December 19, 2002
Howard Hughes Medical Institute researchers have developed sophisticated microscopy techniques that permit them to watch how the brains of live mice are rewired as the mice learn to adapt to new experiences.
“This finding was quite unexpected, because the traditional view of neural development has been that when animals mature, the formation of synapses ceases.”
Their studies show that rewiring of the brain involves the formation and elimination of synapses, the connections between neurons. The technique offers a new way to examine how learning can spur changes in the organization of neuronal connections in the brain.
The researchers, postdoctoral fellow Josh Trachtenberg, graduate student Brian Chen and
Karel Svoboda, a Howard Hughes Medical Institute investigator at Cold Spring Harbor Laboratory, published their findings in the December 19/26, 2002, issue of the journal Nature.
According to Svoboda, researchers had previously shown that the adult brain has a capacity to reorganize in response to new experience. However, it is not clear how this reorganization might occur. Svoboda and his colleagues wanted to see whether learning could induce restructuring of the neural circuitry in the brain that could not be picked up with conventional techniques.
"Since we had this great tool to look at the brain at unprecedented resolution we did not know what to expect and we began with no preconceived notions of what we might see in these animals," said Svoboda. "Our first observations of the large-scale structure of neurons, their axons and dendrites, revealed that they were remarkably stable over a month." Dendrites and axons are highly branched structures, where dendrites are the input side of neurons and axons the output side.
"However, when we zoomed in closer, we found that some spines on dendrites appeared and disappeared from day to day," said Svoboda. These spines stipple the surface of dendrites, like twigs from a branch, and form the receiving ends of synapses, which are the junctions between neurons where neurotransmitters are released.
This finding was quite unexpected, because the traditional view of neural development has been that when animals mature, the formation of synapses ceases, which is indicated by stable synaptic densities, said Svoboda. However, the flaw in this view has been that a stable density only indicates a balanced rate of birth and death of synapses. It doesn't imply the absence of the formation of new synapses, but it was often interpreted that way.
To study those kinds of changes in a living animal, Svoboda and his colleagues started with transgenic mice that were engineered to produce green fluorescent protein within neurons in a portion of the brain that processes tactile sensory inputs from the whiskers. To observe changes in these neurons at high resolution, the scientists constructed a 2-photon laser scanning microscope. This microscope uses an infrared laser to excite green fluorescent protein in neurons, deep in the brain, through a tiny glass window installed in a portion of the mouse's skull.
In further studies, Svoboda and his colleagues plan to explore how brain circuitry changes on a larger-scale, by observing mice engineered to express different fluorescent proteins in different populations of neurons.
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