December 18, 2003
La Jolla, CA – Nerve cells firing in spontaneous waves create the brain’s first sharp visual images during a short but critical phase of development, Salk Institute researchers have found. The study may lead to ways to better treat nerve cell injury and even treatments of diseases that occur in later life, like Parkinson’s.
Previous work by Harvard Professor Carla Shatz and others has shown that before vision develops, the immature retina spontaneously generates a coordinated cascade of nerve cell activity. This spontaneous activity has been implicated in developing patterns of connections from the two eyes within the brain that are responsible for binocular vision. In the most recent study, Salk and UCSD researchers show for the first time that this early spontaneous activity is also critical for creating the precise connections in the brain to ensure sharp visual acuity later in life. Without these precise connections, the brain cannot process a sharp vision of the world. The study appears in the December 18 issue of Neuron.
Knowing how the brain wires itself precisely during development could yield clues for treating diseases where this precise circuitry has unraveled. Nerve trauma and diseases where nerve cells are degenerated, like Parkinson’s, could be targets of new drugs arising from this research.
Dennis O’Leary, professor of molecular neurobiology, Todd McLaughlin, a postdoctoral fellow at the Salk, Marla Feller, an assistant professor at the University of California, San Diego and UCSD doctoral student, Christine Torborg discovered that during one critical week after birth, before baby mice can see, they need to precisely coordinate retinal nerve cell activity to create what’s called a retinotopic map, the brain’s detailed blueprint of the outside world relayed to it from the retina. Without these waves of nerve cell input, nerve cells “have very diffuse connections to visual centers in the brain, and lack the precise arrangement needed to produce an accurate map and proper vision,” said O’Leary.
“This study answered the question of how natural coordinated activity in nerve cells produce detailed maps in the visual processing centers of the brain,” he said. “We found how the brain works to remodel a coarse set of connections into a detailed map. This work also may tell us how other, non-visual nerve cell connections are made in the brain, and may help design better ways to restore effective nerve cell connections in cases of trauma or degenerative disorders like Parkinson’s disease.”
Nerve cell activity in the eye and visual areas of the brain is random and rapid before the young brain is exposed to light. Nerve cells have a tendency to “overshoot” their targets in the brain at this stage, creating a disorganized jungle of nerve connections; as the brain develops it organizes these nerve connections into an efficient processor of visual information.
By using mice genetically-engineered to lack the key neurotransmitter receptor that coordinates this wave-like activity in the eye, O’Leary and his colleagues were able to identify the nerve cells that coordinated their firing activities to eliminate unnecessary nerve cell connections. Once these coordinated activities were completed in normal mice, the brain and eye were left with precise connections and later, when real vision begins, a detailed image of the environment.
“The study helped us evaluate how these precise maps form,” said O’Leary. “These findings have many implications, but most importantly, we can see if disruptions in this process possibly lead to vision disorders in humans.”
The research was supported by grants from the National Eye Institute, the Klingenstein, McKnight and Whitehall foundations, the March of Dimes, and the National Science Foundation.
The Salk Institute for Biological Studies, located in La Jolla, Calif., is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and conditions, and the training of future generations of researchers. Jonas Salk, M.D., founded the institute in 1960 with a gift of land from the City of San Diego and the financial support of the March of Dimes Birth Defects Foundation.