July 10, 2001 DURHAM, N.C. -- Duke University Medical Center researchers have developed evidence in animal experiments indicating that – while the brain's structures are prewired to enable development of the visual system – normal visual experience is required for complete maturation. Without such visual experience, the scientists' experiments indicated, the visual system fails to establish proper connections and is incapable of normal function.
Although the researchers caution that their findings are limited to one facet of the animals' visual system, they said they believe that a broad range of neural functions, such as motor control and the other senses might also depend on early normal experience. Such a possibility could emphasize the importance of treating a wide range of early childhood disabilities to encourage normal early experience, the scientists say.
The results of the experiments were published in the June 28 Nature by Leonard White of the medical center's division of physical therapy, David Coppola, now at Centenary College in Shreveport, La., and David Fitzpatrick of the department of neurobiology. Their work was sponsored by the National Eye Institute and was conducted in Fitzpatrick's lab in the Department of Neurobiology.
In their experiments, the researchers tested the effects of visual experience on newborn ferrets, which were chosen because they are born with their eyes shut and their visual wiring comparable to other mammals that are still in the fetal stage. Unlike other studies that have emphasized the long-term consequences of altering visual experience, White, Coppola and Fitzpatrick sought to explore the effects of experience during a brief-but-important window of brain development when the eyes open and sensory experience ensues.
The researchers' experiments aimed to explore how visual experience affected maturation of neural pathways in the animals' visual cortex that recognize lines of different orientation. The scientists studied orientation-specific structures because the activity of the brain cells that respond to such stimuli is easily and precisely measured. Furthermore, orientation selectivity must be computed by neurons in the visual cortex based on electrical signals derived from the retina -- just the sort of neural computation that might be influenced by sensory experience, the scientists said.
In the experiments, one group of such animals was reared in complete darkness, while another group was reared with their eyes kept shut. Thus, the first group had no visual experience, while the second had only undifferentiated visual stimulation of light filtering through their eyelids, but no specific experience with oriented lines.
After allowing the animals to see, the scientists imaged the visual cortices of normal animals and both groups of test animals as they were presented with images of horizontal, vertical or angled lines. They used a video imaging technique that detects minute changes in the absorption of light, which can be used to monitor the level of activity in columns of neurons in the visual cortex. These optical signals were used to assess whether orientation-selective neurons were functioning normally.
Tests of the dark-reared animals revealed appropriate activity in the brain's orientation-selective regions, but a lower degree of orientation selectivity than those of normally reared animals, the scientists said.
Most dramatic, however, were the differences between normal animals and those reared with their eyes closed. Those animals' orientation-selective regions were completely disrupted, White, Coppola and Fitzpatrick found.
"When we presented the animals with this abnormal visual experience, the visual system was doing its best to generate circuits consistent with that input, and the result was lack of orientation selectivity," said Fitzpatrick. He emphasized that the animals' orientation-related circuitry otherwise responded normally to light, lacking only orientation selectively.
Said White, "Our findings suggest that the developing visual cortex just before the eyes open is primed to receive the visual input consistent with the natural environment. So, there is a certain synergy between the intrinsic mechanisms of development and the impact of experience normally provided by the visual environment. The findings in the animals with closed eyes show that this synergy can be completely disrupted by exposure to highly abnormal visual experience." According to Fitzpatrick, the findings may offer a more balanced view of the contribution of innate wiring and experience to visual maturation.
"Historically, the thinking in this area has swung like a pendulum," Fitzpatrick said. "At one point, many people believed that experience was the key to setting up orientation, and without experience there wouldn't be much orientation selectivity. Then the pendulum swung in the other direction, with great emphasis placed on the capacity of brain to wire itself and little role for experience in the maturation of orientation selectivity. That was the situation when we began these experiments.
"So, I believe that our work serves to paint a more accurate and complete picture of the contribution of these two sources. There is an innate program capable of setting up orientation selectivity, but by itself, this program cannot achieve adult levels of orientation tuning. For that, normal visual experience is essential. The effects of abnormal experience, as in light filtered through closed lids, tell us just how powerful experience can be in altering the course of brain development. With abnormal experience, neurons in the visual cortex are far worse than if no experience of any kind had been permitted. This means that the brain is endowed genetically with certain functional abilities that can be significantly enhanced or seriously degraded depending on the quality of experience encountered in early life."
According to the scientists, further experiments are needed to understand such issues as whether there is a critical period for the maturation of orientation selectivity in development during which the animals are most sensitive to experience. Also, the scientists plan to explore whether the animals can recover normal function when given some normal experience after an initial period of abnormal experience. Importantly, said White, the scientists will also seek to understand the cellular mechanism of such visual learning.
"We present evidence in this paper that a particular type of neural connection -- the long-range horizontal connection that spans the cerebral cortex -- is disrupted in the absence of normal experience," said White. "We would like to understand the relationship between a given activity pattern in the brain and the functioning neural architecture that it produces." Such detailed studies would involve exploring the molecular mechanisms that operate at the level of the connections among neurons, said White. The scientists' findings may be relevant for understanding human visual disorders, he said.
"These results suggest that visual disabilities affecting both eyes in infants -- for example, cataracts or bandages over the eyes -- that alter patterns of neural activity in the visual centers of the brain might have an impact on the ongoing development of the visual cortex," White said. Also, he said, the results suggest a broader lesson in the importance of early experience on brain development.
"My colleagues and I who work in physical therapy are particularly interested in the implication from this work in vision that some general physical disability early in life might impact brain development," he said. "For example, one might imagine such an impact of an early musculoskeletal disability on sensory feedback patterns and neural motor control in children just learning to walk."
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