscope.

Exhilarated, Hubel and Wiesel continued to study the neuron as the hours ticked by. After presenting the brain cell with all kinds of visual patterns—in their previous studies they had tried everything from their own faces to pictures of glamorous female models—they finally concluded that this potentially history-changing neuron responded only to lines and edges that were oriented in specific angles. They could think of no further tests to conduct and looked at the clock. They had been studying the neuron for nine hours straight.

The primary visual cortex's secret fascination with orientation was the first of many groundbreaking discoveries that Hubel and Wiesel coaxed from the brain—for which they won the Nobel Prize in Physiology or Medicine in 1981. From this original finding, Hubel, Wiesel and others went on to discover cortical neurons that favored other specific attributes of the visual world, such as preference for specific colors, direction of motion, and even specific objects, such as hands and faces.

In memory of our dear friend and mentor, David Hubel, who died in September 2013 at the age of 87, we show some of the most beautiful and interesting perceptual implications of Hubel and Wiesel's initial breakthrough.

The Primary Visual Cortex Also known as area V1 and Brodmann area 17, the primary visual cortex is located in the brain's occipital lobe. The largest of the more than a dozen cortical areas involved in the processing of visual information, Hubel used to describe it as “the size of a credit card.”

The Science Of Orientation Selectivity Hubel and Wiesel found that whereas retinal neurons preferred dots, an otherwise quiescent cortical neuron would respond vigorously if and only if a straight line, oriented at just the right angle (say, 12 o'clock), was swept across the appropriate location on the retina. The graph shows a cortical neuron's responses (in the form of neuronal impulses, also called action potentials) to bars of different orientations. For this particular neuron, a vertically oriented bar elicited the strongest responses. From such findings, Hubel and Wiesel deduced that the higher a neuron is located in the brain's visual pathway—which stretches from the retina to the farthest regions of cortical tissue—the more complex the stimulus it responds to, for example, dots versus lines versus entire shapes. This type of hierarchy turned out to be fundamental to brain organization overall.

The Art Of Orientation Selectivity In the 19th century artists such as Georges Seurat and Camille Pissarro pioneered a new kind of painting called pointillism in which many carefully placed dots of color collectively form an image. Many decades later Norbert Krüger and Florentin Wörgötter created a type of digital art modeled on pointillism. This sunflower ( left ) is an example. Thousands of your orientation-selective visual neurons work in tandem to help your brain form a picture of the flower's contours. A close-up view ( right ) reveals how visual neurons in the cortex extract orientation information from the image. Each symbol represents the region of the image “seen” by one simulated neuron in the primary visual cortex. The color, lines and arrows in each dot represent the preferences of the activated neuron, based on Hubel and Wiesel's discoveries. The outputs of this neuronal network feed into downstream neurons that respond to increasingly complex shapes and eventually “see” the big picture—in this case, a sunflower.

Cortical Physiology in the Art Museum Lines, rectangles and other elongated solid shapes with varying orientations feature prominently in the minimalistic art of Kazimir Malevich ( left ) and Jean Tinguely ( right ). One reason these creations are so arresting, says visual neuroscientist Semir Zeki of University College London, is that they make our primary visual cortical neurons fire like crazy.

An Orientation Illusion Notice that the line gratings on the left are oblique, whereas the line gratings on the right are vertical. Stare at the short horizontal line between the gratings on the left for at least 30 seconds, then quickly move your gaze to the short line between the gratings on the right. Notice that the formerly vertical lines on the right circles now appear to lean. This occurs because different populations of visual cortical neurons are sensitive to different orientations. When your neurons look at oriented lines for a long enough time, the corresponding cortical detectors become less responsive than those that are tuned to different orientations—a process called adaptation.

*Editor's Note - Please download PDF to view Illusions .

Susana Martinez-Conde is a professor of ophthalmology, neurology, and physiology and pharmacology at SUNY Downstate Health Sciences University in Brooklyn, N.Y. She is author of the Prisma Prize–winning Sleights of Mind, along with Stephen Macknik and Sandra Blakeslee, and of Champions of Illusion, along with Stephen Macknik.

Stephen L. Macknik is a professor of opthalmology, neurology, and physiology and pharmacology at SUNY Downstate Medical Center in Brooklyn, N.Y. Along with Susana Martinez-Conde and Sandra Blakeslee, he is author of the Prisma Prize-winning Sleights of Mind . Their forthcoming book, Champions of Illusion , will be published by Scientific American/Farrar, Straus and Giroux.

Brains Explained

Dissecting the inner workings of the mind.

How Hubel and Wiesel Revolutionized Neuroscience and Made Me a Neuroscientist

As a kid, I thought biology was stupid.

Biology seemed to be taught mainly in the form of lists and diagrams. Here’s a list of the differences between prokaryotic and eukaryotic cells. There’s a diagram of the circulatory system. Here’s a list of traits specific to mammals. Then there’d be a page on the test where you’d have to label the organelles of a cell on some crappy photocopy where you could barely make out the ribosome from a Xerox smudge.

Then I learned about the brain. Maybe lists and diagrams can describe how the kidney or the heart works, but they can’t explain the brain. At least not at the level I wanted to understand it.

The brain had always seemed pretty cool , what with mediating our thoughts and emotions and all that good stuff. But in most biology classes all we learned about neuroscience were the basics: neurons, dendrites, axons, synapses. I knew that the brain was filled with cells called neurons, that different parts of a neuron send and receive signals, that neurons can communicate with each other. But what the heck did any of that have to do with thinking and feeling? How can the function of individual cells possibly be related to complex behaviors and thoughts?

The moment I decided I wanted to study the brain was the moment I got a glimpse of what bridges that gap. This bridge is called a neural circuit: a pathway of neurons that processes information into forms that are useful for making some kind of decision or response.

This moment came during an introductory biology course in college. Our professor, Robert Sapolsky, described classic experiments on the visual system performed by David Hubel and Torsten Wiesel in the 1950s and 1960s. They sought to understand how the brain takes simple information from the eyes and transforms it into our complex visual perception of the world. In 1981 they received the Nobel Prize (along with neuroscientist Roger Sperry) for their fundamental discoveries.

Hubel (left) and Wiesel (right) after receiving news of their Nobel Prize in 1981. Hubel passed away in 2013 at age 87; Wiesel, at age 90, is currently the co-director of the Mind, Brain, and Behavior Institute at Rockefeller University. (photo from PNAS ; originally from Harvard University, taken by J. Wrinn)

Light, retina, action

At its core, vision is about detecting light. You’ve probably heard of rods and cones—those are the photoreceptor cells in your eyes that physically detect photons of light. Photoreceptors are distributed across our retina, and each cell can only detect light coming from a particular point in space. To perceive an image, our brains must integrate the information from all those tiny photoreceptors.

Hubel and Wiesel didn’t know about photoreceptors back then, but previous studies had shown that the output neurons of the retina—the cells that send information from your eyes to your brain—display fairly simple responses to light. Each cell fires when you shine light in a specific small circular area of the visual field, with different cells responding to light in different places. 1 These neurons respond this way because they get positive input from photoreceptors that are clustered together in a specific area of the retina.

Additionally, these retinal output neurons are inhibited when you shine light just outside of their preferred circular areas, so they’re called “center-surround” cells. This suppression is due to inhibitory input from the corresponding photoreceptors.

Depiction of center-surround cell responses. This cell is excited by light presented in a small, circular central area (plus signs) and inhibited by light in the surrounding area (minus signs).

So basically these center-surround cells are really good at detecting little circles of light. Useful, but a long way off from recognizing the real world unless your house is full of polka dots. Hubel and Wiesel realized that a lot more visual processing must occur in the brain to allow us to see more complex things.

The retina sends visual information to the thalamus, a relay station in the brain. But the visual cells of the thalamus also have center-surround properties, suggesting that they don’t really transform the information from the retina; they mostly just pass it on. So Hubel and Wiesel decided to dive deeper into the brain.

The thalamus relays visual information to the visual cortex, a higher-order brain center. Hubel and Wiesel discovered that that’s where things really start to get interesting. 2 Their basic approach was to record the activity of neurons in cat brains while presenting various visual stimuli (i.e., patterns of light).

