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April 7, 2017
Vol. LXIX, No. 7

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Cline Offers Insights on Visual Development

New research is revealing how visual activity guides the development of brain circuits that support vision. The findings may help researchers understand the origins of diseases such as amblyopia, when an otherwise normal eye fails to provide normal input to the brain, explained Dr. Hollis Cline, president of the Society for Neuroscience and investigator at the Scripps Research Institute, at a recent Wednesday Afternoon Lecture.

Dr. Hollis Cline
Dr. Hollis Cline

Experiments in developing animals in the 1960s and 1970s by Nobel laureates David Hubel and Torsten Wiesel showed that neurons from different eyes localize in alternating bands of tissue in the brain, where input from one or the other dominates. These so-called ocular dominance columns make the brain look striped when a tracer dye is injected into one eye and taken up by retinal ganglion cells—neurons in the back of the eye that extend their long telephone wire-like axons to visual centers of the brain. Hubel and Wiesel found that input from both eyes was necessary for development of the stripes; when they sealed one eye, the striping pattern disappeared, indicating that neurons from the seeing eye took over.

Although it was clear that sensory input from both eyes was necessary for neurons to form ocular dominance columns in the brain, how or why individual retinal ganglion cells formed the striped pattern remained unknown. To look for answers, Cline imaged developing tadpoles, whose brains are clearly visible through their skin. She found that retinal ganglion axons send out exploratory branches prior to forming synapses with other neurons. During this process, neurons that fire together in response to a common stimulus strengthen their connections and, over time, terminate their branches at the same location. She also found that neurons firing in response to the same stimulus at slightly different times terminated in slightly offset positions in the brain. In short, neurons that fire in sequence wire in sequence. The wiring rule ensures that information about retinal inputs spreads across the entire target area in the brain.

Cline’s ongoing work focuses on how incoming information from the retinal ganglion cells is processed by the brain’s inhibitory and excitatory neurons. A state of balance between these two kinds of neurons is key for processing visual information.

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