Mice Lacking Acid-sensing Ion Channel 2 in the Medial Prefrontal Cortex Exhibit Social Dominance

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Oct 25

PMID 39453995

Authors

Boren Lin

Zhen Jin

Gyeongah Park

Qian Ge

Kritika Singh

William G Ryan V

Ali Sajid Imami

Farzaneh Naghavi

Olivia Ann Miller

Saira Khan

Hui Lu

Robert E McCullumsmith

Jianyang Du

Affiliations

Soon will be listed here.

Abstract

Social dominance is essential for maintaining a stable society and has both positive and negative impacts on social animals, including humans. However, the regulatory mechanisms governing social dominance, as well as the crucial regulators and biomarkers involved, remain poorly understood. We discover that mice lacking acid-sensing ion channel 2 (ASIC2) exhibit persistently higher social dominance than their wild-type cagemates. Conversely, overexpression of ASIC2 in the medial prefrontal cortex reverses the dominance hierarchy observed in ASIC2 knockout () mice. neurons exhibit increased synaptic transmission and plasticity, potentially mediated by protein kinase A signaling pathway. Furthermore, ASIC2 plays distinct functional roles in excitatory and inhibitory neurons, thereby modulating the balance of neuronal activities underlying social dominance behaviors-a phenomenon suggestive of a cell subtype-specific mechanism. This research lays the groundwork for understanding the mechanisms of social dominance, offering potential insights for managing social disorders, such as depression and anxiety.

References

Zhou T, Zhu H, Fan Z, Wang F, Chen Y, Liang H . History of winning remodels thalamo-PFC circuit to reinforce social dominance. Science. 2017; 357(6347):162-168. DOI: 10.1126/science.aak9726. View

Wang F, Zhu J, Zhu H, Zhang Q, Lin Z, Hu H . Bidirectional control of social hierarchy by synaptic efficacy in medial prefrontal cortex. Science. 2011; 334(6056):693-7. DOI: 10.1126/science.1209951. View

Ferreira-Fernandes E, Peca J . The Neural Circuit Architecture of Social Hierarchy in Rodents and Primates. Front Cell Neurosci. 2022; 16:874310. PMC: 9133341. DOI: 10.3389/fncel.2022.874310. View

Borodinsky L, Spitzer N . Second messenger pas de deux: the coordinated dance between calcium and cAMP. Sci STKE. 2006; 2006(336):pe22. DOI: 10.1126/stke.3362006pe22. View

Fan Z, Zhu H, Zhou T, Wang S, Wu Y, Hu H . Using the tube test to measure social hierarchy in mice. Nat Protoc. 2019; 14(3):819-831. DOI: 10.1038/s41596-018-0116-4. View

Quevedo J, Vianna M, Martins M, Barichello T, Medina J, Roesler R . Protein synthesis, PKA, and MAP kinase are differentially involved in short- and long-term memory in rats. Behav Brain Res. 2004; 154(2):339-43. DOI: 10.1016/j.bbr.2004.03.001. View

Wright W, Graziane N, Neumann P, Hamilton P, Cates H, Fuerst L . Silent synapses dictate cocaine memory destabilization and reconsolidation. Nat Neurosci. 2019; 23(1):32-46. PMC: 6930359. DOI: 10.1038/s41593-019-0537-6. View

Amodio D, Frith C . Meeting of minds: the medial frontal cortex and social cognition. Nat Rev Neurosci. 2006; 7(4):268-77. DOI: 10.1038/nrn1884. View

Wang Q, Wang Q, Song X, Jiang Q, Wu Y, Li Y . Fear extinction requires ASIC1a-dependent regulation of hippocampal-prefrontal correlates. Sci Adv. 2018; 4(10):eaau3075. PMC: 6223961. DOI: 10.1126/sciadv.aau3075. View

10.

Rein B, Ma K, Yan Z . A standardized social preference protocol for measuring social deficits in mouse models of autism. Nat Protoc. 2020; 15(10):3464-3477. PMC: 8103520. DOI: 10.1038/s41596-020-0382-9. View

11.

Bruce J, Straub S, Yule D . Crosstalk between cAMP and Ca2+ signaling in non-excitable cells. Cell Calcium. 2003; 34(6):431-44. DOI: 10.1016/s0143-4160(03)00150-7. View

12.

Storozhuk M, Kondratskaya E, Nikolaenko L, Krishtal O . A modulatory role of ASICs on GABAergic synapses in rat hippocampal cell cultures. Mol Brain. 2016; 9(1):90. PMC: 5070181. DOI: 10.1186/s13041-016-0269-4. View

13.

Du J, Reznikov L, Price M, Zha X, Lu Y, Moninger T . Protons are a neurotransmitter that regulates synaptic plasticity in the lateral amygdala. Proc Natl Acad Sci U S A. 2014; 111(24):8961-6. PMC: 4066526. DOI: 10.1073/pnas.1407018111. View

14.

Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M . A proton-gated cation channel involved in acid-sensing. Nature. 1997; 386(6621):173-7. DOI: 10.1038/386173a0. View

15.

Berridge M . The interaction of cyclic nucleotides and calcium in the control of cellular activity. Adv Cyclic Nucleotide Res. 1975; 6:1-98. View

16.

Creeden J, Kipp Z, Xu M, Flight R, Moseley H, Martinez G . Hepatic kinome atlas: An in-depth identification of kinase pathways in liver fibrosis of humans and rodents. Hepatology. 2022; 76(5):1376-1388. PMC: 9489820. DOI: 10.1002/hep.32467. View

17.

Cull-Candy S, Kelly L, Farrant M . Regulation of Ca2+-permeable AMPA receptors: synaptic plasticity and beyond. Curr Opin Neurobiol. 2006; 16(3):288-97. DOI: 10.1016/j.conb.2006.05.012. View

18.

Barad M, Bourtchouladze R, Winder D, Golan H, Kandel E . Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory. Proc Natl Acad Sci U S A. 1998; 95(25):15020-5. PMC: 24568. DOI: 10.1073/pnas.95.25.15020. View

19.

Rietveld L, Stuss D, McPhee D, Delaney K . Genotype-specific effects of Mecp2 loss-of-function on morphology of Layer V pyramidal neurons in heterozygous female Rett syndrome model mice. Front Cell Neurosci. 2015; 9:145. PMC: 4403522. DOI: 10.3389/fncel.2015.00145. View

20.

Guo Z, Yin L, Diaz V, Dai B, Osakada T, Lischinsky J . Neural dynamics in the limbic system during male social behaviors. Neuron. 2023; 111(20):3288-3306.e4. PMC: 10592239. DOI: 10.1016/j.neuron.2023.07.011. View