Ready, Set, Switch: Young neurons stop building transmitters, start building receivers (Neuroregeneration)
Authors: Beckman Mary 
Published: August 2003

Developing neurons in the eye suddenly drop construction on broadcast equipment and gear up for listening, researchers have found. This switch permanently alters a neuron's capacities. The work suggests the existence of a previously unknown step in nerve cell development that is crucial for nervous system repair.
Many neurons are like one-way streets: Impulses travel in a single direction. Splayed bristles of the cell membrane called dendrites capture messages from outside the cell and send them down a sinewy filament called an axon that relays the message to other cells. Broken axons underlie most neuron injuries, and researchers have been struggling for decades to repair and regenerate these transmission lines. Previous work suggested that cells in the central nervous system called glia exude compounds that prevent axons from growing back, but Goldberg and colleagues questioned whether these nonneuronal cells are solely to blame. Perhaps the neurons refuse to grow axons, they proposed.
To determine whether neurons could extend axons if glia are absent, the team purified neurons called retinal ganglion cells (RGCs) from rats at different times during development and after birth. They compared the rates of axon growth in culture and found that RGCs from 20-day-old embryos--2 days before birth--lengthened the fastest. By 2 days after birth, the rate of extension dropped 10-fold. To distinguish whether older RGCs needed a prod or had changed gears permanently, the team took embryonic and 8-day-postnatal RGCs and either cultured them with cells that normally stimulate axon growth in the central nervous system or transplanted them into an embryo's brain that was busily growing axons. Under both conditions, young and old cells produced axons that grew at the rates previously observed. This result suggests that older RGCs lose the capacity to extend quickly. The team then let embryonic RGCs sit in culture past the age at which they should have started to drag. The neurons retained their talent for rapid axon elongation, suggesting that they take their cue on when to slow down from a signal in the retina.
The researchers subsequently found that amacrine cells--neurons that normally pass messages to RGCs--stopped axonal growth. Additional experiments suggested that the conclusion of axon construction coincides with an explosion of new dendrite production, suggesting that a single switch squelches axon expansion and spurs dendrite growth. Lead researcher Ben Barres, a Stanford University neuroscientist, says that before we can use this discovery to regenerate injured neurons, we need to know whether brain neurons behave like retinal neurons.
The work shows that inhibitory signals from the environment are not the only forces that put the kibosh on axon growth, says neuroscientist Jeffrey Macklis of Harvard Medical School in Boston; the cell itself also forgets how to grow them. The results "provide a better road map for what needs to be controlled to get axon regeneration," he says. Perhaps in the future, the neurons will hear--and heed--neuroscientists.
--Mary Beckman

J. L. Goldberg, M. P. Klassen, Y. Hua, B. A. Barres, Amacrine-signaled loss of intrinsic axon growth ability by retinal ganglion cells.
Science
296
, 1860-1864 (2002).
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