Female odors lead to rapid activation of mitogen-activated protein kinase (MAPK) in neurons of the vomeronasal system

Pheromonal mediation of reproductive function proceeds along a neuroanatomical pathway that connects the vomeronasal organ (VNO) at the periphery with downstream target-sites in the amygdala and hypothalamus. The MAPK pathway is a prominent cascade linking receptor activation to induction of effectors such as c-Fos. We addressed the question: Does a specific pheromone stimulus lead to activation (phosphorylation, P) of MAPK in the VN system of the male mouse? Phosphorylation of MAPK in the VN system was evaluated 15-30 min and 1.5-2 h after exposure to female odors, using immunocytochemical techniques. A rapid and transient cytoplasmic expression of PMAPK was noted in the VNO with a unique distribution of the expressing neurons in columns extending over the entire basal to apical axis. A rapid and sustained expression was noted in most amygdaloid and hypothalamic VN target-sites and also in a few amygdaloid and hypothalamic sites outside the traditional VN system. The extent of expression and the subcellular compartmentalization (nucleus, cytoplasm, processes) of PMAPK were region-dependent. Of the VN target-sites, the accessory olfactory bulb (AOB) stood out in the lack of expression of PMAPK, in the high expression of the MAPK enzyme itself and in the massive of expression of c-Fos. This expression profile implicates another pathway(s) in mediating VNO signaling to the AOB. Our results are the first to demonstrate the use of PMAPK to trace functional pathways. Based on the wide cellular and intracellular expression of phosphorylated MAPK in the VN system, we propose that the MAPK pathway plays an important role in mediating female pheromone signaling in the male mouse.