Brain aromatase and its relationship with parental experience and behavior in male mice

Paula Duarte Guterman ^1* Dimitri A Skandalis ² Ariane Merkl ³ Diana B Geissler ³ Günter Ehret ^3*

• ¹ Departmenof Psychology and Centre for Neuroscience, Brock University, St. Catharines, Canada
• ² Psychological & Brain Sciences and Johns Hopkins Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, United States
• ³ Institute of Neurobiology, University of Ulm, Ulm, Germany

In most mammals, paternal care is not mandatory for raising offspring. In house mice, experience with pups governs the extent and quality of paternal care. First-time fathers undergo a dramatic transition from ignoring or killing pups to caring for pups. The behavioral shift occurs together with changes in brain estrogen signaling as indicated by changes in estrogen receptor presence and distribution in multiple areas regulating olfaction, emotion, and motivation. Here, we report changes in the expression of aromatase, the enzyme converting testosterone into estrogen, as an indirect measure of estrogen synthesis. The amount of paternal experience (5 or 27 days) was associated with increased numbers of immunocytochemically-identified aromatase expressing cells in the medial and cortical amygdala, posterior piriform cortex, and ventromedial hypothalamus. Functionally, these changes can be related to the disappearance of aggression or neglect towards pups when firsttime fathers or, even more, well-experienced fathers are handling their own pups. In the lateral septum, the anterior piriform cortex and to some extent in the medial preoptic area, parental experience increased the number of aromatase-positive cells only in fathers with 27 days of experience, and only in the right hemisphere. This is a new case of brain-functional lateralization due to experience that has activated certain instinctive behavior. Nuclei/areas associated with maternal care (medial preoptic area, bed nucleus of stria terminalis, nucleus accumbens) exhibited a left-hemisphere advantage in aromatase expressing cells, both in pupnaïve and pup-experienced males. This newly found lateralization may contribute to the lefthemisphere dominant processing and perception of pup calls to release parental behavior. In general, the experience-dependent changes in aromatase expression we observed in most brain areas did not mirror the previously reported changes in estrogen receptors (ERα) when pup-naïve males became pup-caring fathers. Hence, paternal behavior may depend in a brain area-specific way on the differential action of estrogen through its receptors and/or direct local modulation of neural processing.