# Social Processing in the Amygdala: Single-Nucleus RNA-Sequencing Reveals Distinct Neuronal Responses to Dominant and Subordinate Cues

**Authors:** Madeleine F. Dwortz, Hans A. Hofmann, James P. Curley

PMC · DOI: 10.21203/rs.3.rs-8564517/v1 · Research Square · 2026-02-10

## TL;DR

This study uses RNA sequencing to identify specific neurons in the mouse amygdala that respond differently to social dominance and subordinate cues.

## Contribution

The study reveals distinct glutamatergic and GABAergic neuronal responses to social olfactory cues in the amygdala using snRNA-seq.

## Key findings

- A glutamatergic cluster aligned with Slc17a7 (VGLUT1) medial amygdala neurons responds preferentially to dominant cues.
- A larger glutamatergic Slc17a6 (VGLUT2) cluster responds more to subordinate cues, highlighting the medial amygdala's role in social olfactory processing.
- A GABAergic cluster with elevated Drd2 expression responds to dominant cues, linking dopamine receptor 2 to threat responses.

## Abstract

The amygdala serves as a critical neural hub for interpreting social cues, with its distinct subregions and diverse neuronal populations playing specialized roles in processing these signals. Here, we employ single-nucleus RNA sequencing (snRNA-seq) to characterize neuronal responses in the mouse amygdala to olfactory cues associated with social dominance, uncovering distinct activation patterns within glutamatergic and GABAergic populations. We find that a glutamatergic cluster closely aligned with Slc17a7 (VGLUT1) medial amygdala (MeA) neurons preferentially responds to dominant cues. In contrast, a larger glutamatergic Slc17a6 (VGLUT2) cluster associated with MeA, cortical, and basomedial amygdala neurons exhibits a heightened response to subordinate cues, underscoring the MeA’s role in processing social olfactory information. Additionally, a glutamatergic cluster resembling dorsal endopiriform (EPd) neurons responds more strongly to dominant stimuli, supporting the EPd’s role in olfactory perception. We also identify a GABAergic cluster with elevated dopamine receptor 2 (Drd2) expression that predominantly responds to dominant cues, consistent with this receptor’s role in mediating threat responses. Finally, gene co-expression network analysis links cluster-specific gene expression to distinct biological processes. Together, these findings reveal neuronal and molecular mechanisms underlying social processing of dominance-related olfactory signals, enhancing our understanding of the neural substrates of social behavior.