Circus tent science

You might think that Nobel Prize-winning research is always conducted with the utmost care and precision. Not so for Hubel and Wiesel, even by the standards of their time. The visual stimuli they showed the cats were crudely cut out of cardboard. Instead of a real projection screen, they hung a bedsheet over the pipes that ran beneath the ceiling, making the experiment room resemble a circus tent. The first time they treated a cat with formaldehyde (a toxic chemical used to preserve tissue), a mishap with the chemical bottles doused them both in a cold formaldehyde shower. “We did not relish being preserved at so young an age!” they lamented. 3

They had a frenemy named Vernon Mountcastle, an accomplished neuroscientist who had impressively recorded the activity of hundreds of cells in the brain. 4 Hubel and Wiesel later confessed, “We knew we could never catch up, so we catapulted ourselves to respectability by calling our first cell No. 3000 and numbering subsequent ones from there,” noting that “Vernon seemed suitably impressed by our series.” See, I told you these guys were geniuses.

With their makeshift experimental setup, Hubel and Wiesel started out by trying to get neurons in the visual cortex to respond to traditional visual stimuli such as dots. They had little success. No matter the size or position of the circles, their neurons just couldn’t care less. They tested more types of visual stimuli. Still no luck. In desperation, they waved their arms and jumped around, and at one point even showed pictures of beautiful women from a magazine. No response.

Then one day while they were recording from yet another stubbornly silent neuron, it suddenly started firing like crazy as they changed the projection slide that they were using to present the stimuli. Turns out, the cell was responding to the edge of the slide. That’s when Hubel and Wiesel discovered that there are cells specialized for detecting lines—a basic feature of the visual world. They recorded from that neuron for nine straight hours and then ran down the halls screaming with joy.

Visual responses in the cortex

While they feared this was some weirdo cell they’d never find again, they discovered that many neurons in cortex (which they called “simple cells”) have this property: they respond to lines presented in a specific location and orientation, such as horizontal, vertical, or something in between. Similar to center-surround cells, simple cells are inhibited by light flanking either side of their preferred linear area. 5

How might these line-sensitive simple cells arise? Well, remember that each center-surround cell in the thalamus is activated by a dot of light in a particular location. What do you get if you put a bunch of dots side by side? That’s right, a line! Hubel and Wiesel hypothesized that each simple cell might get positive input from a bunch of thalamic center-surround cells whose preferred areas are arranged in a straight line. The simple cell only fires if enough of those inputs are simultaneously active, which occurs when you shine light in a straight line of the correct orientation. A larger shape like a square won’t work: remember how center-surround cells are inhibited by light outside their preferred area, so anything wider than a thin line would trigger too much inhibition.

Model for how simple cell responses arise (from Hubel’s book, Eye, Brain, and Vision ), as described above. The simple cell receives input from multiple center-surround cells whose preferred areas (small circles with plus signs) are aligned in a straight line. The larger circles with minus signs again depict how light in the surrounding area inhibits the cells.

Hubel and Wiesel also discovered another type of cell in the visual cortex, which they called a complex cell. 6 Like simple cells, complex cells were activated by lines of a specific orientation, but many of them responded best to a line that was moving steadily through space. So now the brain can detect a totally new feature: movement.

You might guess that detecting movement is a lot more complicated than detecting stationary forms. But actually, we can propose a fairly simple model for how this property arises.

Imagine that a complex cell gets positive input from a very specific group of simple cells: cells that respond to lines with the same orientation but spanning adjacent areas of space. Activating just one of the simple cell inputs, as with a stationary line, isn’t sufficient to make the complex cell respond. But activating multiple simple cells within a small time window, as with a moving line, provides enough excitation to make the complex cell fire.

Model for how complex cell responses arise (from Hubel’s book, Eye, Brain, and Vision ), as described above. A complex cell receives input from multiple simple cells that respond to lines of the same orientation (in this case, vertical) but positioned adjacently. (Plus and minus signs depict how simple cells are excited by a line in one position but inhibited by a line in an adjacent position, similar to center-surround cells. This explains why a large shape like a square won’t activate the complex cell- it would trigger too much inhibition.)

The basics of a circuit

At this point, if you’re anything like undergrad me, your mind = blown. In just a few steps, we can explain how the visual system goes from detecting individual photons to detecting circles, lines, and movement!

Yes, we’re still far off from recognizing the vast array of visual forms that occur in the real world, but by now you can probably imagine how that occurs: by sequentially integrating information along a neural pathway to detect new features. This is essentially what all neural circuits do : they transform basic signals into useful, often sophisticated information that we can use to understand or interact with the outside world.

For me, this was a epiphany that changed the way I thought about how the brain works. The brain isn’t just a collection of neurons doing their own thing with their precious dendrites and axons; it’s a network of cells that talk to each other and trade information. It’s a community of individuals, each playing a very specific role, who work closely with each other to collectively accomplish important and amazing things. (Basically like the opposite of Congress.)

Hubel and Wiesel were two of the first to show how this might actually work—how the firing of neurons and their organization into circuits can explain our real-life experience of the world. This had a huge impact on the field of neuroscience. 7 Later studies revealed that the visual system is more complicated than they realized, but the principles they elucidated remain relevant to our modern understanding of information processing in the visual system as well as other brain circuits. Moreover, their insights undoubtedly inspired many budding neuroscientists like me to try to follow in their footsteps and probe the mysteries of the brain.

Fellow neuroscientists and neuro-enthusiasts, what inspired your interest in the brain? Leave a comment below!

1. I should mention that researchers later discovered that there are many different types of retinal output neurons, some of which show much more complicated responses than center-surround cells.

2. Again, apologies to those who study the early visual system such as the retina, which turns out to do a lot of sophisticated information processing. But Hubel and Wiesel didn’t know about that at the time.

3. The Hubel and Wiesel quotes and stories that I relate are based on these sources:

Hubel DH. Evolution of ideas on the primary visual cortex, 1955-1978: a biased historical account. Nobel Lecture, December 1981.

Hubel DH, Wiesel TN. Early exploration of the visual cortex. Neuron 20:401-412 (1998).

Gellene D. “David Hubel, Nobel-Winning Scientist, Dies at 87” . New York Times , Sept. 24, 2013.

4. Mountcastle actually just died this week at the age of 96. Like Hubel and Wiesel, his work on the visual system provided fundamental insights into how the brain works, and some believe that he should have also received the Nobel Prize.

5. Hubel DH, Wiesel TN. Receptive fields of single neurones in the cat’s striate cortex. J Physiol 148:574-591 (1959).

6. Hubel DH, Wiesel TN. Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J Physiol 160:106-154 (1962).

7. This article provides a great perspective on how Hubel and Wiesel revolutionized the field of neuroscience:

Wurtz RH. Recounting the impact of Hubel and Wiesel. J Physiol 587: 2817-2823 (2009).

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How hubel and wiesel revolutionized neuroscience and made me a neuroscientist — 3 comments.

Nice post! I was never really that excited about H&W, compared to most of my classmates and co-workers, but the way you put it really does capture the exciting power of neural circuits that they uncovered. For me, it was the mysteries of behavior and the generation of emotions that got me interested – what makes an animal fight, or flee? Where in the brain is fear or anger generated, and where is the decision to act on it made? Still led me to studying neural circuits, but through a very different path. Thanks for sharing this!

Thanks! Yeah emotions are pretty cool too :) I don’t think I learned about specific circuits underlying emotional behaviors until a lot later though, so the idea that the brain controls emotions just seemed so abstract to me, more like a question for psychologists.

Was reading “Recounting the impact of Hubel and Wiesel” by Robert H Wurtz for a school assignment when I ran into this page! Really enjoyed the “Circus Tent Science” section, science isn’t always conducted flawlessly and accidental discoveries are thus plentiful :)

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• The Nobel Prize in Physiology or Medicine 1981 - Press release
• The Nobel Prize in Physiology or Medicine 1981
• Award ceremony speech

Press release

NOBELFÖRSAMLINGEN KAROLINSKA INSTITUTET THE NOBEL ASSEMBLY AT THE KAROLINSKA INSTITUTE

9 October 1981

The Nobel Assembly of Karolinska Institutet has today decided to award the Nobel Prize in Physiology or Medicine for 1981 with one half to

Roger W. Sperry

for his discoveries concerning “the functional specialization of the cerebral hemispheres”

and the other half jointly to

David H. Hubel and Torsten N. Wiesel

for their discoveries concerning “information processing in the visual system”.

