Quantitative Cellular-resolution Map of the Oxytocin Receptor in Postnatally Developing Mouse Brains

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Apr 22

PMID 32313029

Citations 47

Authors

Kyra T Newmaster

Zachary T Nolan

Uree Chon

Daniel J Vanselow

Abigael R Weit

Manal Tabbaa

Shizu Hidema

Katsuhiko Nishimori

Elizabeth A D Hammock

Yongsoo Kim

Affiliations

Soon will be listed here.

Abstract

The oxytocin receptor (OTR) plays critical roles in social behavior development. Despite its significance, brain-wide quantitative understanding of OTR expression remains limited in postnatally developing brains. Here, we develop postnatal 3D template brains to register whole brain images with cellular resolution to systematically quantify OTR cell densities. We utilize fluorescent reporter mice (Otr) and find that cortical regions show temporally and spatially heterogeneous patterns with transient postnatal OTR expression without cell death. Cortical OTR cells are largely glutamatergic neurons with the exception of cells in layer 6b. Subcortical regions show similar temporal regulation except the hypothalamus and two hypothalamic nuclei display sexually dimorphic OTR expression. Lack of OTR expression correlates with reduced dendritic spine densities in selected cortical regions of developing brains. Lastly, we create a website to visualize our high-resolution imaging data. In summary, our research provides a comprehensive resource for postnatal OTR expression in the mouse brain.

Citing Articles

The Dynamicity of the Oxytocin Receptor in the Brain May Trigger Sensory Deficits in Autism Spectrum Disorder.

Camerino C Curr Issues Mol Biol. 2025; 47(1).

PMID: 39852176 PMC: 11763978. DOI: 10.3390/cimb47010061.

Differential temporal decline of cerebral oxytocin and μ-opioid receptor density during the aging process in mice.

Effah F, Nidadavolu P, de Gusmao Taveiros Silva N, Wojtowicz M, Camarini R, Zimmer A Eur J Neurosci. 2024; 60(11):6686-6703.

PMID: 39435722 PMC: 11612844. DOI: 10.1111/ejn.16578.

Developmental mouse brain common coordinate framework.

Kronman F, Liwang J, Betty R, Vanselow D, Wu Y, Tustison N Nat Commun. 2024; 15(1):9072.

PMID: 39433760 PMC: 11494176. DOI: 10.1038/s41467-024-53254-w.

Isolated during adolescence: long-term impact on social behavior, pain sensitivity, and the oxytocin system in male and female rats.

P Graf A, Hansson A, Spanagel R Biol Sex Differ. 2024; 15(1):78.

PMID: 39407302 PMC: 11476712. DOI: 10.1186/s13293-024-00655-7.

Selective vulnerability of parvocellular oxytocin neurons in social dysfunction.

Tsurutani M, Goto T, Hagihara M, Irie S, Miyamichi K Nat Commun. 2024; 15(1):8661.

PMID: 39370447 PMC: 11456597. DOI: 10.1038/s41467-024-53092-w.

References

Southwell D, Paredes M, Galvao R, Jones D, Froemke R, Sebe J . Intrinsically determined cell death of developing cortical interneurons. Nature. 2012; 491(7422):109-13. PMC: 3726009. DOI: 10.1038/nature11523. View

Theodosis D, Koksma J, Trailin A, Langle S, Piet R, Lodder J . Oxytocin and estrogen promote rapid formation of functional GABA synapses in the adult supraoptic nucleus. Mol Cell Neurosci. 2006; 31(4):785-94. DOI: 10.1016/j.mcn.2006.01.006. View

Bakos J, Srancikova A, Havranek T, Bacova Z . Molecular Mechanisms of Oxytocin Signaling at the Synaptic Connection. Neural Plast. 2018; 2018:4864107. PMC: 6051047. DOI: 10.1155/2018/4864107. View

Nakajima M, Gorlich A, Heintz N . Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons. Cell. 2014; 159(2):295-305. PMC: 4206218. DOI: 10.1016/j.cell.2014.09.020. View

Veinante P, Freund-Mercier M . Distribution of oxytocin- and vasopressin-binding sites in the rat extended amygdala: a histoautoradiographic study. J Comp Neurol. 1997; 383(3):305-25. View

