Our experiences
in the world leave their mark on the architecture of our brain
when they cause neurons or nerve cells to forge new
connections with each other. Neuroscientists believe that when neurons
are stimulated, calcium ions flow into cells and alter the activity
of genes. But how does the calcium stimulate structural changes in
the neurons? UCSD biology professor Anirvan Ghosh and colleagues
from his former lab at Johns Hopkins University believe they may
have found the answer with the discovery and study of the CREST (calcium
responsive transactivator) gene in mice.
CREST, a gene that is also
found in
humans, is switched on when calcium flows into neurons. It is the
first example of a transcription factor—a protein that turns
genes on and off—that appears to be specifically required for
the development of neurons after birth. Neurons from normal mice
develop a highly branched tree-like structure, but neurons from mice
without the CREST gene grow few branches, remaining linear like a
plant shoot.
“The brains of mice lacking
CREST appear normal at birth, but do not develop normally in response
to sensory experience after birth,” say Ghosh. “This
parallels some learning disorders in humans where the child appears
normal initially, but by the age of two or three years it becomes
clear that there are failures in the acquisition of new knowledge.”
Immediately after birth, CREST protein is made in several regions
of the brain. However, in adults, CREST protein production is limited
to a region of the brain known as the hippocampus, which plays
an important role in learning and memory.
Because of this, Ghosh
suspects
that CREST may be necessary in adults for the storage of new
memories and the ability to learn. His laboratory is currently
developing
mice in which CREST protein production is normal throughout most
of development, but then shuts off in the hippocampus when the
mice reach adulthood. In this way, the researchers will be able
to test
the specific role of CREST in learning and memory in adults.
And if scientists can identify learning disorders associated with
the
absence of the CREST gene, Ghosh believes it might one day be
possible to treat them through gene therapy. 
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