The cerebrum is made up of two halves, the hemispheres, which are structurally identical. These hemispheres are united to one another through a system consisting of millions of nerve fibers. Therefore, each hemisphere is continually informed about what is happening in the other. For more than a century we have known that, despite their similarities and close linking, the two hemispheres generally perform different functions. The left hemisphere is the center for speech and, accordingly, has been described as the dominant one and has been considered to be superior to the right hemisphere. Outside of this, little was known about where in the brain the higher functions were centered until the beginning of the 1960s when Sperry began his investigations. Sperry has brilliantly succeeded in extracting the secrets from both hemispheres and in demonstrating that they are highly specialized and also that many higher functions are centered in the right hemisphere.

Of all the sensory impressions proceeding to the brain, the visual experiences are the dominant ones. Our perception of the world around us is based essentially on the messages that reach the brain from our eyes. For a long time it was thought that the retinal image was transmitted point by point to visual centers in the brain; the cerebral cortex was a movie screen, so to speak, upon which the image in the eye was projected. Through the discoveries of Hubel and Wiesel we now know that behind the origin of the visual perception in the brain there is a considerably more complicated course of events. By following the visual impulses along their path to the various cell layers of the optical cortex, Hubel and Wiesel have been able to demonstrate that the message about the image falling on the retina undergoes a step-wise analysis in a system of nerve cells stored in columns. In this system each cell has its specific function and is responsible for a specific detail in the pattern of the retinal image.

Normally, both cerebral hemispheres are linked through the cerebral commissure, which is built up of hundreds of millions of nerve fibers. When Sperry in the beginning of the 1950s began his experimental studies on animals, the functional significance of these connections between both hemispheres was entirely unknown. In experiments on monkeys Sperry found that, if these connections were severed, each cerebral hemisphere would retain its ability to learn, but that what had been learned by one hemisphere was not accessible to the other. A neurosurgical technique, so-called commissurotomy, which was similar to what Sperry had performed on monkeys, had at that time also been carried out in a number of patients suffering from severe, intractable epilepsy. A majority of these patients showed an improvement as well as a decrease in the frequency of epileptic seizures. Otherwise, the operation entailed no obvious changes at all with regard to the patients’ general behaviour and reactions. Nor could one demonstrate with psychological test methods any impairment at all in the patients’ ability to perceive and learn. When, early in the 1960s, Sperry had the opportunity to study these patients he was able, through brilliantly designed test procedures, to show that each cerebral hemisphere in these patients had its own world of consciousness and was entirely independent of the other with regard to learning and retention. Moreover, each had its own world of perceptual experience, emotions, thoughts and memory completely out of reach of the other cerebral hemisphere.

As Sperry was able to demonstrate, the isolated left hemisphere is concerned with abstract thinking, symbolic relationships and logical analysis of details, particularly temporal relationships. It can speak, write and make mathematical calculations; in its general function it is analytical and computer-like (see figure 1). It is also the more aggressive, executive, leading hemisphere in control of the nervous system. The right hemisphere is mute and generally lacks the possibility to communicate with the outside world. It is, as Sperry expresses it, “a passive, silent passenger who leaves the driving of behaviour mainly to the left hemisphere”. Because of its muteness, the right hemisphere has so far been completely inaccessible for experimental studies, and also, as a consequence of this, has been considered as being entirely subordinate to the left hemisphere. Through his investigations, Sperry has revealed that the right hemisphere, contrary to what one previously thought, is clearly superior to the left hemisphere in many respects. This is especially true regarding the capacity for concrete thinking, spatial consciousness and comprehension of complex relationships. It is also the superior hemisphere when it comes to interpreting auditory impressions and in comprehension of music; it can better recognize melodies and better distinguish voices and intonations. In other respects, however, the right hemisphere is clearly inferior to the left. It lacks almost entirely the ability to calculate and can only perform simple additions up to 20. It completely lacks the power to subtract, multiply or divide.

Schematic illustration of the specialization of both cerebral hemispheres.

It can read and comprehend the meaning of simple, mono-syllabic nouns but cannot perceive the import of adjectives or verbs. It cannot write but is entirely superior to the left hemisphere when it comes to space perception and reproducing three-dimensional pictures (see figure 2). Almost 50 years ago the great Russian physiologist Ivan Pavlov concluded that mankind can be divided into thinkers and artists. Perhaps the left hemisphere is the dominant one in thinkers and the right hemisphere in artists.

Figure 2. The ability of both hemispheres to reproduce a picture. A patient with severed connections between both his cerebral hemispheres was asked to draw the cross and cube seen in the middle of the picture. Despite the fact that he was right-handed, he was almost entirely incapable of reproducing the pictures with his right hand (which is controlled by the left hemisphere), whereas he was able to do it relatively well with his left hand (which is controlled by his right hemisphere).

In short, with his studies on commissurotomized patients, Sperry has achieved something that was previously considered almost unattainable: He has provided us with an insight into the inner world of the brain, which hitherto had been almost completely hidden from us. With his discoveries of the specialization of both cerebral hemispheres he has given us an entirely new dimension in our comprehension of the higher functions of the brain.

At the time Hubel and Wiesel began their studies of the visual system, knowledge of the functional organization of the cerebral cortex was fragmentary. By tapping nerve-cell impulses in the various layers of the visual cortex, Hubel and Wiesel have been able to demonstrate that the message reaching the brain from the eyes undergoes an analysis in which the various components of the retinal image are interpreted with respect to their contrasts, linear patterns and the movement of the image across the retina. This analysis occurs in a rigid sequence from one nerve cell to another in which each nerve cell is responsible for a certain detail in the image pattern. To put it extremely simply, one can say that the visual cortex’s analysis of the coded message from the retina proceeds as if certain cells read the simple letters in the message and compile them into syllables that are subsequently read by other cells, which, in turn, compile the syllables into words, and these are finally read by other cells that compile words into sentences that are sent to the higher centers in the brain, where the visual impression originates and the memory of the image is stored.

Hubel and Wiesel found in their studies of the visual cortex that the cells are arranged in a regular manner in columns, and that the cells within each such column have the same functions in interpreting the impulse message from the eyes. These columns make up, in turn, so-called hypercolumns, and each such hypercolumn occupies a portion of the cerebral cortex about two-by-two millimeters in area. Within each such area the information arriving from a correspondingly small region of each eye is analyzed.

Hubel and Wiesel were also able to show by their experiments that the ability of the cells in the visual cortex to interpret the code of the impulse message from the retina is developed directly after birth. A prerequisite for this development to take place is that the eye be exposed to visual stimuli. If one eye is closed for only a few days during this period, permanent functional changes will take place in the visual cortex. Hubel and Wiesel were able to show that light stimulation in itself was insufficient to bring about normal development of the visual cortex, and that it was necessary for the retinal image to have a pattern and many contours.

This discovery illustrates, first, the brain’s high degree of plasticity immediately following birth and, second, how important it is that the brain receive a rich variety of visual stimuli during this period. It is only a slight exaggeration to say that what we see today, i.e., how we perceive the visual world around, depends on the visual experiences we had during the first stages of our lives. If the visual impressions are dull or distorted – for example, through errors in the lens system of the eye – this may lead to a permanent impairment of the ability of the brain to analyze visual impressions.

The discoveries of Hubel and Wiesel represent a break-through in research into the ability of the brain to interpret the code of the impulse message from the eyes. Thanks to their investigations we now have a deeper insight into information analysis within the visual system and into the processes forming the basis for the origin of the visual impression.

Reference Material

R.W. Sperry: Split-Brain. Approach to Learning Problems. The Neurosciences. A Study Program. 1967. pp. 714. Rockefeller University Press, N.Y.

R.W. Sperry: Lateral Specialization in the Surgically Separated Hemispheres. The Neurosciences. 3rd Study Program. 1974. pp. 5. Rockefeller University Press, N.Y.

M. Gazzaniga & J. Le Doux: The Integrated Mind. Plenum Press. 1978.

D.H. Hubel: The Brain. Scientific American 1979, vol. 241 , pp. 38.

D.H. Hubel & T.N. Wiesel: Brain Mechanisms of Vision. Scientific American 1979, vol. 241 , pp. 130.

S.W. Kuffler & J.G. Nicholls: From Neuron to the Brain. Sinauer Assoc. Inc. Publishers 1976.

D. Ottoson: Nervsystemets Fysiologi. Natur och Kultur, Stockholm, 1978.

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For one-time Hopkins researchers, accidental discovery led to Nobel Prize-winning breakthrough

Neurophysiologists wiesel, hubel receive golden goose award for their contributions to our understanding of how brain processes visual information.

By Barry Toiv

Neurophysiologists Torsten Wiesel and David Hubel, whose early research involved cats staring at black dots on a screen, are responsible for major progress in our understanding of the brain, for significant advances in the treatment of childhood cataracts, and for informing current research to enable computers to process images more like the human mind.

