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 (in which social defeat protocols in females are currently unvailable). We are very interested in collaborating with labs seeking to test hypotheses in females. A sequenced brain transcriptome and additional neuroanatomical resources should be available by the end of 2016. 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 (in which social defeat protocols in females are currently unvailable). We are very interested in collaborating with labs seeking to test hypotheses in females. A sequenced brain transcriptome and additional neuroanatomical resources should be available by the end of 2016. Contact Brian Trainor for more information.
Nucleus accumbens: Dopamine receptors
Campi et al. 2014
Injection sites in the nucleus acumbens of California mice.
This paper shows that social defeat stress increases total dopamine and dopamine metabolite content within the nucleus accumbens of both males and females. Blocking increased dopamine activity with an infusion of D1 dopamine receptor antagonist increased social interaction in females exposed to social stress. Intriguingly, a D1 agonist infusion in to the nucleus accumbens is sufficient to induce social withdrawal in females but not males with no prior exposure to social stress. These data show that suggest that a mechanism downstream from dopamine receptors blocks social withdrawal in male California mice exposed to social stress. We are currently exploring kappa opioid receptor signaling as a possible mechanism
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.
Neuropeptides: Oxytocin and vasopressin
Steinman et al. 2015, Steinman et al. 2016
Oxytocin (blue) and vasopressin (green) neurons in the paraventricular nucleus co-stained with c-fos (red).
Oxytocin and vasopressin are important neuropeptides that modulate social behaviors. In females social defeat increases the activity of oxytocin neurons in the bed nucleus of the stria terminalis and paraventricular nucleus. Interestingly, intranasal oxytocin has no effect on social interaction behavior in stressed females, but reduces social interaction in females that have not experienced stress. Together, these data suggest that stress increases the activity of oxytocin neurons in the brain, which in turn reduce social interaction behavior. Ongoing research is investigating the specific neural pathways that mediate the effect of oxytocin in stressed and unstressed mice. In males, although social defeat has no effect on oxytocin, stres reduces the expression of vasopressin in the hypothalamus.
