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Early Light Refines Brain’s Circuitry for Vision
Jun 2011
PROVIDENCE, R.I., June 9, 2011 — Two new studies from Brown University on different species and using different techniques show how nascent animal brains use light to construct their central vision system.

Creatures are not born hard-wired to see. Instead, they depend on electrical activity in the retina to refine the complex circuits that process visual information. In a wide variety of nascent animals, genes provide only a rough wiring plan and then leave it to the developing nervous system to finish. Studies of mouse pups and tadpoles by Brown researchers provide new evidence of a role for exposure to light in the environment as the animals organize and refine the circuitry of their vision systems.

“Through a combination of light-independent and light-dependent processes, the visual system is getting tuned up over time,” professor of neuroscience David Berson said.

Because the retinal layer of rods and cones is not connected early in mice, neuroscientists had no reason to suspect that light helps develop neural connections for vision. David Berson, right, with Jordan Renna, has shown that photosensitive cells he discovered a decade ago are connected and do help with neural development. (Image: Mike Cohea/Brown University)

His new work, published June 5 in advance online Nature Neuroscience, offers the surprising result that light exposure can enhance how mice organize the nerve endings from their left eye and their right eye in an area of the brain where they start out somewhat jumbled. Neuroscientists had thought that mammals were unable to see at this stage, but a new type of light-sensitive cell that Berson discovered a decade ago turns out to let in the light.

Meanwhile, Berson’s colleague — assistant professor of neuroscience Carlos Aizenman — co-authored a paper published online May 31 by the Journal of Neuroscience showing that newborn tadpoles depend on light to coordinate and improve the response speed, strength and reliability of a network of neurons in a vision-processing region of their brains.

“This is how activity is allowing visual circuits to refine and sort themselves out,” Aizenman said. “Activity is fine-tuning all these connections. It’s making the circuit function in a much more efficient, synchronous way.”

Not completely blind mice
Berson and colleagues Jordan Renna and Shijun Weng conducted several experiments in newborn mice to see whether light influences the process by which the mice rewire to distinguish between their eyes.

“For certain functions, the brain wants to keep track of which eye is which,” Berson said. Among those functions are the perception of depth and distance.

At a circuit level, the brain keeps signals from the two eyes distinct by segregating their nerve endings into separate regions in the dorsal lateral geniculate nucleus (dLGN), a key way station on the path to the visual cortex and conscious visual perception. Scientists have long known this sorting-out process depends on waves of activity that spontaneously excite cells in the inner retina. They did not know until now that the waves are influenced by a light-sensitive type of cell called intrinsically photosensitive retinal ganglion cells (ipRGCs).

About a decade ago, another team led by Berson discovered the ipRGCs, which are the first light-sensitive cells to develop in the eye. These cells reside in the inner retina. The outer retina is where the more familiar rods and cones sense light. Early in life, when the brain is segregating nerve endings into distinct regions in the dLGN, the two retinal layers are not connected; until ipRGCs were discovered, there was no reason to believe that light would affect the sorting process.

The new research doesn’t say anything definitive about the consequences of light exposure at this stage for eyesight in adults, especially given that some mammals (such as monkeys) experience this developmental stage in utero.

“Whether different animals in nature are exposed to enough light to induce a change in segregation patterns is unclear,” Renna said.

But the research shows that light exposure improves how well the sorting goes, Berson said, and the work advances neuroscientists’ understanding of the eye-distinction process, which is widely studied as a model of “activity driven” neural development.

Light of the tadpoles
In his study, Aizenman collaborated with Arto Nurmikko, professor of engineering and physics, to investigate the function of the optic tectum of tadpole brains. They flooded the tectal neurons in live tadpoles with a molecule that makes calcium ions fluoresce. As whole networks of neurons became active, they’d take in the ions and glow. The researchers recorded the tadpoles with a high-resolution, high-speed camera that captured the activity of the neurons.

Carlos Aizenman and colleagues demonstrated that exposure to light was an important factor in developing cell networks in the brains of tadpoles. (Photo: David Orenstein/Brown University)

Led in the lab by lead author Heng Xu and Arseny Khakhalin, the team raised some young tadpoles under normal conditions of 12 hours of light and 12 hours of darkness during the crucial days of development when the tectum is developing. They raised others in the dark, and still others with a chemical that blocks the activity of NMDA receptors, a subtype of receptor to the neurotransmitter glutamate, which is known to promote neural rewiring.

Then they exposed all the tadpoles, however they were raised, to blue LED light flashes delivered via a fiber optic cable mounted next to the eye.

What they found over the course of several experiments was that the neural networks in the tectums of tadpoles raised under normal conditions developed a faster, more cohesive and stronger response (in terms of the number of neurons) to light.

The tectal neural networks of tadpoles kept in the dark during development failed to progress at all. Those whose NMDA receptors were blocked occupied a middle ground, showing more progress than dark-raised tadpoles but less than normal tadpoles. Tadpoles, they found, train their brains with the light they see.

Aizenman said he hopes the calcium ion imaging technique will prove useful in a wide variety of other neuroscience experiments, including studying how tadpoles neurally encode behaviors such as fleeing when they see certain stimuli.

For more information, visit:  

1. The photosensitive membrane on the inside of the human eye. 2. A scanning mechanism in optical character generation.
Americasanimal visionArseny KhakhalinArto NurmikkoBiophotonicsBrown Universitycalcium ion imagingcamerasCarlos Aizenmancentral vision systemDavid BersondLGNdorsal lateral geniculate nucleusglutamateHeng Xuimagingintrinsically photosensitive retinal ganglion cellsipRGCsJordan Rennalight exposuremiceneuroscienceNMDAResearch & TechnologyretinaShijun Wengtadpolestectumvisual circuitry organizationvisual cortexVisual Perception

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