Image caption: Torsten Wiesel (left) and David Hubel

But their extraordinary, federally funded research really took off with a simple, fortuitous accident with the kittens in their lab: somebody pushed a glass slide too far on an overhead projector.

For their decades of research and its humble, serendipitous beginnings, Wiesel and the late Hubel have been selected as the second winners of the 2015 Golden Goose Award, the award's founders announced today. The Golden Goose Award honors researchers whose federally funded work may have seemed odd or obscure when it was first conducted but has resulted in significant benefits to society.

"Thanks to two scientists, federal funding, and a mistake in the lab, we have new discoveries about the human brain and how to improve eyesight in children," said Rep. Jim Cooper (D-TN), whose idea it was to create the Golden Goose Award. "Thank goodness for serendipity."

Cooper first had the idea for the Golden Goose Award when the late Sen. William Proxmire (D-WI) was issuing the Golden Fleece Award to target wasteful federal spending and often targeted peer-reviewed science because it sounded odd. Rep. Cooper believed such an award was needed to counter the false impression that odd-sounding research was not useful.

In the 1950s and '60s, the National Institutes of Health and the Air Force Office of Scientific Research supported the work of Hubel and Wiesel, who were studying how the visual centers in cats and monkeys process simple stimuli. Across a 20-year collaboration, beginning at the Johns Hopkins University School of Medicine and continuing at Harvard Medical School, the pair would go on to make extraordinary discoveries that eventually earned them a Nobel Prize.

The researchers had begun with what was known: light stimulates light-sensing receptor cells in the retina of the eye, and different receptor cells respond to stimuli in different parts of the retina's visual field. But Hubel and Weisel were studying nerve cells, or neurons, in higher-functioning areas of the brain not previously studied, which they found frustratingly unresponsive to their simple stimuli—small spots of light or a black dot on a clear glass slide projected onto a screen. Then, as the cats watched, one of the researchers accidentally moved the glass slide a little too far, bringing its faint edge into view. And suddenly those same neurons began firing like mad!

Over the course of the next several months, Hubel and Wiesel made the first crucial steps forward in our understanding of visual processing. They found that particular neurons in the visual cortexes of cats and monkeys—the areas in their brains responsible for processing visual information—didn't respond to simple points of light, but rather to lines, and in particular, lines and contours with specific orientations. Some neurons responded to horizontal lines, others to vertical, and still others to orientations in between. In addition, they found neurons responding to signals from both eyes, but usually one or the other would dominate.

Over subsequent years, Hubel and Wiesel refined their understanding, mapping the visual centers of their feline and primate subjects with increasing precision. They found the visual cortex consisted of narrow columns of cells organized by eye preference and response to orientation, which they termed "ocular dominance columns" and "orientation columns." Combined they formed an elegantly organized functional map of neurons that could process the complex input arriving from both of the animal's eyes.

As they were adjusting their equipment, a single line moved across the screen at a particular angle—and that caused one cat's neuron to fire. The scientists proceeded to study that single neuron for nine consecutive hours. That work led to a groundbreaking 1959 study that ultimately led to their winning the 1981 Nobel Prize in physiology or medicine, which they shared with CalTech's Roger Sperry. The Nobel committee singled out their research for solving "one of the most well-guarded secrets of the brain: the way by which its cells decode the message which the brain receives from the eye."

Hubel—who died on Sept. 22, 2013, in Lincoln, Mass., of kidney failure at 87—graduated from the McGill University School of Medicine in 1951 and came to Hopkins in 1954 after his internship and residency. He intended to study neurology but suddenly found himself drafted into the U.S. Army as a physician, assigned to the Walter Reed Army Institute of Research, Neuropsychiatry Division. There he did his first scientific research, delving into the spontaneous firing of single cortical cells in sleeping and waking cats.

He returned to Hopkins to continue his research with Vernon B. Mountcastle, already recognized as the father of neuroscience. But Mountcastle's laboratory was undergoing a lengthy renovation, so Hubel accepted an invitation from Stephen W. Kuffler to collaborate with newly arrived, Swedish-born Wiesel at the Wilmer Eye Institute. What began as a six-month research partnership lasted for the next quarter century—and was transplanted to Harvard when Kuffler transferred all nine members of his laboratory (and their families) to Massachusetts in 1959. Soon after moving from Johns Hopkins to Harvard, with their newfound understanding of the brain's organizational structure in hand, Hubel and Wiesel sought to address a perennial question in biology: nature or nurture?

Hubel and Wiesel began by studying the brains of newborn animals with no visual experience. They found that their feline and primate subjects were born with that elegant functional map already in place in their visual cortices. They found neurons that would respond only to oriented stimuli and that responded to stimulation of both eyes. They concluded that nature provides the neural connections necessary for these two basic response properties.

What then is the role of nurture for the normal development of the brain? It was known from medical clinics that children born with cataracts suffer from severe visual deficits even after their opaque lens is removed a few years after birth. With the physical blockage gone, why would this be the case? Hubel and Wiesel had shown that the necessary neural connections should be present at birth.

The researchers addressed this question by studying the impact of raising kittens and monkeys from birth with one eye covered and the other left open. They found that the animal behaved as if it was blind in the previously covered eye, just like in a child after cataract surgery. The cause of this loss of vision turned out to be that neurons in the visual cortex no longer responded to stimulation of the deprived eye but only vigorously to the normal eye. The elegant patterns of ocular dominance the researchers had seen in healthy animals disappeared, with the one dominant eye taking over almost the entire visual cortex. Over a series of experiments, they demonstrated that the brain could literally wire or rewire itself in response to external input (or lack thereof)—a phenomenon known as neuroplasticity—and that this ability seemed to fade with age.

Almost immediately, this realization of the importance of early stimulation to the wiring of the visual cortex translated from the lab to the clinic, where doctors were working to treat children born with cataracts and other eye impairments. With Hubel and Wiesel's new understanding, doctors began treating children as early as possible, with much better outcomes.

Hubel and Wiesel were pioneers of the visual system, exploring the physiology behind visual perception in animals, thereby teaching us much about how our own minds work. This is critical for today's computing technology. For some tasks, like computing and factoring large numbers, silicon has our "wetware" beat handily, but for the complex tasks like visual processing, machines are only beginning to catch up to the human brain. This is no small matter; teaching computers how our minds work is big business. The "machine vision" market is projected to grow to tens of billions of dollars in the next few years. Hubel and Wiesel's work is extremely important to this burgeoning field.

From a slip of the hand while cats watched images on a screen have come better treatments for childhood vision disorders and teaching computers how to process images—a powerful example of how science can advance society in the most unexpected ways.

Earlier this year, the Golden Goose Award founders announced that Walter Mischel, Yuichi Shoda, and Philip Peake would receive the award for their creation and development of the Marshmallow Test . A third set of honorees will be announced in September. The awardees will receive their honors on Sept. 17 at the fourth annual Golden Goose Awards ceremony, which will take place in the Jefferson Building of the Library of Congress, in Washington, DC.

Posted in Health , Science+Technology

Tagged neuroscience , vision

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• v.587(Pt 12); 2009 Jun 15

My recollections of Hubel and Wiesel and a brief review of functional circuitry in the visual pathway

The first paper of Hubel and Wiesel in The Journal of Physiology in 1959 marked the beginning of an exciting chapter in the history of visual neuroscience. Through a collaboration that lasted 25 years, Hubel and Wiesel described the main response properties of visual cortical neurons, the functional architecture of visual cortex and the role of visual experience in shaping cortical architecture. The work of Hubel and Wiesel transformed the field not only through scientific discovery but also by touching the life and scientific careers of many students. Here, I describe my personal experience as a postdoctoral student with Torsten Wiesel and how this experience influenced my own work.

I read the first papers of Hubel and Wiesel when I was an undergraduate student at the University of Santiago de Compostela, in Spain. At that time, the laboratory of my advisor, Carlos Acuña, was recording from single neurons in visual cortex and I was assigned to read a selection of the Hubel and Wiesel papers in The Journal of Physiology ( Hubel & Wiesel, 1959 , 1962 , 1963 , 1968 ). I loved reading these papers. I felt that Hubel and Wiesel had started a very exciting journey that I wanted to join. In my years as a graduate student, I found the experience of recording from visual neurons fascinating and I kept waiting for a moment when I would find an unusual stimulus that would reveal something truly amazing about the cortex. I once heard Jonathan Horton say that being naive is almost a requirement at the beginning of a scientific career. I definitely met this requirement.

