PETRULIS - DE VRIES LAB
SEX-DIFFERENT EXPRESSION OF VASOPRESSIN
Removing sex-different vasopressin cells in bed nucleus of the stria terminalis (BNST) alters social behavior
In males only, selective lesions of BNST vasopressin (AVP) cells reduced social investigation of other males without altering ultrasonic vocalizations, aggression, copulation, anxiety, or investigation of females. In females, which have significantly fewer VP cells in the BNST, cell removal had minimal effects on social behavior and communication, indicating that these cells contribute to sex differences in social behavioral function. Similar effects were observed when AVP expression was knocked down in the BNST using RNA-interference. Increased social investigation of males by males can be driven by BNST AVP to lateral septum projections and depends on the vasopressin 1a receptor (see panel)


Removing sex-different vasopressin cells in bed nucleus of the stria terminalis (BNST) alters positive hedonic states and impairs recognition of social novelty
Circumstantial evidence supports the hypothesis that the sexually dimorphic vasopressin (VP) innervation of the brain tempers sickness behavior in males. Here we test this hypothesis directly, by comparing induced sickness behavior in animals with or without ablations of BNST VP cells, a major source of sexually dimorphic VP in the brain. Deletion of these cells had minimal effects on sickness behavior in males or female mice, but did increase consumption of sucrose (a measure of positive hedonic state) in both sexes. Males, but not females, with cell ablations showed impairment in recognition of social novelty compared to control mice. These data confirm that BNST VP cells control social behavior in a sexually dimorphic way, but do not play a critical role in sickness behavior.

Sex differences in both monosynaptic inputs and outputs of vasopressin cells in bed nucleus of the stria terminalis (BNST) and medial amygdala
Using modern viral mapping techniques, we identified sex differences in the monosynaptic inputs to BNST and medial amygdala AVP cells as well as confirming substantial sex differences in the outputs of these cells (shown: input density to different brain regions by sex; example of BNST AVP differences in innervation of lateral septum
HYPOTHALAMIC VASOPRESSIN
Removing vasopressin cells in the paraventricular nucleus of the hypothalamus (PVN) increases female social investigation and male anxiety
Deletion of PVN vasopressin (VP)-expressing cells increased social investigation in females, but not in males. However, in males but not in females, these lesions increased non-social anxiety-related behaviors in the elevated-plus maze. These results therefore point at differential involvement of PVN VP-expressing cells in the context of social and emotional behavior in the two sexes, which may contribute to sex differences in social communication and anxiety disorders.
We have also found that PVN VP ablation exacerbated sickness behavior in both sexes, but with a stronger effect on males. This suggests that PVN VP contributes to the change in motivated behaviors during sickness and may help promote recovery from infection (in press).

HYPOTHALAMIC VASOPRESSIN
Removing vasopressin cells from the suprachiasmatic nucleus of the hypothalamus (SCN) did not alter social and behavior, but increased anxiety-like behavior