Blitzer D, Wells T, Hawley W . Administration of an oxytocin receptor antagonist attenuates sexual motivation in male rats. Horm Behav. 2017; 94:33-39. DOI: 10.1016/j.yhbeh.2017.06.002. View

Oh S, Harris J, Ng L, Winslow B, Cain N, Mihalas S . A mesoscale connectome of the mouse brain. Nature. 2014; 508(7495):207-14. PMC: 5102064. DOI: 10.1038/nature13186. View

Jurek B, Neumann I . The Oxytocin Receptor: From Intracellular Signaling to Behavior. Physiol Rev. 2018; 98(3):1805-1908. DOI: 10.1152/physrev.00031.2017. View

Dumais K, Veenema A . Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior. Front Neuroendocrinol. 2015; 40:1-23. PMC: 4633405. DOI: 10.1016/j.yfrne.2015.04.003. View

10.

Bienkowski M, Bowman I, Song M, Gou L, Ard T, Cotter K . Integration of gene expression and brain-wide connectivity reveals the multiscale organization of mouse hippocampal networks. Nat Neurosci. 2018; 21(11):1628-1643. PMC: 6398347. DOI: 10.1038/s41593-018-0241-y. View

11.

Li K, Nakajima M, Ibanez-Tallon I, Heintz N . A Cortical Circuit for Sexually Dimorphic Oxytocin-Dependent Anxiety Behaviors. Cell. 2016; 167(1):60-72.e11. PMC: 5220951. DOI: 10.1016/j.cell.2016.08.067. View

12.

Stoop R . Neuromodulation by oxytocin and vasopressin. Neuron. 2012; 76(1):142-59. DOI: 10.1016/j.neuron.2012.09.025. View

13.

Pobbe R, Pearson B, Defensor E, Bolivar V, Young 3rd W, Lee H . Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors. Horm Behav. 2011; 61(3):436-44. PMC: 3373312. DOI: 10.1016/j.yhbeh.2011.10.010. View

14.

Klein S, Staring M, Murphy K, Viergever M, Pluim J . elastix: a toolbox for intensity-based medical image registration. IEEE Trans Med Imaging. 2009; 29(1):196-205. DOI: 10.1109/TMI.2009.2035616. View

15.

Hammock E, Levitt P . Oxytocin receptor ligand binding in embryonic tissue and postnatal brain development of the C57BL/6J mouse. Front Behav Neurosci. 2013; 7:195. PMC: 3858721. DOI: 10.3389/fnbeh.2013.00195. View

16.

Lin Y, Hsieh T, Tsai T, Chen C, Huang C, Hsu K . Conditional Deletion of Hippocampal CA2/CA3a Oxytocin Receptors Impairs the Persistence of Long-Term Social Recognition Memory in Mice. J Neurosci. 2017; 38(5):1218-1231. PMC: 6596267. DOI: 10.1523/JNEUROSCI.1896-17.2017. View

17.

Alves E, Fielder A, Ghabriel N, Sawyer M, Buisman-Pijlman F . Early social environment affects the endogenous oxytocin system: a review and future directions. Front Endocrinol (Lausanne). 2015; 6:32. PMC: 4356154. DOI: 10.3389/fendo.2015.00032. View

18.

Kim Y, Yang G, Pradhan K, Venkataraju K, Bota M, Garcia Del Molino L . Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism. Cell. 2017; 171(2):456-469.e22. PMC: 5870827. DOI: 10.1016/j.cell.2017.09.020. View

19.

Bayram-Weston Z, Olsen E, Harrison D, Dunnett S, Brooks S . Optimising Golgi-Cox staining for use with perfusion-fixed brain tissue validated in the zQ175 mouse model of Huntington's disease. J Neurosci Methods. 2015; 265:81-8. PMC: 4863524. DOI: 10.1016/j.jneumeth.2015.09.033. View

20.

Sunkin S, Ng L, Lau C, Dolbeare T, Gilbert T, Thompson C . Allen Brain Atlas: an integrated spatio-temporal portal for exploring the central nervous system. Nucleic Acids Res. 2012; 41(Database issue):D996-D1008. PMC: 3531093. DOI: 10.1093/nar/gks1042. View