Current Research Interests
Social defeat stress has emerged as an important model of stress-induced psychiatric disease. Although depression is more common in women, most studies of social defeat are conducted on male mice or rats. We study a monogamous species (the California mouse) to investigate how social stress impacts brain and behavior in both males and females. Unlike domestic rats and mice, female California mice aggressively defend territories. Our work has discovered sex-specific behavioral and neurobiological changes induced by social stress. Further understanding of how stress impacts the brain in males and females could lead to more optimized treatment for depression and anxiety.
New NIH policies encourage basic research programs to consider sex as a biological variable (SABV) and include both males and females in experiments. Our research with California mice provides an outlet for testing hypotheses in females that are developed with transgenic mice. We are very interested in collaborating with labs seeking to test hypotheses in females. A sequenced brain transcriptome and online brain atlas (brainmaps.org) are available for California mice. See the main page or contact Brian Trainor for more information.
New NIH policies encourage basic research programs to consider sex as a biological variable (SABV) and include both males and females in experiments. Our research with California mice provides an outlet for testing hypotheses in females that are developed with transgenic mice. We are very interested in collaborating with labs seeking to test hypotheses in females. A sequenced brain transcriptome and online brain atlas (brainmaps.org) are available for California mice. See the main page or contact Brian Trainor for more information.
Complementary neural circuits affecting social approach and social vigilance
Steinman et al. 2016 and Duque-Wilckens et al. 2016
Oxytocin (blue) and vasopressin (green) neurons in the paraventricular nucleus co-stained with c-fos (red).
Oxytocin is a well-known modulator of social behaviors and has been put forth as a possible therapeutic for anxiety and depression. In some studies using human participants, intranasal oxytocin enhances social approach related behaviors. However, other studies (especially in women) report that intranasal oxytocin increases social anxiety. How can the same neuropeptide exert such different effects on behavior? Our central hypothesis is that oxytocin acts in the mesolimbic dopamine system to promote social approach, whereas oxytocin acts in the bed nucleus of the stria terminalis (BNST) to enhance social anxiety. If supported, this hypothesis could help reconcile apparently contradictory findings in both human and animal studies of oxytocin function. We are testing hypothesis in both males and females, because social anxiety is almost twice as prevalent in women as it is in men. A key finding by Duque-Wilckens et al. 2018 is that oxytocin receptors in the BNST are necessary for the expression of stress-induced social vigilance in females (see video below).
Bed nucleus of the stria terminalis: Brain derived neurotrophic factor
Greenberg et al. 2014
Social stress increases BDNF protein in the BNST of females but not males. ** p < 0.01 vs control female.
The bed nucleus of the stria terminalis (BNST) sits just anterior to the nucleus accumbens and is an important node connecting the mesolimbic system with hypothalamic and limbic nuclei that regulate social behavior. Social defeat stress increases brain derived neurotrophic factor (BDNF) protein in the BNST of female but not male California mice. Infusion of an antagonist to TrkB, an important receptor activated by BDNF, blocks stress induced social withdrawal in females but not males. These data show that functional sex differences in the BNST contributes to sex differences in behavioral responses to stress.