Oxytocin and Vasopressin Within the Ventral and Dorsal Lateral Septum Modulate Aggression in Female Rats

Overview

Journal Nat Commun

Specialty Biology

Date 2021 May 19

PMID 34006875

Citations 46

Authors

Vinicius Elias de Moura Oliveira

Michael Lukas

Hannah Nora Wolf

Elisa Durante

Alexandra Lorenz

Anna-Lena Mayer

Anna Bludau

Oliver J Bosch

Valery Grinevich

Veronica Egger

Trynke R de Jong

Inga D Neumann

Affiliations

Soon will be listed here.

Abstract

In contrast to male rats, aggression in virgin female rats has been rarely studied. Here, we established a rat model of enhanced aggression in females using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and arginine vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialysis approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), is required for aggression in female rats. Accordingly, increased activity of putative OXT receptor-positive neurons in the vLS, and decreased activity of putative AVP receptor-positive neurons in the dLS, are likely to underly aggression in female rats. Finally, in vitro activation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data suggest a model showing that septal release of OXT and AVP differentially affects aggression in females by modulating the inhibitory tone within LS sub-networks.

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References

Bosch O, Meddle S, Beiderbeck D, Douglas A, Neumann I . Brain oxytocin correlates with maternal aggression: link to anxiety. J Neurosci. 2005; 25(29):6807-15. PMC: 6725361. DOI: 10.1523/JNEUROSCI.1342-05.2005. View

Wong L, Wang L, DAmour J, Yumita T, Chen G, Yamaguchi T . Effective Modulation of Male Aggression through Lateral Septum to Medial Hypothalamus Projection. Curr Biol. 2016; 26(5):593-604. PMC: 4783202. DOI: 10.1016/j.cub.2015.12.065. View

Anpilov S, Shemesh Y, Eren N, Harony-Nicolas H, Benjamin A, Dine J . Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors. Neuron. 2020; 107(4):644-655.e7. PMC: 7447984. DOI: 10.1016/j.neuron.2020.05.028. View

Nephew B, Byrnes E, Bridges R . Vasopressin mediates enhanced offspring protection in multiparous rats. Neuropharmacology. 2009; 58(1):102-6. PMC: 2783294. DOI: 10.1016/j.neuropharm.2009.06.032. View

Nelson R, Trainor B . Neural mechanisms of aggression. Nat Rev Neurosci. 2007; 8(7):536-46. DOI: 10.1038/nrn2174. View

McDonald M, Markham C, Norvelle A, Elliott Albers H, Huhman K . GABAA receptor activation in the lateral septum reduces the expression of conditioned defeat and increases aggression in Syrian hamsters. Brain Res. 2012; 1439:27-33. PMC: 3273572. DOI: 10.1016/j.brainres.2011.12.042. View

Caughey S, Klampfl S, Bishop V, Pfoertsch J, Neumann I, Bosch O . Changes in the intensity of maternal aggression and central oxytocin and vasopressin V1a receptors across the peripartum period in the rat. J Neuroendocrinol. 2011; 23(11):1113-24. DOI: 10.1111/j.1365-2826.2011.02224.x. View

Widmer H, Ludwig M, Bancel F, Leng G, Dayanithi G . Neurosteroid regulation of oxytocin and vasopressin release from the rat supraoptic nucleus. J Physiol. 2003; 548(Pt 1):233-44. PMC: 2342803. DOI: 10.1113/jphysiol.2002.036863. View

Longair M, Baker D, Armstrong J . Simple Neurite Tracer: open source software for reconstruction, visualization and analysis of neuronal processes. Bioinformatics. 2011; 27(17):2453-4. DOI: 10.1093/bioinformatics/btr390. View

10.

Parker K, Oztan O, Libove R, Mohsin N, Karhson D, Sumiyoshi R . A randomized placebo-controlled pilot trial shows that intranasal vasopressin improves social deficits in children with autism. Sci Transl Med. 2019; 11(491). PMC: 6716148. DOI: 10.1126/scitranslmed.aau7356. View

11.

Leroy F, Park J, Asok A, Brann D, Meira T, Boyle L . A circuit from hippocampal CA2 to lateral septum disinhibits social aggression. Nature. 2018; 564(7735):213-218. PMC: 6364572. DOI: 10.1038/s41586-018-0772-0. View

12.

Lukas M, Neumann I . Social preference and maternal defeat-induced social avoidance in virgin female rats: sex differences in involvement of brain oxytocin and vasopressin. J Neurosci Methods. 2014; 234:101-7. DOI: 10.1016/j.jneumeth.2014.03.013. View

13.

Huber D, Veinante P, Stoop R . Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science. 2005; 308(5719):245-8. DOI: 10.1126/science.1105636. View

14.

Pfundmair M, Reinelt A, DeWall C, Feldmann L . Oxytocin strengthens the link between provocation and aggression among low anxiety people. Psychoneuroendocrinology. 2018; 93:124-132. DOI: 10.1016/j.psyneuen.2018.04.025. View

15.

DiBenedictis B, Nussbaum E, Cheung H, Veenema A . Quantitative mapping reveals age and sex differences in vasopressin, but not oxytocin, immunoreactivity in the rat social behavior neural network. J Comp Neurol. 2017; 525(11):2549-2570. PMC: 6066795. DOI: 10.1002/cne.24216. View

16.

Compaan J, Buijs R, Pool C, de Ruiter A, Koolhaas J . Differential lateral septal vasopressin innervation in aggressive and nonaggressive male mice. Brain Res Bull. 1993; 30(1-2):1-6. DOI: 10.1016/0361-9230(93)90032-7. View

17.

Oyegbile T, Marler C . Winning fights elevates testosterone levels in California mice and enhances future ability to win fights. Horm Behav. 2005; 48(3):259-67. DOI: 10.1016/j.yhbeh.2005.04.007. View

18.

Campbell A . Staying alive: evolution, culture, and women's intrasexual aggression. Behav Brain Sci. 2001; 22(2):203-14; discussion 214-52. DOI: 10.1017/s0140525x99001818. View

19.

Dumais K, Bredewold R, Mayer T, Veenema A . Sex differences in oxytocin receptor binding in forebrain regions: correlations with social interest in brain region- and sex- specific ways. Horm Behav. 2013; 64(4):693-701. DOI: 10.1016/j.yhbeh.2013.08.012. View

20.

Allaman-Exertier G, Reymond-Marron I, Tribollet E, Raggenbass M . Vasopressin modulates lateral septal network activity via two distinct electrophysiological mechanisms. Eur J Neurosci. 2007; 26(9):2633-42. DOI: 10.1111/j.1460-9568.2007.05866.x. View