Vasopressin cell groups exhibit strongly divergent responses to copulation and male-male interactions in mice

Abstract

Arginine vasopressin (AVP) and its nonmammalian homolog arginine vasotocin influence social behaviors ranging from affiliation to resident-intruder aggression. Although numerous sites of action have been established for these behavioral effects, the involvement of specific AVP cell groups in the brain is poorly understood, and socially elicited Fos responses have not been quantified for many of the AVP cell groups found in rodents. Surprisingly, this includes the AVP population in the posterior part of the medial bed nucleus of the stria terminalis (BSTMP), which has been extensively implicated, albeit indirectly, in various aspects of affiliation and other social behaviors. We examined the Fos responses of eight hypothalamic and three extra-hypothalamic AVP-immunoreactive (-ir) cell groups to copulation, nonaggressive male-male interaction, and aggressive male-male interaction in both dominant and subordinate C57BL/6J mice. The BSTMP cells exhibited a response profile that was unlike all other cell groups: from a control baseline of approximately 5% of AVP-ir neurons colocalizing with Fos, colocalization increased significantly to approximately 12% following nonaggressive male-male interaction, and to approximately 70% following copulation. Aggressive interactions did not increase colocalization beyond the level observed in nonaggressive male mice. These results suggest that BSTMP neurons in mice may increase AVP-Fos colocalization selectively in response to affiliation-related stimuli, similar to findings in finches. In contrast, virtually all other cell groups were responsive to negative aspects of interaction, either through elevated AVP-Fos colocalization in subordinate animals, positive correlations of AVP-Fos colocalization with bites received, and/or negative correlations of AVP-Fos colocalization with dominance. These findings greatly expand what is known of the contributions of specific brain AVP cell groups to social behavior.

Fig. 1

Photomicrographs showing the position and morphology of AVP-ir neurons in the posterior part of the medial bed nucleus of the stria terminalis (BSTMP; A, B) and ventral BSTM (BSTMV; C, D). Medial is to the right in all photos. The box in panel A shows an area expressing a high density of AVP-ir neurons. Panel B shows AVP-ir neurons from the same animal at a higher magnification, and the asterisk in panel C corresponds to the position of the asterisk in panel D. The AVP-ir neurons in the BSTMP are small, round, and weakly immunoreactive (also see Figs. 3A–C), whereas those in the BSTMV are larger, variably shaped, and strongly immunoreactive. All photos were taken at a rostrocaudal level comparable to plate 32 of the mouse brain atlas. Scale bars=100 μm in panels A and C; 25 μm in panel B; and 50 μm in panel D. Abbreviations: ac, anterior commissure; f, fornix; ic, internal capsule.

Fig. 2

Photomicrographs showing the position and morphology of AVP-ir neurons in the preoptic area (POA) and hypothalamus: (A) anterior commissural nucleus (AC; caudoventral to the anterior commissure, and thus caudoventral to the photo in Fig. 1C); (B) POA, anterior hypothalamic area (AH) and supraoptic nucleus (SON); (C) nucleus circularis (NC) and suprachiasmatic nucleus (SCN); (D) tuberal region of the lateral hypothalamus (tuberal LH) and retrochiasmatic SON (rSON); and (E) caudal paraventricular nucleus (PVN). Medial is to the right in all photos except panel E, where medial is to the left. Rostrocaudal levels of these photos correspond, respectively, to plates 33, 36, 37, 39 and 38 of the mouse brain atlas. All scale bars=100 μm. Other abbreviations: hht, hypothalamo-hypophyseal tract; ot, optic tract; v, 3rd ventricle.

Fig. 3

Representative colocalization of AVP (Alexa Fluor 488; green) and Fos (Alexa Fluor 594; red) in the posterior part of the medial bed nucleus of the stria terminalis (BSTMP; A–C) and paraventricular nucleus (D) following copulation. Scale bars=25 μm.

Fig. 4

AVP-ir neurons in the posterior part of the medial bed nucleus of the stria terminalis (BSTMP) exhibit robust Fos responses to copulation (A) and comparatively modest responses to nonaggressive chemoinvestigation (B). Aggressive interactions produce no increase in colocalization above the levels observed in nonaggressive males that chemoinvestigated (note also that AVP-Fos colocalization in the BSTMP correlates with measures of sexual behavior, but not aggression; see Tables 2 and 4). The data shown in both panels are for the caudal portion of the cell group only; similar patterns were found rostrally but were only significant in the copulation study (Table 1). Data are shown as means± SEM and n’s per group are indicated in the bars. Different letters above the error bars denote significant group differences (Fisher PLSD p<0.05 following significant ANOVA).

Fig. 5

AVP-ir neurons of the AH, BSTMV, POA, caudal PVN, SON, and tuberal LH exhibit response profiles that suggest a sensitivity to stressful or negative aspects of social interaction. AVP-Fos colocalization in these areas is greater in subordinate animals relative to dominant animals (A, B), positively correlated with bites received (C–G), or negatively correlated with dominance index (bites given minus bites received; H–J). Data in panels A and B are shown as means±SEM and n’s per group are indicated in the bars. Different letters above the error bars denote significant group differences (Fisher PLSD p<0.05 following significant ANOVA). Abbreviations as in Figs. 1 and 2. Additional data are provided in Tables 3 and 4.