Conditional Deletion of ERK5 MAP Kinase in the Nervous System Impairs Pheromone Information Processing and Pheromone-Evoked Behaviors

Junhui Zou,Daniel R Storm,Zhengui Xia,Allan Siegel

doi:10.1371/journal.pone.0076901

Abstract

ERK5 MAP kinase is highly expressed in the developing nervous system but absent in most regions of the adult brain. It has been implicated in regulating the development of the main olfactory bulb and in odor discrimination. However, whether it plays an essential role in pheromone-based behavior has not been established. Here we report that conditional deletion of the Mapk7 gene which encodes ERK5 in mice in neural stem cells impairs several pheromone-mediated behaviors including aggression and mating in male mice. These deficits were not caused by a reduction in the level of testosterone, by physical immobility, by heightened fear or anxiety, or by depression. Using mouse urine as a natural pheromone-containing solution, we provide evidence that the behavior impairment was associated with defects in the detection of closely related pheromones as well as with changes in their innate preference for pheromones related to sexual and reproductive activities. We conclude that expression of ERK5 during development is critical for pheromone response and associated animal behavior in adult mice.

Highlights

Vertebrates rely on chemosensory mechanisms to detect food sources, recognize social and mating partners, and avoid predators
We previously reported that conditional deletion of ERK5 in neural stem cells (ERK5 cKO) abolishes main olfactory bulb (MOB) neurogenesis [19]
Since pheromone can be detected by both MOB and accessory olfactory bulb (AOB), we examined if ERK5 deletion affects the development of AOB

Summary

Introduction

Vertebrates rely on chemosensory mechanisms to detect food sources, recognize social and mating partners, and avoid predators. Male mice lacking functional CNGA2 (cyclic nucleotide-gated channel alpha 2) or AC3 (type-3 adenylyl cyclase), proteins that are required for the signal transduction through the MOE but are not expressed in the VNO, do not exhibit male dominance and male sexual activity [10,11]. Both the MOE/MOB and VNO/AOB systems participate in pheromone detection and associated behaviors

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