Genomic imprinting mediates sexual experience-dependent olfactory learning in male mice

doi:10.1073/pnas.0609471104

Genomic imprinting mediates sexual experience-dependent olfactory learning in male mice

*Sub-Department of Animal Behaviour, University of Cambridge, High Street, Madingley, Cambridge CB3 8AA, United Kingdom; and
^†Department of Psychology, Columbia University, New York, NY 10027

Edited by Donald W. Pfaff, The Rockefeller University, New York, NY, and approved February 21, 2007 (received for review October 25, 2006)

Abstract

Mammalian imprinted genes are generally thought to have evolved as a result of conflict between parents; however, recent knockout studies suggest that coadaptation between mother and offspring may have been a significant factor. We present evidence that the same imprinted gene that regulates mammalian maternal care and offspring development also regulates male sexual behavior and olfaction. We have shown that the behavior of male mice carrying a knockout of the imprinted gene Peg3 does not change with sexual experience and that the mice are consequently unable to improve their copulatory abilities or olfactory interest in female odor cues after mating experience. Forebrain activation, as indexed by female odor-induced c-Fos protein induction, fails to increase with sexual experience, providing a neural basis for the behavioral deficits that the male mice display. The behavioral and neural effects of the Peg3 knockout show that this imprinted gene has evolved to regulate multiple and varied aspects of reproduction, from male sexual behavior to female maternal care, and the development of offspring. Moreover, sexual experience-driven behavioral changes may represent an adaptive response that enables males to increase their reproductive potential over their lifespan, and the effects we have found suggest that the evolution of genomic imprinting has been influenced by coadaptation between males and females as well as between females and offspring.

Footnotes

^‡To whom correspondence should be addressed. E-mail: wts2102{at}columbia.edu
Author contributions: W.T.S., J.P.C., and E.B.K. designed research; W.T.S. performed research; W.T.S. analyzed data; and W.T.S., J.P.C., F.A.C., and E.B.K. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
Abbreviations:

AOB,

accessory olfactory bulb;

B6,

C57BL/6J;

BNSTp,

posterior part of the bed nucleus of the stria terminalis;

KO,

knockout;

MeAmgA,

anterior medial amygdala;

MeAmgPD,

posterior–dorsal medial amygdala;

MPOA,

medial preoptic area;

NAc,

nucleus accumbens;

p3-SE,

sexually experienced Peg3-KO;

p3-V,

virgin Peg3-KO;

VMH,

ventromedial hypothalamus;

wt,

wild type;

wt-SE,

sexually experienced wt;

wt-V,

virgin wt.