Sometime in the middle of my graduate studies, I decided that I had to pursue my postdoctoral work with Hubel and Wiesel. David Hubel was the closest one to my home town. He was doing a sabbatical in Oxford and my advisor invited him to visit the laboratory. Unfortunately, he cancelled the visit at the last minute for health reasons. About a year later, Torsten Wiesel was invited to give a plenary lecture at the Spanish Society for Neuroscience and I sought this opportunity to talk to him. Finding some time to talk with Torsten turned out to be quite difficult. The meeting was small but Torsten was always very busy and continuously surrounded by senior scientists. I was assigned to take him from the room where he gave his lecture to another room and I tried to impress him with my questions as much as I could but I was not very successful. Fortunately, soon after finishing my oral presentation at the meeting, I learned from my friend Javier Cudeiro (I will always be grateful for this) that Torsten was now taking time to meet students. I waited for my turn in line and was rewarded with a full 10 minutes of his time.

Torsten Wiesel and Rockefeller University

After our brief meeting, I continued to communicate with Torsten through ‘old-fashioned’ letters that I mailed to Rockefeller University and his secretary mailed to my address in Spain. The most important letter, where he told me that I had a position in his laboratory, travelled to Santiago de Chile, went back to New York, and then travelled to Santiago de Compostela in Spain. I still keep these letters, which have become a small treasure for me. They are about one to two pages long, which is at least an order of magnitude longer than Torsten's emails nowadays! Moreover, these letters prepared me very well for what I was going to find in Rockefeller University. In one letter, Torsten told me about his new work in cortical plasticity with Charles Gilbert and, in the next one, he told me that he was becoming the University's President. In a subsequent letter, he mentioned a young fellow in his laboratory called Clay Reid. Clay wrote the next and last old-fashioned letter. The rest were phone calls and faxes. Email would come later.

I arrived in New York City with a Fulbright fellowship that paid for my salary and a great variety of social events that made my postdoctoral years really fun. Fortunately, Torsten and Clay also helped me make the postdoctoral years very productive. When I arrived, the laboratory was not ready, which made me somewhat nervous. However, we worked really hard and we started doing experiments a few weeks later. Working with Clay was a terrific experience. He was clearly very smart, always supportive and explained the most difficult concepts with amazing clarity. Torsten was now the President of Rockefeller University and did not work in the laboratory. However, we saw him frequently, particularly when we had to write an abstract or put together a talk for a scientific congress.

The meetings with Torsten are impossible to forget. Before the meeting, everybody seemed quite nervous and all the materials for display had to look perfect. Once the meeting started, Torsten basically tore down our presentations and, after he left, multiple graphs, which seemed extremely nice just a few hours before the meeting, went directly to the trash without much hesitation. The ones that survived were the very best and would become the essence of our story.

At the end of one of these meetings, Clay asked me whether I would be willing to do two overnight experiments each week instead of one. The first experiment of the week would be to continue our project and the other to start a new project with Judith Hirsch. This was the beginning of a very productive time that would generate data for many future papers.

An unusual plan and my first grant

A few years later, when Clay moved to Harvard Medical School, Torsten had to renew his grant and he revealed an unusual plan. I would become the Principal Investigator and he would become the Co-Principal Investigator in the grant. This was a terrific arrangement for me. Writing the renewal of Torsten's grant resulted in more frequent meetings that helped me in many different areas of my scientific training, and made me work harder on my poor writing skills. The grant did not do very well and had to be resubmitted, which extended my learning experience (although at that time it felt like a curse!). Currently, my main RO1 grant is still the continuation of Torsten's grant, which is now in its 22nd year.

Since now you know the unusual story of my grant, I thought I would provide you with a brief sample of what I did with it over the past years. A main theme of my laboratory has revolved around the work that I started with Torsten and Clay at Rockefeller University. I was always fascinated by the intricacies of the neuronal circuits and I thought that there was a need for a detailed study of specific connections across the visual pathway and their role in generating neuronal response properties. Clay Reid had taught me the main tools that I needed and he was always very generous at answering questions. Basically, I had to record from neurons that were monosynaptically connected or shared a monosynaptic connection and compare their response properties with techniques of automatic receptive field mapping ( Jones & Palmer, 1987 ; Reid et al. 1997 ). The monosynaptic connections had to be identified extracellularly with techniques of cross-correlation analysis, an approach that only works with fairly strong connections. Therefore, I used this method to study receptive field transformations in retinogeniculate connections, geniculocortical connections and the strong intracortical connections that link neurons from the middle layers of the cortex with neurons in the superficial layers.

Retinogeniculate connections

While working with Clay Reid at Rockefeller University, I noticed that some neighbouring geniculate cells had very similar receptive fields and often generated spikes within 1 ms of each other. This precise synchrony could be seen as a narrow peak centred at zero in the correlogram obtained after cross-correlating the firing patterns of the two geniculate cells. In some experiments, we were able to record simultaneously from a pair of synchronous geniculate cells together with the excitatory postsynaptic potential generated by one of the retinogeniculate connections, commonly know as the s-potential. These triplet recordings demonstrated that the precise 1 ms synchrony was generated by strong retinal inputs shared by the two geniculate cells. Clay Reid, Martin Usrey and I put these results together in a paper that first described this precise geniculate synchrony, showed that synchronous geniculate cells converged at the same cortical target and demonstrated that the synchronous spikes were especially effective at driving the cortical target to threshold ( Alonso et al. 1996 ).

A few years later, in my own laboratory at the University of Connecticut, I decided to initiate a large-scale comparison of the receptive field properties from synchronous geniculate cells. Two graduate students, Chun-I Yeh and Carl Stoelzel, recorded from 372 pairs of geniculate cells with overlapping receptive fields and found precise 1 ms synchrony in 88 of them. Figure 1 A illustrates one of the cell pairs that showed the strongest synchrony in our sample. The correlogram has a narrow 1 ms peak characteristic of geniculate cells sharing a retinal afferent. The receptive fields are both off-centre and have very similar position, size and response latency, although they are not identical.

A , correlogram showing a narrow 1 ms peak centred at zero (asterisk) and the receptive field centres of two geniculate cells (shown in different colours for each cell; dotted lines indicate off-responses). B , cell pairs with total receptive field overlap (100%) showed a wider range of mismatches in receptive field size than those with partial overlap. C , synchrony was more strongly modulated by stimuli in cell pairs with the most similar receptive fields. Reprinted with permission from Alonso et al. (2008) .

Subtle receptive field mismatches were commonly found in synchronous geniculate cells and were not random. When we plotted receptive field overlap against the ratio of receptive field size, all synchronous geniculate cells fell into a triangular region of the plot. Cells with complete receptive field overlap, which were more numerous, showed a wider range of receptive field mismatches in size ( Fig. 1 B ) and response latency (not shown) than those with partial receptive field overlap.

These subtle receptive field mismatches were large enough to cause stimulus-dependent changes in synchrony. Paradoxically, the most pronounced synchrony changes were found in geniculate cells with the most similar receptive fields. Geniculate cells with large receptive field mismatches showed weak 1 ms synchrony, which could not be made stronger with visual stimulation. In contrast, geniculate cells with similar receptive fields showed strong synchrony, which could be considerably reduced with appropriate stimuli. In the cells from Fig. 1 A , a bar sweeping from left to right at high speed generated two transient responses that did not overlap in time, due to the small horizontal displacement of the receptive fields. The relation between the average receptive field similarity and average synchrony modulation by stimuli could be described with a sigmoidal function, as illustrated in Fig. 1 C .

The consequences of retinogeniculate divergence can be appreciated more directly in recordings from three or four synchronous geniculate cells. Figure 2 illustrates an example from a quadruplet recording in which almost all cell combinations showed precise 1 ms synchrony. Notice that all receptive fields are of the same sign (off-centre) and are completely overlapping; however, they differ in size and temporal latency. Another graduate student in my lab, Chong Weng, noticed that receptive field size and response latency were strongly correlated in these multi-cell recordings: the larger the receptive field was, the faster the response latency ( Fig. 2 B ). This correlation between size and timing suggests that the visual information feeding the cortex improves its spatial resolution as time progresses, within a narrow window of about 10 ms ( Weng et al. 2005 ).

A , the receptive field centres are completely overlapping and are all of the same sign (off, illustrated as dotted lines). Each cell is illustrated in a different colour. B , there is a strong correlation between receptive field size and response latency. Y A : Y cell in layer A of the geniculate nucleus. X A : X cell in layer A. Reprinted with permission from Weng et al. (2005) .

