Under Construction

Temporary scaffolding guides nerves in the developing brain

r· e most ambitious architectural projects, the developing brain seems to need scaffolding during

construction. And, like the angular, skeletal framework that encases build­ings, this scaffolding appears to be dis­mantled when construction is com­plete. At least that is the substance of a growing body of evidence, some of which was presented at the November 1991 Society for Neuroscience meeting.

"A theme in development is 'Here to­day, gone tomorrow,' '' says Carla ]. Shatz, professor of neurobiology at Stanford University, whose work first elucidated the function of one type of transient scaffolding in the developing brain. In the future, Shatz says, some birth defects such as cerebral palsy may be associated with these early struc­tures. "You can't base your thinking just on what's in the adult brain," she adds. ''The early brain is very different."

The existence of scaffolding could help explain how the connections from certain neurons reach their final desti­nation-before it exists. For example, during development, the long nerve fibers that carry messages from the retina must reach into an area of the brain called the visual thalamus. From there, axons from the visual thalamus grow on to make connections with oth­er neurons in layer four of the visual cortex, the outer, convoluted part of the brain. But, like overeager homebuy­ers, these axons arrive just below the cortical layer before the house-or even the street-is built.

Several years ago Shatz and her col­leagues found that a group of short­lived cells serve as intermediate targets and tour guides to the incoming axons. These subplate neurons, as they are called, appear just below the visual cor­tex and seem to direct the thalamic ax­ons to their final destination. "These neurons act as a temporary linkage," she says. (No one seems to know how subplate neurons get their directions.)

Although the existence of subplate neurons has long been recognized, some researchers assumed they were an evolutionary vestige-rather like the tailbones at the end of the human spinal column-or a waiting station. In a series of experiments in cats, howev­er, Shatz and her colleagues demon­strated the pivotal role of these neu­rons. When Shatz removed the subplate neurons early in development, thalamic axons roamed around below the corti-

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cal plate, the home of the forthcoming layer-four neurons. They never. made it to the cortex.

In a recent experiment, Shatz re­moved the subplate neurons later in de­velopment. She found the cats did not develop what are called ocular-domi­nance columns, the fine-tuned structure of the visual cortex organized accord­ing to whether cells respond to stimuli from the left or right eye. Whereas some ocular dominance depends on incom­ing visual stimuli, the brain apparently had no means by which to develop the organization without the subplate neu­rons. In other words, "if we get rid of the subplate neurons early, the axons don't find the right city," Shatz ob­serves. "If we get rid of them later, the axons don't find the right address."

Although Shatz, like many scientists studying development in the brain, fo­cuses on the visual system, she says her laboratory has evidence that sub­plate neurons play the same organi­zational role in other areas of the cor­tex. Subplate neurons seem to forge the first connections between the cortex and subcortical areas early in develop­ment, when the distances to travel are small.

In normal development, the subplate neurons disappear once the subcortical axons reach the right address. The re­gion in which they reside becomes white matter, which functions as a pathway for incoming and outgoing axons in lat­er development. Shortly before they die, the subplate neurons lose their re­ceptors for nerve growth factor.

The idea of transient structures in the developing brain is an old one, but "it is currently going through a useful renais­sance," comments Dale Purves, profes­sor of neurobiology at Duke University. In 1972 Pasko Rakic, professor of neu­roanatomy at Yale University, reported that radial glial cells-nerve cells that surround neurons and that, until recent­ly, were considered the wallflowers of the nervous system-support neurons as they migrate to their place of resi­dence in the developing brain. Just like sub plate neurons, radial glial cells are not present in the adult brain. Simpler nervous systems in fish and insects also have early-forming neurons that establish pathways and then die, just like subplate neurons.

But although "there are some other examples of vertebrate neurons that may appear transiently, none of those are implicated so profoundly in devel­opment as the subplate neurons," com­ments Corey S. Goodman, professor of neurobiology at the University of Cali­fornia at Berkeley. "This is a very novel discovery." -Marguerite Holloway

© 1991 SCIENTIFIC AMERICAN, INC