How does the cortex, the brain's executive in charge of high-level thinking and planning, go from a uniform blob of brain matter to well-defined areas with specific sensing, cognition and movement tasks?
A leading neuroscientist at MIT and one from the University of California at San Francisco (UCSF) report in the Nov. 4 special issue of Science dedicated to the brain that the controversy is over: The "protomap" and "protocortex" theories of brain development are dead.
The cerebral cortex is a sheet of around 10 billion neurons divided into distinctly separate areas that process particular aspects of sensation, movement and cognition. To what extent are these areas predetermined by genes or shaped by the environment? The protomap and protocortex theories developed before 1990 claimed, respectively, that the task-specific regions of the cortex are spawned by a zone of "originator" cells; or that long nerve fibers from the thalamus, a large ovoid mass that relays information to the cortex from other brain regions, are activated by external stimuli to impose identity on the homogeneous blob.
New evidence indicates that the development of cortical areas involves "a rich array of signals," an interwoven cascade of developmental events, some internal and some external, according to co-authors Mriganka Sur, Sherman Fairchild Professor of Neuroscience at the Picower Institute for Learning and Memory and the MIT Department of Brain and Cognitive Sciences, and John L. R. Rubenstein of UCSF.
"Recent evidence has altered researchers' understanding of how cortical areas form, connect with other brain regions, develop unique processing networks and adapt to changes in inputs," Sur said. "Understanding basic mechanisms of cortical development is central to understanding disorders of development."
Sur, chair of the Department of Brain and Cognitive Sciences at MIT, is leading an ambitious, multifaceted approach to understanding the genetic, molecular and behavioral aspects of autism.
In the Science review article, "Patterning and Plasticity of the Cerebral Cortex," Sur and Rubenstein point out that transcription factors are key. A transcription factor is a protein that binds DNA at a specific site where it regulates transcription, or the process of copying genetic material.
In the brain's early prenatal development, transcription factors control the birth and growth of new neurons, neurons' movement and connectivity within the brain, and which ones live and which are killed off.
Later, at a critical point in development, activity in the form of outside stimulation refines the brain's topography and networks to create the specific functions and areas of the postnatal mammalian brain.
This work is supported by the National Institutes of Health, the Marcus Fund and the Simons Foundation.