The results on synchronous geniculate cells demonstrate that the retinal receptive field array is diversified at the level of the thalamus across multiple parameter dimensions including position, size and timing. This increase in receptive field diversity could be used to build cortical receptive fields more efficiently and could signal small stimulus variations to the cortex through changes in the geniculate synchrony ( Alonso et al. 2006 ). The work of Barlow, Kuffler, Hubel and Wiesel ( Barlow et al. 1957 ; Hubel, 1960 ; Wiesel, 1960 ) described the basic receptive field structure of retinal ganglion cells and geniculate cells. Now, with the aid of multielectrode arrays, we have shown how the receptive field structure of a retinal ganglion cell is diversified in space and timing through neuronal divergence at the level of the geniculate.

Geniculocortical connections

Geniculocortical connections are weaker and less temporally precise than retinogeniculate connections. And yet, they are remarkably specific. Figure 3 A shows one of the strongest geniculocortical connections that we measured at Rockefeller University ( Reid & Alonso, 1995 ; Alonso et al. 2001 ). The correlogram has a peak displaced from zero, which is smaller and wider than the peak illustrated in Fig. 1 , as would be expected from weaker and less temporally precise connections (notice the difference in time scale between Figs 1 A and ​ and3 A ). 3 A ). The receptive fields are illustrated in the inset: the on-centre receptive field from the geniculate cell is superimposed on the on-subregion from the cortical simple cell.

A , cross-correlation analysis. Correlogram and receptive fields illustrating a strong connection between a geniculate cell and a cortical simple cell. Data from Reid & Alonso (1995) and Alonso et al. (2001) . B , STCSD. This method measures the current sinks generated by single geniculate afferents in the cortex. These current sinks are strong and spatially restricted. Left, sink of a geniculate afferent restricted to cortical layer 4 (arrows mark layer limits). The sink has three components: axonal response, synaptic delay and postsynaptic response. Right, horizontal cortical distribution of the current sink (red) and the synapses from a single X geniculate axon terminal ( Humphrey et al. 1985 ). Reprinted with permission from Alonso & Swadlow (2005) and Jin et al. (2008 b ) .

A question that haunted us for many years was: how does a cortical simple cell become connected to the ‘right’ geniculate inputs? Is there a selection based on Hebbian mechanisms or is it a consequence of random wiring? Cross-correlation analysis could not be used to address this question because it was technically very difficult to measure more than a handful of geniculate inputs per cortical cell. We needed a new technique that would allow us to measure multiple, neighbouring, geniculocortical connections.

In my years at the University of Connecticut I made a terrific friend and collaborator who came up with the right tool to approach this question. Harvey Swadlow developed a method to identify multiple thalamocortical connections in a 300 μm cortical cylinder. By combining methods of spike-trigger averaging and current source density analysis (CSD), he measured for the first time the current sinks generated by a single thalamic afferent through the depths of the somatosensory cortex ( Swadlow et al. 2002 ). These current sinks turned out to be unusually strong and had a characteristic triphasic temporal profile that was a reliable marker of a single thalamocortical connection, just as a refractory period is a reliable marker of a single unit in extracellular recordings. The triphasic profile corresponded to the axon terminal response, a synaptic delay of 0.5 ms and the postsynaptic sink caused by the thalamocortical connection in the somatosensory cortex. Following Harvey's lead, we later used this method to measure the current sinks generated by single geniculocortical connections in the cat visual cortex ( Fig. 3 B ).

The current sinks measured with this method of spike-triggered CSD (or STCSD) were remarkably restricted in cortical space. They were restricted to specific layers or sublayers of the visual cortex and, horizontally, they were restricted to a region that was equivalent in size or smaller than the region covered by a geniculate axon arbor ( Fig. 3 B ).

We have recently used this technique to demonstrate that on and off geniculate afferents are segregated in cat visual cortex and that off geniculate afferents dominate the cortical representation of the area centralis. This study was led by a postdoctoral student in my lab, Jianzhong Jin, and published together with Harvey Swadlow, who developed the STCSD method, and Michael Stryker, Josh Gordon and Edward Ruthazer, who used recordings from muscimol-silenced cortex to also demonstrate the on/off segregation ( Jin et al. 2008 b ). These results provide strong support to computational models that predict a role for on/off segregation in building orientation maps in visual cortex ( Miller, 1994 ; Nakagama et al. 2000 ; Ringach, 2004 ). Moreover, the finding that off-centre geniculate afferents dominate the cortical representation of the area centralis suggest an important difference in how dark and light features are processed in visual scenes. We wonder whether our predilection to read black letters in light backgrounds (in books and visual acuity charts) has something to do with our finding. We are also working on a new paper that will provide evidence for a relation between on/off segregation and orientation preference in visual cortex and will address the question of connection specificity raised above ( Jin et al. 2008 a ).

An important prediction from Hubel and Wiesel's work is that geniculate afferents play a major role in building orientation columns in visual cortex ( Hubel & Wiesel, 1962 , 1968 ). The work that I did with Clay Reid ( Reid & Alonso, 1995 ) and, more recently with Harvey Swadlow ( Jin et al. 2008 a , b ) is heavily inspired by this prediction.

Corticocortical connections

Another discussion that I remember from my days at Rockefeller University relates to the connections between simple cells and complex cells. We were wondering why these connections had not been demonstrated with techniques of cross-correlation analysis. A common answer was that the connections were too weak to be measured. This answer was consistent with a careful study from Joseph Malpeli showing that complex cells in layers 2 + 3 of the cortex remained active when the main geniculocortical inputs to cortical area 17 were blocked and simple cells in layer 4 were silenced ( Malpeli et al. 1986 ).

I thought that Malpeli's result could be explained by the weakness of intracortical connections and the recent demonstration of rapid plasticity in the superficial layers of the cortex ( Gilbert & Wiesel, 1992 ). However, while the correlated firing generated by horizontal connections had been measured by Dan Ts’o, Charles Gilbert and Torsten Wiesel ( Ts’o et al. 1986 ), I could not find any systematic measurement of correlated firing between vertically aligned layer 4 simple cells and layer 2 + 3 complex cells. I thought that it was important to address this knowledge gap.

This reasoning led to the first experiments that I did when Clay Reid moved to Harvard Medical School and the experiments that I proposed for Torsten's grant renewal. The experiments turned out to be much more difficult than I thought and probably they would not have worked without the invaluable help of Luis Martinez, a postdoctoral student who arrived from Spain to join the lab. Figure 4 shows one of the strongest connections that we found in several years of recordings. In this example, the two cells had overlapping receptive fields, similar orientation preferences and the correlogram showed a peak displaced from zero, consistent with a monosynaptic connection ( Fig. 4 A ). This peak is wider but similar in shape to the peak from geniculocortical connections ( Fig. 3 ): it is asymmetric with respect to zero, has a fast rise time and a dip on the left side that matches the autocorrelogram of the presynaptic cell. Why do the peaks in the correlograms increase in width from retina to visual cortex (compare Figs 1 , ​ ,3 3 and ​ and4)? 4 )? In a modelling study with Francisco Vico and Francisco Veredas, we showed that the differences in peak width could be explained by differences in the time course of the excitatory postsynaptic potentials from each connection ( Veredas et al. 2005 ).

A , correlogram showing a peak consistent with a monosynaptic connection (grey line is the shuffle correlogram) and receptive fields from the complex cell (green) and simple cell (red: on-subregion; blue: off-subregion). The dotted circle is the receptive field from the multiunit activity recorded at the centre of the GABA injection in the lateral geniculate nucleus (LGN). B , a small injection of GABA in LGN blocked the activity of both the simple cell and complex cell. Reprinted with permission from Martinez & Alonso (2001) .

The experiments that I did with Luis Martinez demonstrated for first time that the connections between simple cells and complex cells could be measured with cross-correlation analysis ( Alonso & Martinez, 1998 ) and that, when a connection was demonstrated by this method, both the simple cell and the complex cell could be silenced by making a small injection of GABA in the geniculate nucleus ( Martinez & Alonso, 2001 ) ( Fig. 4 B ). These results provided strong support to a main prediction originating from the work of Hubel and Wiesel: that simple cells connect monosynaptically to complex cells and drive their visual responses ( Hubel & Wiesel, 1962 ).

