In previous work, Kandel and his colleagues set out to determine the underlying mechanisms that encode fear in the brain. "We knew from other people's work about the neural pathways involved," Kandel said, "but there was little knowledge of the key genes or the detailed neural circuitry involved. So we thought we would tackle that problem."
The researchers began their studies by searching for genes that were particularly active in the amygdala, a region deep within the brain known to contribute to fear and other emotions. They zeroed in on the lateral nucleus, the portion of the amygdala that receives information from the rest of the body about fearful stimuli. They dissected out individual pyramidal cells, the principal cells in the lateral nucleus, and found two genes, known as gastrin-releasing peptide (GRP) and stathmin, that were much more active in the lateral nucleus than in a part of the brain not thought to be involved in fear, which the researchers analyzed for comparison.
Several years ago, Kandel, Shumyatsky, and their colleagues studied the first of these genes, GRP, in detail and found that it encodes a protein that inhibits the fear-learning circuitry in the brain. GRP does not, however, play a role in innate fear -- demonstrating that the two fear pathways are genetically distinct.
When the scientists moved on to study stathmin, they had few clues as to what role it might play in fear if it was involved at all. "When you go after a gene like this, you have no idea what behavior or biological process it may be involved in," Kandel said. "I think it's the mystery of the thing that creates part of the excitement. Except for thinking that the amygdala was very likely to be involved, we had no way of knowing what the outcome would be."
An indication that stathmin might contribute to fear c
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Contact: Jennifer Michalowski
michalow@hhmi.org
301-215-8576
Howard Hughes Medical Institute
18-Nov-2005