Is it possible that some people really don't know the meaning of the word fear? A new strain of risk-taking mice is helping scientists study the genetic foundations that underlie the brain's ability to recognize and remember risky or uncomfortable situations.

Researchers have long recognized the amygdala as a vital center for the processing of emotion, including responses such as fear perception, although there is as yet only incomplete understanding of these processes at the molecular level. Previous work from James Olson's lab at the Fred Hutchinson Cancer Research Center (Seattle, WA) has shown that neurogenic differentiation factor 2, an essential transcription factor for neuronal development, seems to have an important function in the amygdala. Mice that entirely lack Neurod2 expression suffer from several neurological problems and die shortly after birth; on the other hand, mice with only one copy of this gene survive to adulthood but, as recently reported by Olson's group, show significant defects in amygdala development—with important behavioral ramifications (Proc. Natl. Acad. Sci. USA, 11 October).

Given the choice between 'protected' and 'unprotected' environments, wild-type mice spent 99% of their time in enclosed areas, whereas the heterozygotes spent almost 90% of their time in the open, suggesting that these mice are far less risk-averse in unconditioned situations. The heterozygotes showed similar reductions in emotional learning in conditioned fear tests, where a negative stimulus (a mild shock) is preceded by an operant signal, suggesting reduced ability to build long-term memory relating to fear-inducing situations. The heterozygous mice showed developmental defects in the basolateral amygdala—a key center for emotional learning related to fear response—and Neurod2 seems to be a key switch for triggering the expression of genes essential to amygdala function. According to Olson, this is clear evidence of the importance of gene dosage for proper brain function. “It's not just whether you have it or not,” he says. “You need the full amount to be a normal mouse.”

Previous research has linked defects of the amygdala with problems in emotional processing, as well as disorders such as schizophrenia. These new findings on Neurod2's vital role in amygdala development and function may provide exciting new opportunities for better understanding the effects of this structure on human behavior, and Olson says that his team is looking forward to extending their research to the analysis of Neurod2 gene variations: “If there are polymorphisms in the gene, then we could do a broader study to see if those polymorphisms match with people who have differences in emotional learning, or fear perception, or schizophrenia, or some of the other diseases that involve the amygdala.”