9 December 2005, EMBL Monterotondo (Rome)
Nature via nurture in the mouse
Cornelius Gross, EMBL Monterotondo
Mutations in genes controlling serotonergic neurotransmission have been shown to alter anxiety-related behaviors in mice, monkeys and man. Recent human data have shown that adverse life experiences can moderate the effect of these mutations suggesting that genes and environment can interact to determine personality traits. We have used the mouse as a model to understand the molecular mechanisms by which mutations in the serotonergic system moderate anxiety-related behavior. We discovered that loss-of-function mutations in the serotonin 1A receptor are associated with increased anxiety-related behavior and that this defect stems from a critical role of this receptor in the development of brain circuits controlling the evaluation of emotional stimuli. We have also shown that loss-of-function mutations in the serotonin transporter gene are associated with increased anxiety-related behavior but that, like in humans, this effect depends on the presence of adverse environmental factors. Our results demonstrate that changes in the wiring of the brain during development that can lead to life-long alterations in anxiety behavior and show that this phenomenon is controlled by complex interactions between genes and environment.