Other collaborations and future directions

Most of the connections that a neuron receives are weak and cannot be studied with the techniques described above. To learn more about the functional role of these weak but numerous connections, we started studying how the behavioural state modulates neuronal response properties in awake animals. In the laboratory of Harvey Swadlow at the University of Connecticut, two postdoctoral students, Tatyana Bezdudnaya and Monica Cano, studied how changes in arousal alter the response properties of geniculate and cortical neurons in the rabbit ( Bezdudnaya et al. 2006 ; Cano et al. 2006 ). In my laboratory, currently at SUNY Optometry in New York, we are studying how changes in visual attention and task difficulty modulate neuronal responses in primary visual cortex of awake behaving primates.

Susana Martinez Conde and Steve Macknik generously provided their expertise to get the primate experiments going in my lab, by helping with the initial surgeries and with the installation of the equipment to control the behavioural task. Harvey Swadlow brought another powerful tool for these experiments. A few years ago, he developed an array of ultra-thin electrodes with independent microdrives to perform chronic recordings in awake rabbits. A main advantage of this array is that the electrodes are so thin that they can be moved through the same electrode track for months or years without causing visible tissue damage. A second advantage is that the electrodes and microdrives are very small and they are attached to the skull, providing excellent stability for single unit recording ( Swadlow et al. 2005 ).

With the help of Harvey Swadlow and his postdoctoral student, Yulia Bereshpolova, we decided to make a bold move and adapt his ultra-thin arrays for recordings in awake primates. Our boldness is beginning to pay off. We are now able to obtain high-quality single unit recordings that are exceptionally stable in awake behaving primates. The high stability of the recordings allows us to study neurons for several hours and characterize in detail their response properties. In addition, we can measure how the neuronal responses change as the monkeys perform a simple detection task that can vary in the level of difficulty and the spatial location of attention.

These experiments were led by Yao Chen, another postdoctoral student in my lab, and demonstrated the existence of two types of cells that we call difficulty-enhanced and difficulty-suppressed cells. The difficulty-enhanced cells enhance their responses at the focus of attention when the detection task becomes more difficult. In contrast, the difficulty-suppressed cells suppress their responses outside the focus of attention as difficulty increases. Interestingly, difficulty-suppressed neurons were more directionally selective ( Fig. 5 A ), had wider spikes ( Fig. 5 B ), higher contrast sensitivity ( Fig. 5 C ) and generated more transient responses (not shown) than difficulty-enhanced neurons ( Chen et al. 2008 ).

Difficulty-enhanced neurons (red circles) enhance their visual responses at the focus of attention when a detection task becomes increasingly difficult. Difficulty-suppressed neurons (blue circles) suppress their visual responses outside the focus of attention. Difficulty-suppressed neurons are more directionally selective ( A ), have wider spikes ( B ) and have higher contrast sensitivity ( C ) than difficulty-enhanced neurons. Difficulty modulation is measured by comparing the response during the hard task and the easy task. Positive and negative values indicate that the cell increased or decreased, respectively, the visual response as the task became more difficult. Reprinted with permission from Chen et al. (2008) .

The response properties of difficulty-suppressed neurons are remarkably similar to those of V1 neurons projecting to area MT ( Movshon & Newsome, 1996 ). We speculate that difficulty-suppressed neurons are part of a neuronal network that signals movement outside the focus of attention. Because peripheral movement is a powerful distracter ( Yantis, 1996 ), the reduced activity of difficulty-suppressed neurons could help to prevent moving distracters from shifting the focus of attention and compromising the success of the difficult detection task.

More recently, I started another, very productive, collaboration with Garrett Stanley, in the Department of Biomedical Engineering at Georgia Tech and Emory University. Garrett and three members of his laboratory, Nicholas Lesica, Daniel Butts and Gaëlle Desbordes have injected new, fresh ideas into my laboratory and have made computational neuroscience very accessible to all of us. Their strong background in engineering has provided a new quantitative approach that was very much needed in my lab. With Garrett, we have begun a series of studies to investigate how natural scenes are represented by single neurons and neuronal populations in early visual processing ( Lesica et al. 2007 ; Desbordes et al. 2008 ) and to study the role of temporal precision in these visual representations ( Butts et al. 2007 ). Our collaborative team is working together to connect the original, classical ideas of early visual processing inspired by the work of Hubel and Wiesel to the natural visual world, within which elemental features such as contrast, temporal and spatial frequency, and orientation vary across the scene and change with time. More recently, Michael Black from Brown University has joined the team, bringing a formal connection between biological and computer vision.

Final thoughts

When I think back about my time at Rockefeller University, I feel extremely fortunate. Torsten was not only an inspiration as a scientist but also as a leader and as a person. He also seemed to enjoy every moment, sometimes by taking unusual approaches. In an inauguration of the child-care centre at Rockefeller University, he was photographed by the University magazine when he decided to try the new slide to verify that it truly worked! I also remember the day when he showed me the new space for his lab. As we were walking towards the lab entrance, we reached a platform about four feet high that seemed to require the use of stairs. I walked towards the stairs but Torsten did something different: he used his hands to pull himself up on to the platform. After seeing him, I turned around, replicated his move and felt quite accomplished; this feeling soon vanished when I remembered that Torsten was nearly 80 years old.

Just like the jump at the entrance of the lab, Torsten continuously challenged me to stretch myself, sometimes to the point where I almost break my bones. Fortunately, my bones are still intact! It has been a real honour to meet Torsten personally and enjoy his teachings and advice during my years at Rockefeller University. I wish him and David Hubel a joyful 50th anniversary!

Acknowledgments

I would like to thank Harvey Swadlow, Garrett Stanley and Claudia Valencia for taking the time to read this manuscript and provide excellent comments. I would also like to thank NIH (NEI and NINDS) for funding the work that I presented here.

