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Nestled in the heart of the vertebrate brain is a center of multisensory integration and movement control called the superior colliculus. In rodents, this region of the brain integrates multisensory inputs – visual cues, sounds, tactile information, and smells – and provides output signals to a variety of motor control centers in the brain, coordinating the animal’s movements in response. to its environment.
Although the superior colliculus makes up a relatively small portion of brain volume in mice, it is a processing powerhouse, in part because it is made up of precise cell layers that organize and refine signaling patterns.
Now, a team of researchers led by Michael fox, professor at the Fralin Biomedical Research Institute at VTC and Virginia Tech College of Science, have discovered a key link in how the layers of this processing center develop to decode the eye’s visual cues and regulate key survival instincts in mice. The study was published in the Proceedings of the National Academy of Sciences.
This region of the brain is interesting because it integrates data from multiple sensory inputs, helps form a binocular picture of the world, and then dictates the animal’s innate behaviors – such as fleeing from a predator or hunting for prey – based on this data, “said Fox, who is also director of Virginia Tech College of Science’s School of Neuroscience.
Early in brain development, weeks before a mouse first opens its eyes, neurons extend long axonal processes from the back of the eye, forming the optic nerve. These growing cells eventually branch out to form thousands of complex connections in specific regions of the brain, including the superior colliculus.
How these cells know where to migrate remains largely a mystery, Fox said. But understanding this key phase of development could potentially provide new information that could help researchers in future studies identify ways to regenerate injured optic nerve fibers.
“If our goal is to ever regenerate damaged brain circuitry to restore vision, we first need to know how to get the cell’s axons to develop at a specific destination in the brain,†Fox said.
Fox and his team examined how a specific subtype of optic nerve cells – ipsilateral retinal ganglion cells – reaches the superior colliculus during brain development.
The researchers used a virus to identify the types of neurons with which the retinal ganglion cells made connections once inside the superior colliculus. This led them to identify two proteins that chaperone this circuit formation.
A protein, released by a type of excitatory neuron in the superior colliculus, draws the optic nerve cell closer like a molecular beacon. Once the migrating cell is in the right place, this protein attaches itself to a perfectly matched receptor protein located on the membrane of the nerve cell. This chemical reaction tells the cell that it has reached its destination.
When the flagship molecule – called nephronectin – is absent, a visual layer of the upper colliculus does not form properly and mice find it difficult to hunt their prey.
The superior mouse colliculus has been studied extensively for over 60 years. Although present in all species of mammals, this region of the brain in humans occupies less relative volume and is believed to play a role in stabilizing our image of a moving world by controlling head movements, neck and eyes.
Fox said the study represents a first research collaboration between the National Children’s Hospital and researchers at the Fralin Biomedical Research Institute. He remembers when Virginia Tech’s vice president of health science and technology Michael friedlander Fox connected and Jason triplet, principal investigator at Children’s National Hospital in Washington, DC, seven years ago.
“We talked about studying how these neurons project onto the colliculus in 2013 and have since worked together on many grant-funded projects,†Fox said. “This document was born from these first discussions. “
The co-first authors of the study worked in Fox’s lab at the Fralin Biomedical Research Institute: Jimmy Su, assistant research professor, and Ubadah Sabbagh, former graduate research assistant at the time of the study, who is now a postdoctoral researcher at MIT.
Other research contributors include Yuchin Albert Pan, associate professor at the Fralin Biomedical Research Institute; Yanping Liang, research assistant at the Fralin Biomedical Research Institute; Lucie Olejnikova, former postdoctoral researcher at the Fralin Biomedical Research Institute; Karen Dixon, research technician at the Triplett lab; Ashley Russell, a former postdoctoral researcher at Children’s National Hospital; and Jiang Chen, former postdoctoral researcher at the Fralin Biomedical Research Institute.
This research was funded in part by the National Eye Institute.
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