A vasopressin circuit that modulates mouse social investigation and anxiety-like behavior in a sex-specific manner.

One of the largest sex differences in brain neurochemistry is the expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate brain, with males having more AVP cells in the bed nucleus of the stria terminalis (BNST) than females. Despite the long-standing implication of AVP in social and anxiety-like behaviors, the circuitry underlying AVP's control of these behaviors is still not well defined. Using optogenetic approaches, we show that inhibiting AVP BNST cells reduces social investigation in males, but not in females, whereas stimulating these cells increases social investigation in both sexes, but more so in males. These cells may facilitate male social investigation through their projections to the lateral septum (LS), an area with the highest density of sexually differentiated AVP innervation in the brain, as optogenetic stimulation of BNST AVP → LS increased social investigation and anxiety-like behavior in males but not in females; the same stimulation also caused a biphasic response of LS cells ex vivo. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated all these responses. Together, these findings establish a sexually differentiated role for BNST AVP cells in the control of social investigation and anxiety-like behavior, likely mediated by their projections to the LS.

The Sensitivity and Specificity of Procalcitonin in Diagnosing Bacterial Sepsis in Neonates.

CONTEXT AND OBJECTIVES: Neonatal sepsis accounts for 15% of all neonatal deaths. Early detection enables prompt administration of antibiotic treatment, reducing morbidity and mortality. This study aims to review the sensitivity and specificity of procalcitonin in diagnosing microbiologically-proven sepsis in neonates to determine the optimal procalcitonin cut-off value for use in clinical practice. DATA SOURCES, STUDY SELECTION, AND DATA EXTRACTION: Medline, EMBASE and PubMed were searched on 3 May 2023 for original studies in symptomatic neonates in whom both blood culture and procalcitonin levels were taken, and a procalcitonin cut-off with either sensitivity or specificity reported. Studies that included asymptomatic or culture-negative neonates in the proven sepsis group were excluded. Risk of bias was assessed using the Qualitative Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: Nineteen original studies enrolling a total of 1920 symptomatic neonates (721 with proven sepsis) were included. Six studies used a procalcitonin cut-off of 0.5 ng/mL and found a sensitivity of 87% to 100% and specificity of 17% to 89%. Nine studies evaluated higher procalcitonin cut-off values between 0.99 ng/mL and 2 ng/mL, which were 67% to 98% sensitive and 41% to 89% specific. All other procalcitonin thresholds were neither sensitive nor specific. Meta-analysis was not performed because of high risk of bias within the identified studies. CONCLUSIONS: This review found that procalcitonin was highly sensitive (87% to 100%) at a cut-off value of 0.5 ng/mL, although specificity varied greatly across all cut-off values reviewed. The variation in diagnostic accuracy between studies suggests that procalcitonin may be useful to guide antibiotic cessation but should not be used alone as a diagnostic marker for neonatal sepsis.

A vasopressin circuit that modulates sex-specific social interest and anxiety-like behavior in mice.

One of the largest sex differences in brain neurochemistry is the male-biased expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate social brain. Despite the long-standing implication of AVP in social and anxiety-like behavior, the precise circuitry and anatomical substrate underlying its control are still poorly understood. By employing optogenetic manipulation of AVP cells within the bed nucleus of the stria terminalis (BNST), we have unveiled a central role for these cells in promoting social investigation, with a more pronounced role in males relative to females. These cells facilitate male social investigation and anxiety-like behavior through their projections to the lateral septum (LS), an area with the highest density of sexually-dimorphic AVP fibers. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated stimulation-mediated increases in these behaviors. Together, these findings establish a distinct BNST AVP → LS V1aR circuit that modulates sex-specific social interest and anxiety-like behavior.

Sex differences in vasopressin 1a receptor regulation of social communication within the lateral habenula and dorsal raphe of mice.

The neuropeptide arginine-vasopressin (AVP) has long been implicated in the regulation of social behavior and communication in diverse taxa, often through its actions on the V1a receptor (V1aR) and in a sex-different and steroid-dependent way. One source of sex-different brain AVP is the steroid-sensitive and sexually-dimorphic AVP neurons in the bed nucleus of the stria terminalis (BNST), a cell population that regulates social behavior in a sex-dependent manner. Potential targets of these BNST-AVP cells include the lateral habenula (LHb) and dorsal raphe (DR), areas known to be important for social behavior, yet few studies have investigated AVP action within these regions. Consequently, to test if V1aR action in the LHb or DR controls social behavior in a sexually dimorphic manner, we administered a highly-specific V1aR antagonist (or saline vehicle) in the LHb or DR of C57BL/6 male and female mice and tested its effects on social investigation, social communication (urine marking, ultrasonic vocalizations), and territorial aggression. V1aR antagonism of the LHb or DR decreased male urine marking toward unfamiliar males, but not toward unfamiliar females. Additionally, V1aR blockade of the LHb decreased ultrasonic vocalizations generated in the presence of females. Social investigation, locomotion and aggressive behavior were not altered by V1aR antagonism in either area. Blocking V1aR in the LHb or DR of females had no effect, indicating V1aR action in the DR and LHb drives sex differences in social communication.