• Alonso JM, Martinez LM. Functional connectivity between simple cells and complex cells in cat striate cortex. Nat Neurosci. 1998; 1 :395–403. [ PubMed ] [ Google Scholar ]
• Alonso JM, Swadlow HA. Thalamocortical specificity and the synthesis of sensory cortical receptive fields. J Neurophysiol. 2005; 94 :26–32. [ PubMed ] [ Google Scholar ]
• Alonso JM, Usrey WM, Reid RC. Precisely correlated firing in cells of the lateral geniculate nucleus. Nature. 1996; 383 :815–819. [ PubMed ] [ Google Scholar ]
• Alonso JM, Usrey WM, Reid RC. Rules of connectivity between geniculate cells and simple cells in cat primary visual cortex. J Neurosci. 2001; 21 :4002–4015. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Alonso JM, Yeh CI, Stoelzel CR. Visual stimuli modulate precise synchronous firing within the thalamus. (Special Issue in memory of Mircea Steriade) Thalamus Relat Syst. 2008; 4 :21–34. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Alonso JM, Yeh CI, Weng C, Stoelzel C. Retinogeniculate connections: a balancing act between connection specificity and receptive field diversity. Prog Brain Res. 2006; 154 :3–13. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Barlow HB, Fitzhugh R, Kuffler SW. Dark adaptation, absolute threshold and Purkinje shift in single units of the cat's retina. J Physiol. 1957; 137 :327–337. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Bezdudnaya T, Cano M, Bereshpolova Y, Stoelzel CR, Alonso JM, Swadlow HA. Thalamic burst mode and inattention in the awake LGNd. Neuron. 2006; 49 :421–432. [ PubMed ] [ Google Scholar ]
• Butts DA, Weng C, Jin J, Yeh CI, Lesica NA, Alonso JM, Stanley GB. Temporal precision in the neural code and the timescales of natural vision. Nature. 2007; 449 :92–95. [ PubMed ] [ Google Scholar ]
• Cano M, Bezdudnaya T, Swadlow HA, Alonso JM. Brain state and contrast sensitivity in the awake visual thalamus. Nat Neurosci. 2006; 9 :1240–1242. [ PubMed ] [ Google Scholar ]
• Chen Y, Martinez-Conde S, Macknik SL, Bereshpolova Y, Swadlow HA, Alonso JM. Task difficulty modulates the activity of specific neuronal populations in primary visual cortex. Nat Neurosci. 2008; 11 :974–982. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Desbordes G, Jin J, Weng C, Lesica NA, Stanley GB, Alonso JM. Timing precision in population coding of natural scenes in the early visual system. PLoS Biol. 2008; 6 :e324. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Gilbert CD, Wiesel TN. Receptive field dynamics in adult primary visual cortex. Nature. 1992; 356 :150–152. [ PubMed ] [ Google Scholar ]
• Hubel DH. Single unit activity in lateral geniculate body and optic tract of unrestrained cats. J Physiol. 1960; 150 :91–104. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hubel DH, Wiesel TN. Receptive fields of single neurones in the cat's striate cortex. J Physiol. 1959; 148 :574–591. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hubel DH, Wiesel TN. Receptive fields, binocular interaction and functional architecture in the cat's visual cortex. J Physiol. 1962; 160 :106–154. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Hubel DH, Wiesel TN. Receptive fields of cells in striate cortex of very young, visually inexperienced kittens. J Neurophysiol. 1963; 26 :994–1002. [ PubMed ] [ Google Scholar ]
• Hubel DH, Wiesel TN. Receptive fields and functional architecture of monkey striate cortex. J Physiol. 1968; 195 :215–243. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Humphrey AL, Sur M, Uhlrich DJ, Sherman SM. Projection patterns of individual X- and Y-cell axons from the lateral geniculate nucleus to cortical area 17 in the cat. J Comp Neurol. 1985; 233 :159–189. [ PubMed ] [ Google Scholar ]
• Jin J, Wang Y, Chen Y, Swadlow HA, Alonso JM. Receptive field clustering of on and off geniculate afferents within a cortical orientation domain predicts the domain orientation preference. Abstract Viewer/Itinerary Planner, Society for Neuroscience, Washington, DC; Program No. 769.3.2008.
• Jin JZ, Weng C, Yeh CI, Gordon JA, Ruthazer ES, Stryker MP, Swadlow HA, Alonso JM. On and off domains of geniculate afferents in cat primary visual cortex. Nat Neurosci. 2008b; 11 :88–94. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Jones JP, Palmer LA. The two-dimensional spatial structure of simple receptive fields in cat striate cortex. J Neurophysiol. 1987; 58 :1187–1211. [ PubMed ] [ Google Scholar ]
• Lesica NA, Jin J, Weng C, Yeh CI, Butts DA, Stanley GB, Alonso JM. Adaptation to stimulus contrast and correlations during natural visual stimulation. Neuron. 2007; 55 :479–491. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Malpeli JG, Lee C, Schwark HD, Weyand TG. Cat area 17. I. Pattern of thalamic control of cortical layers. J Neurophysiol. 1986; 56 :1062–1073. [ PubMed ] [ Google Scholar ]
• Martinez LM, Alonso JM. Construction of complex receptive fields in cat primary visual cortex. Neuron. 2001; 32 :515–525. [ PubMed ] [ Google Scholar ]
• Miller KD. A model for the development of simple cell receptive fields and the ordered arrangement of orientation columns through activity-dependent competition between ON- and OFF-center inputs. J Neurosci. 1994; 14 :409–441. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Movshon JA, Newsome WT. Visual response properties of striate cortical neurons projecting to area MT in macaque monkeys. J Neurosci. 1996; 16 :7733–7741. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Nakagama H, Saito T, Tanaka S. Effect of imbalance in activities between ON- and OFF-center LGN cells on orientation map formation. Biol Cybern. 2000; 83 :85–92. [ PubMed ] [ Google Scholar ]
• Reid RC, Alonso JM. Specificity of monosynaptic connections from thalamus to visual cortex. Nature. 1995; 378 :281–284. [ PubMed ] [ Google Scholar ]
• Reid RC, Victor JD, Shapley RM. The use of m-sequences in the analysis of visual neurons: linear receptive field properties. Vis Neurosci. 1997; 14 :1015–1027. [ PubMed ] [ Google Scholar ]
• Ringach DL. Haphazard wiring of simple receptive fields and orientation columns in visual cortex. J Neurophysiol. 2004; 92 :468–476. [ PubMed ] [ Google Scholar ]
• Swadlow HA, Bereshpolova Y, Bezdudnaya T, Cano M, Stoelzel CR. A multi-channel, implantable microdrive system for use with sharp, ultra-fine “Reitboeck” microelectrodes. J Neurophysiol. 2005; 93 :2959–2965. [ PubMed ] [ Google Scholar ]
• Swadlow HA, Gusev AG, Bezdudnaya T. Activation of a cortical column by a thalamocortical impulse. J Neurosci. 2002; 22 :7766–7773. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Ts’o DY, Gilbert CD, Wiesel TN. Relationships between horizontal interactions and functional architecture in cat striate cortex as revealed by cross-correlation analysis. J Neurosci. 1986; 6 :1160–1170. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Veredas FJ, Vico FJ, Alonso JM. Factors determining the precision of the correlated firing generated by a monosynaptic connection in the cat visual pathway. J Physiol. 2005; 567 :1057–1078. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Weng C, Yeh CI, Stoelzel CR, Alonso JM. Receptive field size and response latency are correlated within the cat visual thalamus. J Neurophysiol. 2005; 93 :3537–3547. [ PubMed ] [ Google Scholar ]
• Wiesel TN. Receptive fields of ganglion cells in the cat's retina. J Physiol. 1960; 153 :583–594. [ PMC free article ] [ PubMed ] [ Google Scholar ]
• Yantis S. Attentional capture in vision. In: Kramer AF, Coles GH, editors. Converging Operations in the Study of Selective Attention. Washington, DC, USA: American Psychological Association; 1996. pp. 45–76. [ Google Scholar ]

In Cats David Hubel and Torsten Wiesel’s experiments showed that if a kitten is deprived of normal visual experience during a critical period at the start of its life, the circuitry of the neurons in its visual cortex is irreversibly altered.

In each of a number of newborn kittens, one eyelid was sutured shut. The kitten was allowed to grow up that way, and when it reached adulthood (around 6 months), its eyelid was opened again. Recordings were than made of the electrophysiological activity in each of the kitten’s eyes. These recordings showed an abnormally low number of neurons reacting in the eye that had been sutured shut, and an abnormally high number in the other eye. Macroscopic observation of the visual cortex showed that the ocular dominance columns for the eye that had been left open had grown larger, while those for the eye that had been closed had shrunk. Remarkably, Hubel and Wiesel also found that if the eye of an adult cat was sutured shut for a year, the responses of the cells in its visual cortex remain identical in all respects to those of a normal cat. Later experiments showed that suturing a cat’s eye shut had no effect on its visual cortex unless this visual deprivation took place during the first three months of the cat’s life. In Primates Other experiments have shown that this same phenomenon also occurs in primates, though the critical period is longer (up to age 6 months). Austin Riesen reared monkeys in darkness for the first 3 to 6 months of their lives. When these animals were then introduced into a normal environment, they had great difficulties in distinguishing even the simplest shapes. It took them weeks or even months to learn how to tell a circle from a square—a task that a normal monkey learns in a few days. Wiesel and Hubel also explored what happens in a monkey’s primary visual cortex when one of its eyelids is sutured shut for the first 6 months of its life. Normally, in monkeys, as in cats and humans, the two eyes work together to provide a single, three-dimensional image of the outside world, but this image is actually composed of two separate, slightly offset images on the two retinas. Wiesel and Hubel showed that it is not until the signals from the retinas reach the primary visual cortex that the brain begins to merge them into one, three-dimensional image. In monkeys who had one eyelid sutured shut right after birth, when the eyelid was opened again at 6 months of age, the animals had lost practically all useful vision in the eye that had been sensorily deprived. Yet recordings of electrophysiological activity in the ganglion cells of the retina of that eye, and the lateral geniculate nucleus cells for that eye, showed that these cells’ visual fields were normal and functional. It was only the primary visual cortex cells for that eye that showed practically no activity. Other experiments in which both eyelids were temporarily sutured shut showed that normal development of connectivity in the visual cortex does not depend on the absolute activity of the neural pathways from the two eyes, but rather on competition between the relative activities of these two pathways. As in other development processes for which there is a critical period, sensory deprivation does not have the same effect on adult animals—i.e., suturing shut one eyelid of an adult animal has no effect on the response of the visual cortex cells for that eye or for the other eye. In contrast, during the most sensitive part of the critical period, visual deprivation for as little as one week can have catastrophic effects on the animal’s vision for the rest of its lifetime.

In Humans In humans, certain diseases can cause a cataract (a total or partial opacity of the lens) in one or both eyes. Cataracts can occur not only in adults but also in very young children. Cataracts can now usually be removed surgically. Studies of individuals who had such surgery at various times in their lives showed that in humans as in other animals, there is a critical period for the development of the sense of sight. These studies demonstrated for the first time that early environmental influences, and hence particular neural activity patterns during a critical period, can permanently alter the neural connections in certain areas of the human brain.