## Linked entities

- **Genes:** SLC17A7 (solute carrier family 17 member 7) [NCBI Gene 57030], SLC17A7 (solute carrier family 17 member 7) [NCBI Gene 57030], SLC17A6 (solute carrier family 17 member 6) [NCBI Gene 57084], SLC17A6 (solute carrier family 17 member 6) [NCBI Gene 57084], DRD2 (dopamine receptor D2) [NCBI Gene 1813]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Baz1a (bromodomain adjacent to zinc finger domain 1A) [NCBI Gene 217578] {aka Acf1, B930060C03, Gtl5, Wcrf180, cbp146}, Per2 (period circadian clock 2) [NCBI Gene 18627] {aka mKIAA0347, mPer2}, Pim1 (Pim1, proto-oncogene, serine/threonine kinase) [NCBI Gene 18712] {aka Pim-1}, Hba-a1 (hemoglobin alpha, adult chain 1) [NCBI Gene 15122] {aka Hba, Hba1, Hbat1}, Sertad1 (SERTA domain containing 1) [NCBI Gene 55942] {aka 1110032C13Rik, Sei-1, Sei1, TRIP-Br1}, Tiparp (TCDD-inducible poly(ADP-ribose) polymerase) [NCBI Gene 99929] {aka ARTD14, PARP7}, Pdyn (prodynorphin) [NCBI Gene 18610] {aka Dyn}, Slc17a6 (solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6) [NCBI Gene 140919] {aka 2900073D12Rik, DNPI, VGLUT2}, Mest (mesoderm specific transcript) [NCBI Gene 17294] {aka Peg1}, Btg2 (BTG anti-proliferation factor 2) [NCBI Gene 12227] {aka APRO1, Pc3, TIS21}, Avpr1b (arginine vasopressin receptor 1B) [NCBI Gene 26361] {aka AVPR V1b, AVPR V3, AVPR3, V3/V1b, VIBR, VPR3}, ALDH7A1 (aldehyde dehydrogenase 7 family member A1) [NCBI Gene 501] {aka ATQ1, EPD, EPEO4, PDE}, Nr4a3 (nuclear receptor subfamily 4, group A, member 3) [NCBI Gene 18124] {aka CHN, CSMF, MINOR, NOR-1, Nor1, TEC}, Nr4a2 (nuclear receptor subfamily 4, group A, member 2) [NCBI Gene 18227] {aka HZF-3, NOT, Nurr1, RNR-1, TINOR, TINUR}, Slc1a3 (solute carrier family 1 (glial high affinity glutamate transporter), member 3) [NCBI Gene 20512] {aka B430115D02Rik, Eaat1, GLAST, GLAST-1, GLU-T, GluT-1}, Ier2 (immediate early response 2) [NCBI Gene 15936] {aka Ch1, Pip92}, Barhl2 (BarH like homeobox 2) [NCBI Gene 104382] {aka E130309B19Rik, MBH1}, Egr4 (early growth response 4) [NCBI Gene 13656] {aka NGF1-C, NGFI-C, NGFIC, pAT133}, Pde7b (phosphodiesterase 7B) [NCBI Gene 29863], Tnfaip6 (tumor necrosis factor alpha induced protein 6) [NCBI Gene 21930] {aka TSG-6, Tnfip6, Tsg6}, Sik1 (salt inducible kinase 1) [NCBI Gene 17691] {aka Hrt-20, Msk, Sik, Sik-1, Snf1lk}, Gadd45g (growth arrest and DNA-damage-inducible 45 gamma) [NCBI Gene 23882] {aka CR6, DDIT2, OIG37}, Slc32a1 (solute carrier family 32 (GABA vesicular transporter), member 1) [NCBI Gene 22348] {aka VGAT, Viaat}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Rnd3 (Rho family GTPase 3) [NCBI Gene 74194] {aka 2610017M01Rik, Arhe, Rhoe}, Fosl2 (fos-like antigen 2) [NCBI Gene 14284] {aka Fra-2}, Lrrk2 (leucine-rich repeat kinase 2) [NCBI Gene 66725] {aka 4921513O20Rik, 9330188B09Rik, D630001M17Rik, Gm927, cI-46}, Six3 (sine oculis-related homeobox 3) [NCBI Gene 20473] {aka E130112M24Rik, Six3a, Six3alpha, Six3b, Six3beta}, Dusp1 (dual specificity phosphatase 1) [NCBI Gene 19252] {aka 3CH134, MKP1, Ptpn16, erp, mkp-1}, Egr1 (early growth response 1) [NCBI Gene 13653] {aka A530045N19Rik, ETR103, Egr-1, Krox-1, Krox-24, Krox24}, Tns1 (tensin 1) [NCBI Gene 21961] {aka 1110018I21Rik, 1200014E20Rik, E030018G17Rik, E030037J05Rik, Tns}, Pim3 (Pim3, proto-oncogene, serine/threonine kinase) [NCBI Gene 223775] {aka Kid1}, Oxt (oxytocin) [NCBI Gene 18429] {aka OT, Oxy}, Dnajb5 (DnaJ heat shock protein family (Hsp40) member B5) [NCBI Gene 56323] {aka 1110058L06Rik, Hsc40, Hsp40-3}, Ccnl1 (cyclin L1) [NCBI Gene 56706] {aka 2610030E23Rik, Ccnl, ania-6a}, Coq10b (coenzyme Q10B) [NCBI Gene 67876] {aka 1500041J02Rik, 1700030I21Rik, 9530077A17Rik}, Fos (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14281] {aka D12Rfj1, c-fos, cFos}, Plk2 (polo like kinase 2) [NCBI Gene 20620] {aka Snk}, Sp9 (trans-acting transcription factor 9) [NCBI Gene 381373], Junb (jun B proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16477], Trib1 (tribbles pseudokinase 1) [NCBI Gene 211770] {aka A530090O15Rik, TRB-1, Trb1}, Malat1 (metastasis associated lung adenocarcinoma transcript 1 (non-coding RNA)) [NCBI Gene 72289] {aka 2210401K01Rik, 9430072K23Rik, Neat2}, Drd1 (dopamine receptor D1) [NCBI Gene 13488] {aka C030036C15Rik, Drd-1, Drd1a, Gpcr15}, Peli1 (pellino 1) [NCBI Gene 67245] {aka 2810468L03Rik, A930031K15Rik, D11Ertd676e}, Drd2 (dopamine receptor D2) [NCBI Gene 13489] {aka D2R, Drd-2}, Homer1 (homer scaffolding protein 1) [NCBI Gene 26556] {aka PSD-Zip45, SYN47, Ves-1, homer-1, vesl-1}, Midn (midnolin) [NCBI Gene 59090] {aka 3000003C15Rik}, Sst (somatostatin) [NCBI Gene 20604] {aka SOM, SRIF, SS, Smst}, Pde10a (phosphodiesterase 10A) [NCBI Gene 23984], Csrnp1 (cysteine-serine-rich nuclear protein 1) [NCBI Gene 215418] {aka 4931429D10Rik, Axud1, CSRNP-1, URAX1, taip-3}, Nr4a1 (nuclear receptor subfamily 4, group A, member 1) [NCBI Gene 15370] {aka GFRP1, Gfrp, Hbr-1, Hbr1, Hmr, N10}, DRD2 (dopamine receptor D2) [NCBI Gene 1813] {aka D2DR, D2R}, Ccdc42 (coiled-coil domain containing 42) [NCBI Gene 276920] {aka A530001H01Rik}, Fosb (Fos B proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 14282], Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Plat (plasminogen activator, tissue) [NCBI Gene 18791] {aka D8Ertd2e, tPA}, Avp (arginine vasopressin) [NCBI Gene 11998] {aka Vp, Vsp}, Cyp26b1 (cytochrome P450, family 26, subfamily b, polypeptide 1) [NCBI Gene 232174] {aka CP26, P450RAI-2}, Chst9 (carbohydrate sulfotransferase 9) [NCBI Gene 71367] {aka 5430438D01Rik, GalNAc4ST-2, galNAc-4-ST2}, Frat2 (frequently rearranged in advanced T cell lymphomas 2) [NCBI Gene 212398]
- **Diseases:** LTD (MESH:D000088562), dislocation (MESH:D004204), aggression (MESH:D010554)
- **Chemicals:** iodixanol (MESH:C044834), OCT (MESH:C051883), chloride (MESH:D002712), glutamate (MESH:D018698), cyclic nucleotides (MESH:D009712), hexanes (MESH:D006586), CoAa-PAA (-), creatinine (MESH:D003404), DAPI (MESH:C007293), DA (MESH:D004298), PBS (MESH:D007854), farnesenes (MESH:D012717)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Mus musculus domesticus (western European house mouse, subspecies) [taxon 10092]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12919165/full.md

## References

76 references — full list in the complete paper: https://tomesphere.com/paper/PMC12919165/full.md

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Source: https://tomesphere.com/paper/PMC12919165