Embryonic transcription factor expression in mice predicts medial amygdala neuronal identity and sex-specific responses to innate behavioral cues

Within the brain, a set of interconnected structures called the limbic system is involved in emotion, motivation and memory. This system – and in particular a structure called the medial amygdala – also contributes to behavioral drives that help an animal to survive and reproduce. These include the drive to avoid predators, to defend territory, and to find a mate. Such behaviors are thought to be inborn or innate. This means that animals display them instinctively whenever specific triggers are present, without the need to learn them beforehand. However, just as a computer must be programmed to perform specific tasks, these innate behavioral responses must also be programmed into the brain. Given that animals do not learn these behaviors, Lischinsky et al. reasoned that specific events during the development of the brain must provide the animal’s brain with the necessary instructions. To test this idea, they studied how the development of the medial amygdala in mouse embryos may give rise to differences in innate mating behavior seen between male and female mice. The medial amygdala contains many subtypes of neurons, which show different responses to sex hormones such as estrogen and androgen. Lischinsky et al. show that two sets of cells give rise to some of the different neurons of the adult medial amygdala. One set of these precursor cells makes a protein called Dbx1 and the other makes a protein called Foxp2. These two sets of precursors generate medial amygdala neurons with different arrays of sex hormone receptors in male and female mice. Moreover, while the two sets of medial amygdala neurons are activated during aggressive encounters, they show different patterns of activation in male and female animals during mating. These findings suggest that the development of Dbx1-derived and Foxp2+ neurons in the medial amygdala helps program innate reproductive and aggressive behaviors into the brain. The new findings also provide insights into why these behaviors differ in male and female mice. The next challenge is to identify the inputs and outputs of these two distinct subpopulations of medial amygdala neurons. This should make it possible to work out exactly how these populations of cells control innate behaviors in male and female animals.