NPAS4 supports drug-cue associations and relapse-like behavior through regulation of the cell type-specific activation balance in the nucleus accumbens

Hughes, Brandon W.; Tsvetkov, Evgeny; Siemsen, Benjamin M.; Snyder, Kirsten K; Akiki, Rose Marie; Wood, D.J.; Penrod, Rachel D.; Scofield, Michael D.; Berto, Stefano; Taniguchi, Makoto; Cowan, Christopher W.

doi:10.1101/2022.09.04.506434

Cited by 3 publications

(2 citation statements)

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“…While these efforts have identified transcriptionally distinct subdivisions within larger D1-MSN and D2-MSN subclasses, the convergence of cell types and the reliability of specific marker genes across species remains unclear. Here, we leveraged published snRNA-seq datasets from the rat NAc to identify putative transcriptional markers of Grm8-MSNs, a poorly characterized population of neurons that has been identified in multiple rodent snRNA-seq datasets across different laboratories [33][34][35]44 . Notably, this cell population exhibits the highest expression of Oprm1 within the NAc, and is selectively marked by mRNA for the carbohydrate sulfotransferase gene Chst9.…”

Section: Discussionmentioning

confidence: 99%

Chst9Marks a Spatially and Transcriptionally Unique Population ofOprm1-Expressing Neurons in the Nucleus Accumbens

Andraka,

Phillips,

Brida

et al. 2023

Preprint

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Opioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (μORs). The μOR is encoded by theOprm1gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc).Oprm1expression in NAc medium spiny neurons (MSNs) mediates opioid place preference, seeking, and consumption. However, recent single nucleus RNA sequencing (snRNA-seq) studies in rodent, primate, and human NAc have revealed that multiple subpopulations of NAc neurons expressOprm1mRNA, making it unclear which populations mediate diverse behaviors resulting from μOR activation. Using published snRNA-seq datasets from the rat NAc, we identified a novel population of MSNs that express the highest levels ofOprm1of any NAc cell type. Here, we show that this population is selectively marked by expression ofChst9, a gene encoding a carbohydrate sulfotransferase. To validate this observation and characterize spatial localization of this population in the rat NAc, we performed multiplexed RNAscope fluorescence in situ hybridization studies to detect expression ofOprm1andChst9mRNA along with well-validated markers of MSNs. Notably,Chst9+ neurons exhibited more abundant expression ofOprm1as compared to other cell types, and formed discrete cellular clusters along the medial and ventral borders of the NAc shell subregion. Moreover,CHST9mRNA was also found to mark specific MSN populations in published human and primate snRNA-seq studies, indicating that this unique population may be conserved across species. Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression ofChst9. The abundant expression ofOprm1in this population and the conservation of these cells across species suggests that they may play a key functional role in opioid response and identify this subpopulation as a target for further investigation.

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Section: Discussionmentioning

confidence: 99%

Chst9Marks a Spatially and Transcriptionally Unique Population ofOprm1-Expressing Neurons in the Nucleus Accumbens

Andraka,

Phillips,

Brida

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…While these efforts have identified transcriptionally distinct subdivisions within larger D1-MSN and D2-MSN subclasses, the convergence of cell types and the reliability of specific marker genes across species remains unclear. Here, we leveraged published snRNA-seq datasets from the rat NAc to identify putative transcriptional markers of Grm8-MSNs, a poorly characterized population of neurons that has been identified in multiple rodent snRNA-seq datasets across different laboratories [ 33 – 35 , 44 ]. Notably, this cell population exhibits the highest expression of Oprm1 within the NAc, and is selectively marked by mRNA for the carbohydrate sulfotransferase gene Chst9 .…”

Section: Discussionmentioning

confidence: 99%