A Vasopressin Circuit That Modulates Sex-specific Social Interest and Anxiety-like Behavior in Mice

Overview

Journal bioRxiv

Date 2023 Nov 21

PMID 37986987

Authors

Nicole Rigney

Elba Campos-Lira

Matthew K Kirchner

Wei Wei

Selma Belkasim

Rachael Beaumont

Sumeet Singh

Geert J de Vries

Aras Petrulis

Affiliations

Soon will be listed here.

Abstract

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.

References

Manning M, Misicka A, Olma A, Bankowski K, Stoev S, Chini B . Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics. J Neuroendocrinol. 2012; 24(4):609-28. PMC: 3490377. DOI: 10.1111/j.1365-2826.2012.02303.x. View

Oztan O, Garner J, Constantino J, Parker K . Neonatal CSF vasopressin concentration predicts later medical record diagnoses of autism spectrum disorder. Proc Natl Acad Sci U S A. 2020; 117(19):10609-10613. PMC: 7229671. DOI: 10.1073/pnas.1919050117. View

Rigney N, de Vries G, Petrulis A . Sex differences in afferents and efferents of vasopressin neurons of the bed nucleus of the stria terminalis and medial amygdala in mice. Horm Behav. 2023; 154:105407. PMC: 10529859. DOI: 10.1016/j.yhbeh.2023.105407. View

Engelmann M, Wotjak C, Neumann I, Ludwig M, Landgraf R . Behavioral consequences of intracerebral vasopressin and oxytocin: focus on learning and memory. Neurosci Biobehav Rev. 1996; 20(3):341-58. DOI: 10.1016/0149-7634(95)00059-3. View

Whylings J, Rigney N, de Vries G, Petrulis A . Reduction in vasopressin cells in the suprachiasmatic nucleus in mice increases anxiety and alters fluid intake. Horm Behav. 2021; 133:104997. PMC: 8529700. DOI: 10.1016/j.yhbeh.2021.104997. View

Dao N, Brockway D, Crowley N . In Vitro Optogenetic Characterization of Neuropeptide Release from Prefrontal Cortical Somatostatin Neurons. Neuroscience. 2019; 419:1-4. DOI: 10.1016/j.neuroscience.2019.08.014. View

Oliveira V, Lukas M, Wolf H, Durante E, Lorenz A, Mayer A . Oxytocin and vasopressin within the ventral and dorsal lateral septum modulate aggression in female rats. Nat Commun. 2021; 12(1):2900. PMC: 8131389. DOI: 10.1038/s41467-021-23064-5. View

Whylings J, Rigney N, Peters N, de Vries G, Petrulis A . Sexually dimorphic role of BNST vasopressin cells in sickness and social behavior in male and female mice. Brain Behav Immun. 2019; 83:68-77. PMC: 6906230. DOI: 10.1016/j.bbi.2019.09.015. View

Oldfield R, Harris R, Hofmann H . Integrating resource defence theory with a neural nonapeptide pathway to explain territory-based mating systems. Front Zool. 2016; 12 Suppl 1:S16. PMC: 4722349. DOI: 10.1186/1742-9994-12-S1-S16. View

10.

Bredewold R, Veenema A . Sex differences in the regulation of social and anxiety-related behaviors: insights from vasopressin and oxytocin brain systems. Curr Opin Neurobiol. 2018; 49:132-140. PMC: 6055524. DOI: 10.1016/j.conb.2018.02.011. View

11.

Insel T . The challenge of translation in social neuroscience: a review of oxytocin, vasopressin, and affiliative behavior. Neuron. 2010; 65(6):768-79. PMC: 2847497. DOI: 10.1016/j.neuron.2010.03.005. View

12.

Raggenbass M, Dubois-Dauphin M, Tribollet E, Dreifuss J . Direct excitatory action of vasopressin in the lateral septum of the rat brain. Brain Res. 1988; 459(1):60-9. DOI: 10.1016/0006-8993(88)90286-7. View

13.

Duque-Wilckens N, Steinman M, Laredo S, Hao R, Perkeybile A, Bales K . Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects. Neuropharmacology. 2016; 110(Pt A):59-68. PMC: 5028294. DOI: 10.1016/j.neuropharm.2016.07.018. View

14.

Bielsky I, Hu S, Young L . Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice. Behav Brain Res. 2005; 164(1):132-6. DOI: 10.1016/j.bbr.2005.06.005. View

15.

Moncho-Bogani J, Lanuza E, Hernandez A, Novejarque A, Martinez-Garcia F . Attractive properties of sexual pheromones in mice: innate or learned?. Physiol Behav. 2002; 77(1):167-76. DOI: 10.1016/s0031-9384(02)00842-9. View

16.

Caldwell H, Lee H, Macbeth A, Young 3rd W . Vasopressin: behavioral roles of an "original" neuropeptide. Prog Neurobiol. 2007; 84(1):1-24. PMC: 2292122. DOI: 10.1016/j.pneurobio.2007.10.007. View

17.

Neumann I, Landgraf R . Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors. Trends Neurosci. 2012; 35(11):649-59. DOI: 10.1016/j.tins.2012.08.004. View

18.

Arakawa H, Blanchard D, Arakawa K, Dunlap C, Blanchard R . Scent marking behavior as an odorant communication in mice. Neurosci Biobehav Rev. 2008; 32(7):1236-48. PMC: 2577770. DOI: 10.1016/j.neubiorev.2008.05.012. View

19.

Warburton V, Sales G, Milligan S . The emission and elicitation of mouse ultrasonic vocalizations: the effects of age, sex and gonadal status. Physiol Behav. 1989; 45(1):41-7. DOI: 10.1016/0031-9384(89)90164-9. View

20.

Scott N, Prigge M, Yizhar O, Kimchi T . A sexually dimorphic hypothalamic circuit controls maternal care and oxytocin secretion. Nature. 2015; 525(7570):519-22. DOI: 10.1038/nature15378. View