Exposure to gonadal steroids early in life has lasting (in many cases, permanent) effects on the brain. The nature of this “cellular memory” for hormone exposure has been mysterious but recent work demonstrates that epigenetics (literally, “above” or “on top of” genetics) are involved. We hypothesized that epigenetic modifications are required for the development of neural sex differences. Currently, we are exploring the effects of blocking DNA methylation on the development of sex differences in cell phenotype in the brain.
The mammalian fetus develops in the relatively sterile environment of the womb, and suddenly encounters a complex world of microbes at birth. We found that exposure to microbes at birth is important to brain development, because neuronal cell death and microglial colonization of the brain are altered in mice born into a germ-free environment. Because the gut harbors by far the largest population of microbes, we are currently investigating the mechanisms whereby information about the gut microbiome reaches the neonatal brain.
Cell-Death Marker in the Preoptic Area
Role of Parturition
Cell death peaks around the time of birth in several brain regions of the mouse. In this project, we are studying how birth influences cell death in the brain by manipulating the mode or timing of birth. We find that Cesarean born mice have increased cell death in several brain regions compared to vaginally born mice. By studying mice born one day early or one day late, we are also determining whether the timing of birth drives the timing of neuronal cell death.
Neural Basis of Social Behavior
Many behavioral disorders related to social behavior show striking sex differences in incidence. Sexual differentiation of the brain likely contributes to these differences. We are studying the sexually dimorphic vasopressin innervation, a system that has been implicated in social behavior in adult animals. We use a combination of psychopharmacological and genetic approaches to test how vasopressin controls social behavior in juvenile rodents and focus on sex differences in this process.