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Male pheromone–stimulated neurogenesis in the adult female brain: possible role in mating behavior.

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Abstract

The regulation of female reproductive behaviors may involve memories of male pheromone signatures, formed in part by neural circuitry involving the olfactory bulb and hippocampus. These neural structures are the principal sites of adult neurogenesis; however, previous studies point to their independent regulation by sensory and physiological stimuli. Here we report that the pheromones of dominant (but not subordinate) males stimulate neuronal production in both the olfactory bulb and hippocampus of female mice, which are independently mediated by prolactin and luteinizing hormone, respectively. Neurogenesis induced by dominant-male pheromones correlates with a female preference for dominant males over subordinate males, whereas blocking neurogenesis with the mitotic inhibitor cytosine arabinoside eliminated this preference. These results suggest that male pheromones are involved in regulating neurogenesis in both the olfactory bulb and hippocampus, which may be important for female reproductive success.

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Figure 1: Male pheromones simultaneously enhance cell proliferation in the SVZ and dentate gyrus.
Figure 2: Male pheromones simultaneously increase neurogenesis in the olfactory bulb and dentate gyrus.
Figure 3: PRLR is expressed in the SVZ and choroid plexus, whereas LHR is expressed in both the SVZ and dentate gyrus of female mice.
Figure 4: LH and PRL independently mediate male pheromone–induced cell proliferation in the DG and SVZ, respectively.
Figure 5: Neurogenesis in the adult female brain is required for female mate preference.

Change history

  • 12 February 2008

    The Supplementary Methods section to this article was not posted at the time the paper was published. The error has been corrected.

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Acknowledgements

We are grateful to K. Markham for providing helpful instruction on the molecular techniques used in this study. We thank A. Chojnacki, B. Kolb, K. Lukowiak, C. Morshead and Q. Pittman for comments on earlier versions of this manuscript. This work was supported by the Canadian Institutes for Health Research and the Academy of Finland. G.K.M. and C.G. were recipients of studentships from the Stem Cell Network of the Canadian Network of Centres of Excellence and the Alberta Heritage Foundation for Medical Research (AHFMR), respectively. S.W. is an AHFMR Scientist.

Author information

Authors and Affiliations

Authors

Contributions

G.K.M. conducted all of the experiments and co-authored the manuscript. E.E.K. and C.G. contributed to the planning and interpretation of the pheromone- and hormone-stimulated neurogenesis studies, T.P, M.P. and I.H. collaborated on studies of LH actions on neurogenesis, LHR immunochemistry and pheromone-stimulated neurogenesis in Lhcgr mice, and S.W. supervised the project and co-authored the manuscript.

Corresponding author

Correspondence to Samuel Weiss.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Paradigm for male pheromone exposure. (PDF 116 kb)

Supplementary Fig. 2

Male pheromones simultaneously increase cell proliferation in the SVZ and DG. (PDF 1984 kb)

Supplementary Fig. 3

Females exposed to novel odors do not have increased proliferation in the SVZ. or DG compared with females exposed to male pheromones. (PDF 267 kb)

Supplementary Fig. 4

Male pheromones simultaneously increase neurogenesis in the dorsolateral corner (DLC) of the SVZ and DG. (PDF 2466 kb)

Supplementary Fig. 5

Short exposure to dominant male pheromones, which result in a lack of increased adult female neurogenesis, also result in a lack of preference for dominant males. (PDF 234 kb)

Supplementary Fig. 6

Plrl?/? females exposed to dominant male pheromones for 7 d do not show a subsequent preference for dominant males. AraC infusions attenuate OB and DG neurogenesis. (PDF 173 kb)

Supplementary Fig. 7

AraC infusions attenuate OB and DG neurogenesis. (PDF 4534 kb)

Supplementary Fig. 8

Females with attenuated dominant male pheromone?induced neurogenesis in the OB and DG do not show a preference for a subordinate or dominant male. (PDF 279 kb)

Supplementary Fig. 9

Assay to determine novel odor detection and habituation. (PDF 314 kb)

Supplementary Methods (PDF 177 kb)

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Mak, G., Enwere, E., Gregg, C. et al. Male pheromone–stimulated neurogenesis in the adult female brain: possible role in mating behavior.. Nat Neurosci 10, 1003–1011 (2007). https://doi.org/10.1038/nn1928

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