NIH Research Matters
September 9, 2013
Brain Circuit Affects Visual Development
A mouse study revealed a circuit within the developing visual system that helps dictate how the eyes connect to the brain. The findings have implications for treating amblyopia, or lazy eye, the most common cause of visual impairment in childhood.
Neural circuits can be shaped by experience—a quality called plasticity. One example of plasticity occurs when one eye becomes dominant over the other, a condition called ocular dominance. Under normal circumstances, both eyes send signals to a brain region called the binocular zone, giving rise to depth perception. As the brain develops, the eyes compete to connect within this zone. If one eye is hindered—for example, if it’s clouded by a cataract or if the eyes are positioned at different angles—it may lose space in the binocular zone to the other eye. Over time, the brain can develop a preference for the more functional eye at the expense of the other. Amblyopia is a condition in which the brain heavily favors one eye over the other, resulting in poor depth perception.
Competition in the binocular zone takes place during a limited time called the critical period. Patching the strong eye during this period can help correct amblyopia. But once the critical period closes—around age 7 in kids—the connections are difficult to change.
A research team led by Drs. Joshua Trachtenberg at the University of California, Los Angeles, and Xiangmin Xu at the University of California, Irvine, investigated plasticity and ocular dominance in the brain at a cellular level. Their work was funded by NIH’s National Eye Institute (NEI) and the National Institute of Neurological Disorders and Stroke (NINDS). The study appeared online on August 25, 2013, in Nature.
To induce changes in ocular dominance, the scientists temporarily patched one eye in young mice. After 24 hours, they removed the patch and recorded how the firing rate of binocular zone cells changed in response to vision through each eye.
The cells’ firing rates immediately dropped by half when vision was restricted to one eye, as expected. But over the next 24 hours, the cells responding to either eye—even the eye that had been temporarily patched—increased their firing rate back to the normal range.
The team took a closer look at this increased firing rate. They tested the possibility that binocular zone cells were getting more stimulation from other parts of the brain, but that wasn’t the case. Instead, the key turned out to be a brain circuit that normally inhibits the cells. When vision through one eye was impaired, there was less inhibition from cells called parvalbumin-positive basket inhibitory neurons, or PV cells. The weakened inhibition restored the binocular zone cells’ firing rate. Further experiments showed that this restoration of normal firing is the critical first step in the induction of ocular dominance plasticity.
The scientists also found that they could manipulate PV cells to re-start plasticity in older mice that were already beyond the critical period. The researchers note that if this circuit could be controlled in the human brain—for example, with a drug or implants—it could open the door to correcting amblyopia beyond childhood.
“Our study identifies a mechanism for visual development in the young brain and shows that it’s possible to turn on the same mechanism in the adult brain, thus offering hope for treating older children and adults with amblyopia,” Trachtenberg says.
Reference: A disinhibitory microcircuit initiates critical-period plasticity in the visual cortex. Nature. 2013 Aug 25. doi: 10.1038/nature12485. [Epub ahead of print]. PMID: 23975100.
Funding: NIH’s National Eye Institute (NEI) and National Institute of Neurological Disorders and Stroke (NINDS).
NIH Research Matters
Bldg. 31, Rm. 5B64A, MSC 2094
Bethesda, MD 20892-2094
About NIH Research Matters
Editor: Harrison Wein, Ph.D.
Assistant Editors: Vicki Contie, Carol Torgan, Ph.D.
NIH Research Matters is a weekly update of NIH research highlights from the Office of Communications and Public Liaison, Office of the Director, National Institutes of Health.