A sex comparison of the anatomy and function of the main olfactory bulb–medial amygdala projection in mice

We previously reported that some main olfactory bulb (MOB) mitral/tufted (M/T) cells send a direct projection to the “vomeronasal” amygdala in female mice and selectively respond to volatile male mouse urinary odors. We asked whether MOB M/T cells that project to the vomeronasal amygdala exist in male mice and whether there is a sexually dimorphic response of these neurons to volatile male urinary pheromones. Gonadectomized male and female mice received bilateral injections of the retrograde tracer, Cholera toxin-B (CTb) into the medial amygdala (Me), which is part of the vomeronasal amygdala. All subjects were then treated with estradiol benzoate and progesterone before being exposed to volatile male urinary odors whereupon they were sacrificed 90 min later. Sections of the MOB were immunostained for Fos protein and/or CTb. Male mice, like females, displayed a small population of MOB M/T cells that project to the Me. While the general localization of these cells was similar in the two sexes, there were statistically significant sex differences in the percentage of MOB M/T cells in the anterior and posterior medial segments of the MOB that were retrogradely labeled by CTb. Male urinary volatiles stimulated equivalent, significant increases in Fos expression by MOB M/T neurons projecting to the Me in the two sexes. By contrast, in the same mice exposure to male urinary volatiles stimulated a significant increase in Fos expression by mitral cells in the accessory olfactory bulb (AOB) only in female subjects. Thus any sexually dimorphic behavioral or neuroendocrine responses to male urinary volatiles likely depend on the differential processing of these odor inputs in the AOB and/or other downstream forebrain structures after their detection by the main olfactory system.

Research Highlights▶A direct projection from the main olfactory bulb (MOB) to the medial amygdala exists. ▶This MOB projection is sexually dimorphic in mice. ▶Male urinary odors activate this MOB projection equally in males and females.