Study reveals clues to brain development

October 02, 2002

Many studies have shown that sensory deprivation, such as a lack of visual stimulation soon after birth, can lead to developmental abnormalities in the brain. This is why parents are counseled to take their newborns on frequent outings to new environments, and why strollers, cribs, and bassinets are outfitted with objects sharply patterned in black and white or contrasting primary colors. Far fewer studies have investigated precisely how visual stimulation drives the formation of new neuronal structures in the brain.

Now, researchers at Cold Spring Harbor Laboratory have demonstrated that visual stimulation causes particular neurons in the brains of tadpoles to sprout new branches, and that such branching requires increased activity of some proteins (for instance, receptors for the neurotransmitter, glutamate) plus decreased activities of other proteins. The study--published this week in Nature (October 3)--provides one of the first comprehensive views of how visual stimulation guides the development of normal brain architecture.

The study focused on a region of the tadpole brain called the optic tectum, which corresponds to a structure called the superior colliculus in the brains of humans. This part of the brain coordinates visually guided movements, such as playing sports or eating a meal.

To determine how visual stimulation shapes brain architecture, the researchers engineered individual cells of the optic tectum to express a naturally fluorescent protein called Green Fluorescent Protein (GFP). GFP floats freely throughout cells, into every nook and cranny. By using time-lapse fluorescence microscopy, the scientists could observe changes in the complex three-dimensional branching patterns of optic tectal neurons, and could automatically measure such changes with the aid of a custom computer program written by one of the members of their team.

In one experiment, tadpoles were placed in a dark chamber for four hours and then moved into a chamber with a moving visual stimulus for an additional four hours. (The visual systems of frogs, humans, and many other animals--predators and prey alike--are best at detecting moving objects. Therefore, a moving visual stimulus is optimal for stimulating the cells in the frog retina.)

Time-lapse images of single optic tectal neurons were captured during both four hour periods and compared. The researchers--led by Cold Spring Harbor Laboratory neuroscientist Holly Cline--found that exposure to the moving stimulus significantly increased both the number of new branches that sprouted along the neurons as well as the length and stability of these new branches. (SEE ATTACHED FIGURE)

To determine what molecules were responsible for these light-induced changes in brain architecture, the scientists used various methods to either increase or decrease the activity of a number proteins they suspected might be involved. The results were clear: The activity of four proteins (NMDA receptors, AMPA receptors, Rac, and Cdc42) was required to trigger light-stimulated branching of optic tectal neurons. Conversely, the researchers concluded that decreased activity of two other proteins (RhoA and ROK) is required to allow light-stimulated branching of such neurons.

A description of the precise functions of these proteins is beyond the scope of this article. Nevertheless, the study suggests that by exerting opposing "grow/don't grow" influences on brain neurons, these proteins play important, coordinated roles in shaping the normal architecture of the brain, ensuring that neurons in the visual system form neither too many nor too few branches to carry out their function.

Contact information for independent researchers familiar with the study is available on request.
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Cold Spring Harbor Laboratory

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