Bilateral damage to the sexually dimorphic medial preoptic area/anterior hypothalamus of male ferrets causes a female-typical preference for and a hypothalamic Fos response to male body odors

Abstract

Previous studies showed that bilateral lesions of the male ferret's preoptic area/anterior hypothalamus (POA/AH), centered in the sexually dimorphic nuclei present in this region, caused subjects to seek out a same-sex male, as opposed to a female conspecific. Male subjects with POA/AH lesions (which were also castrated and given estradiol) displayed female-typical receptive behavior in response to neck gripping by a stimulus male, implying that subjects' approaches to a same-sex conspecific were sexually motivated. We asked whether the effect of POA/AH lesions on males' partner preference reflects a shift in the central processing of body odorant cues so that males come to display a female-typical preference to approach male body odorants. Sexually experienced male ferrets in which electrolytic lesions of the POA/AH caused bilateral damage to the sexually dimorphic male nucleus (MN) resembled sham-operated females by preferring to approach body odors emitted from anesthetized male as opposed to female stimulus ferrets confined in the goal boxes of a Y-maze. This lesion-induced shift in odor preference was correlated with a significant increase in the ability of soiled male bedding to induce a Fos response in the medial POA of males with bilateral damage to the MN-POA/AH. No such partner preference or neural Fos responses were seen in sham-operated males or in other groups of males with POA/AH lesions that either caused unilateral damage or no damage to the MN-POA/AH. Male-typical hypothalamic processing of conspecifics' body odorants may determine males' normal preference to seek out odors emitted by female conspecifics, leading to mating and successful reproduction.

Fig. 1

Schematic representation (240 μm intervals between coronal sections) of the extent of the damage caused by electrolytic lesions of the medial preoptic area/anterior hypothalamus (mPOA/AH) of male ferrets. Light-gray areas show the maximal extent of lesion damage for any of the individual subjects included in a particular group. Dark-gray areas show the overlapping lesion damage that was present in all members of a particular group. Left panel: subjects with extensive lesions of the mPOA/AH but no damage to the sexually dimorphic male nucleus of the POA/AH (MN-POA/AH) (n=16). Middle panel: subjects with unilateral damage to the MN-POA/AH (n=5; overlapping lesion damage is depicted for one hemisphere, although actually four males had MN-POA/AH damage on the left side and one male had MN-POA/AH damage in the right hemisphere). Right panel: subjects with extensive lesion of mPOA/AH that included overlapping bilateral MN-POA/AH damage (n=8).

Fig. 2

Percentage of free trials in Y-maze tests during which ferrets chose to approach anesthetized male vs. female stimulus ferrets before (top panel) and after (bottom panel) the placement of electrolytic lesions in the medial preoptic area/anterior hypothalamus (POA/AH) of male subjects or of a sham operation in both sexes. Groups of males with brain lesions were distinguished by the presence of damage in the sexually dimorphic male nucleus of the POA/AH (MN-POA/AH); * p<0.05, ** p<0.01, *** p<0.001 vs. sham-operated females; ## p<0.01 vs. sham-operated males by Mann–Whitney post-hoc tests. The data are expressed as means±SEM. The number of subjects in each group is given in parentheses.

Fig. 3

Percentage of trials in Y-maze tests during which ferrets chose to approach male vs. female anal scent gland odorants before (top panel) and after (bottom panel) the placement of electrolytic lesions in the medial preoptic area/anterior hypothalamus (POA/AH) of male subjects or of a sham operation in both sexes. Groups of males with brain lesions were distinguished by the presence of damage in the sexually dimorphic male nucleus of the POA/AH (MN-POA/AH). * p<0.05, ** p<0.01, *** p<0.001 vs. sham-operated females by Mann–Whitney post-hoc tests. The data are expressed as means±SEM. The number of subjects in each group is given in parentheses.

Fig. 4

Percentage of trials in Y-maze tests during which ferrets chose to approach male vs. female urinary odorants before (top panel) and after (bottom panel) the placement of electrolytic lesions in the medial preoptic area/anterior hypothalamus (POA/AH) of male subjects or of a sham operation in both sexes. Groups of males with brain lesions were distinguished by the presence of damage in the sexually dimorphic male nucleus of the POA/AH (MN-POA/AH). * p<0.05, ** p<0.01, *** p<0.001 vs. sham-operated females by Mann–Whitney post-hoc tests. The data are expressed as means±SEM. The number of subjects in each group is given in parentheses.

Fig. 5

Effect of exposure to either soiled male or clean bedding on the number of Fos-immunoreactive cells present in different brain regions of male ferrets which had previously received electrolytic lesions of the medial preoptic area/anterior hypothalamus (POA/AH) or sham operations in both sexes. Groups of males with brain lesions were distinguished by the presence of damage in the sexually dimorphic male nucleus of the POA/AH (MN-POA/AH). The locations of the Fos counting regions (shaded areas) in the medial amygdala (MA), bed nucleus of the stria terminalis (BNST), medial preoptic area (mPOA), and ventromedial hypothalamus (VMH) are shown in the left panels. * p<0.05 soiled male vs. clean bedding effect in sham-operated females by an independent t-test. # p<0.05, ## p<0.01, ### p<0.001 comparisons with males that sustained bilateral MN-POA/AH damage by post-hoc LSD tests. The data are expressed as means±SEM, and the number of subjects in each group is given in parentheses. Black dots represent the individual subjects’ data points. Additional abbreviations: 3V — third ventricle, IC — internal capsule, OT — optic tract, LV — lateral ventricle, FX — fornix, AC — anterior commissure, OC — optic chiasm, ME — median eminence.

Fig. 6

Representative bright-field photomicrographs showing coronal ferret forebrain sections that were immunostained for Fos protein. Top row: medial amygdala sections from sham-operated females exposed to either clean (A) or soiled male (B) bedding. Middle row: medial preoptic area (mPOA) sections from sham-operated females exposed to either clean (C) or soiled male (D) bedding. Bottom row: mPOA sections from males that had sustained either a bilateral damage to the sexually dimorphic male nucleus of the preoptic area/anterior hypothalamus (E) or a sham operation (F) prior to exposure to soiled male bedding.