<!--intro-->Neurobiologists at Duke University Medical Center mapping the developing visual systems of newborn ferrets have discovered evidence challenging the long-held view that the brain's circuitry is largely wired by experience. Rather, they contend, much of the circuitry is inborn, with experience acting merely to preserve and enhance existing connections.<!--/intro--> The finding, published in the Nov. 17 Science, calls into question a fundamental tenet of brain development – that early sensory stimulation is critical to the basic wiring of the brain. Reporting the studies are graduate student Justin Crowley and Howard Hughes Medical Institute investigator Lawrence Katz. Besides Howard Hughes Medical Institute, their work also was supported by the National Institutes of Health. Crowley and Katz studied newborn ferrets because the animals' visual wiring is the equivalent of that of other mammals still in the fetal stage. The researchers' objective was to detect "ocular dominance columns" in a visual area of the brain called the visual cortex. The presence of these alternating stripe-like columns of nerve fibers constitutes evidence that the visual system has established a basic component of the adult visual circuit, forming groups of nerve cells in the visual cortex that respond to input from one eye or the other. The scientists used an innovative surgical technique that allowed them to inject tracer dye more precisely in order to reveal the neural connections from the eye within the cortex. They first reported use of the tracer technique to reveal ocular dominance columns in adult ferrets in a December 1999 article in Nature Neuroscience. The latest studies clearly revealed the presence of columns in the newborn animals' brains earlier than ever suspected, Katz said, and the scientists' measurements showed that in size, spacing and arrangement the columns closely resembled those previously found in adult animals. Importantly, when the researchers traced the columns in newborn ferrets that received visual information from only one eye, those animals still showed normal development of the columns. This finding confirmed that the columns did not require information from the eyes to develop normally. "For about three decades, ocular dominance columns have served as something of a Rosetta Stone for understanding how brain circuits are wired, and in particular for understanding the role of neural activity and experience in constructing them," said Katz. "The prevailing idea has been that activity is critical for establishing brain circuits. "Until now, the concept has been that neural connections in young animals were not specified very accurately, and that experience and environment were needed to refine initially crude connections, by a process of elimination, into the adult pattern," Katz said. "The critical finding in our study was that this is not the case. Rather, we found that these columns were present as early as we looked for them, and they are basically as well formed as structures in an adult. "This finding, in a way, addresses the whole question of nature versus nurture," said Katz. "It questions the notion that the young animal and its neural connections are either a ‘blank slate' or a poorly specified version of the adult's. Rather, our findings suggest that the brain of an animal or human starts life with a pretty good idea of what to expect – that it possesses an initial template of circuitry representing a ‘best-guess' of what experiences the animal will encounter. If normal experience ensues, this template is preserved and enhanced. But if the animal encounters something different during a critical period immediately after birth, there's some possibility of altering these connections." Added Crowley, "The assumption that activity was important in initially constructing these circuits was based on good data from animals on the remodeling of circuits by visual experience during the critical period. These data led investigators to believe that the influences on wiring connections during this later period were the same ones that wired them during establishment of the circuitry. It was a good guess, but not necessarily a correct one." According to Katz, the findings emphasize the importance of current scientific efforts to discover the intricate molecular cues that guide the initial wiring of the brain. "While until now many scientists had searched for the mechanism by which activity drives neuronal competition to form certain brain structures, we're now offering evidence that it may not be competition at all. Rather, neurons in developing animals may initially form connections based on molecular labels. We believe that the search for these guidance molecules is critical to understanding the initial stages of brain wiring."