Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Translational profiling of mouse dopaminoceptive neurons reveals region-specific gene expression, exon usage, and striatal prostaglandin E2 modulatory effects

Abstract

Forebrain dopamine-sensitive (dopaminoceptive) neurons play a key role in movement, action selection, motivation, and working memory. Their activity is altered in Parkinson’s disease, addiction, schizophrenia, and other conditions, and drugs that stimulate or antagonize dopamine receptors have major therapeutic applications. Yet, similarities and differences between the various neuronal populations sensitive to dopamine have not been systematically explored. To characterize them, we compared translating mRNAs in the dorsal striatum and nucleus accumbens neurons expressing D1 or D2 dopamine receptor and prefrontal cortex neurons expressing D1 receptor. We identified genome-wide cortico-striatal, striatal D1/D2 and dorso/ventral differences in the translating mRNA and isoform landscapes, which characterize dopaminoceptive neuronal populations. Expression patterns and network analyses identified novel transcription factors with presumptive roles in these differences. Prostaglandin E2 (PGE2) was a candidate upstream regulator in the dorsal striatum. We pharmacologically explored this hypothesis and showed that misoprostol, a PGE2 receptor agonist, decreased the excitability of D2 striatal projection neurons in slices, and diminished their activity in vivo during novel environment exploration. We found that misoprostol also modulates mouse behavior including by facilitating reversal learning. Our study provides powerful resources for characterizing dopamine target neurons, new information about striatal gene expression patterns and regulation. It also reveals the unforeseen role of PGE2 in the striatum as a potential neuromodulator and an attractive therapeutic target.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: EGFP-L10a expression and differences in ribosome-associated mRNA expression in the PFC and striatum of D1-TRAP mice.
Fig. 2: Differential ribosome-associated mRNA expression in striatal regions of D1- and D2-TRAP mice.
Fig. 3: Expression of PGE2 receptors in the striatum and cell population-specific effects of PGE2 receptor stimulation.
Fig. 4: Effects of PGE2 receptor stimulation on electrophysiological properties of DS D1-SPNs and D2-SPNs.
Fig. 5: Effects of PGE2 receptor stimulation on DS neuron activity and mouse behavior.

Data availability

Sequencing data have been deposited in NCBI’s Gene Expression Omnibus and are accessible through GEO Series accession number GSE137153.

References

  1. Bjorklund A, Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci. 2007;30:194–202.

    PubMed  Google Scholar 

  2. Gerfen CR, Engber TM, Mahan LC, Susel Z, Chase TN, Monsma FJ Jr., et al. D1 and D2 dopamine receptor-regulated gene expression of striatonigral and striatopallidal neurons. Science. 1990;250:1429–32.

    CAS  PubMed  Google Scholar 

  3. Tecuapetla F, Jin X, Lima SQ, Costa RM. Complementary contributions of striatal projection pathways to action initiation and execution. Cell. 2016;166:703–15.

    CAS  PubMed  Google Scholar 

  4. Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev. 2011;63:182–217.

    CAS  PubMed  Google Scholar 

  5. Santana N, Mengod G, Artigas F. Quantitative analysis of the expression of dopamine D1 and D2 receptors in pyramidal and GABAergic neurons of the rat prefrontal cortex. Cereb Cortex. 2009;19:849–60.

    PubMed  Google Scholar 

  6. Khlghatyan J, Quintana C, Parent M, Beaulieu JM. High sensitivity mapping of cortical dopamine D2 receptor expressing neurons. Cereb Cortex. 2019;29:3813–27.

    PubMed  Google Scholar 

  7. Schultz W. Multiple dopamine functions at different time courses. Annu Rev Neurosci. 2007;30:259–88.

    CAS  PubMed  Google Scholar 

  8. Gerfen CR, Surmeier DJ. Modulation of striatal projection systems by dopamine. Annu Rev Neurosci. 2011;34:441–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Girault JA. Signaling in striatal neurons: the phosphoproteins of reward, addiction, and dyskinesia. Prog Mol Biol Transl Sci. 2012;106:33–62.

    CAS  PubMed  Google Scholar 

  10. Simpson EH, Gallo EF, Balsam PD, Javitch JA, Kellendonk C. How changes in dopamine D2 receptor levels alter striatal circuit function and motivation. Mol Psychiatry. 2021.

  11. Mitchell IJ, Cooper AJ, Griffiths MR. The selective vulnerability of striatopallidal neurons. Prog Neurobiol. 1999;59:691–719.

    CAS  PubMed  Google Scholar 

  12. Volkow ND, Fowler JS, Wang GJ, Swanson JM. Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Mol Psychiatry. 2004;9:557–69.

    CAS  PubMed  Google Scholar 

  13. Heiman M, Heilbut A, Francardo V, Kulicke R, Fenster RJ, Kolaczyk ED, et al. Molecular adaptations of striatal spiny projection neurons during levodopa-induced dyskinesia. Proc Natl Acad Sci USA. 2014;111:4578–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Heiman M, Schaefer A, Gong S, Peterson JD, Day M, Ramsey KE, et al. A translational profiling approach for the molecular characterization of CNS cell types. Cell. 2008;135:738–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Lobo MK, Karsten SL, Gray M, Geschwind DH, Yang XW. FACS-array profiling of striatal projection neuron subtypes in juvenile and adult mouse brains. Nat Neurosci. 2006;9:443–52.

    CAS  PubMed  Google Scholar 

  16. Ena SL, De Backer JF, Schiffmann SN, de Kerchove d’Exaerde A. FACS array profiling identifies Ecto-5’ nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning. J Neurosci. 2013;33:8794–809.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Belin D, Jonkman S, Dickinson A, Robbins TW, Everitt BJ. Parallel and interactive learning processes within the basal ganglia: relevance for the understanding of addiction. Behav Brain Res. 2009;199:89–102.

    PubMed  Google Scholar 

  18. Gokce O, Stanley GM, Treutlein B, Neff NF, Camp JG, Malenka RC, et al. Cellular taxonomy of the mouse striatum as revealed by single-cell RNA-seq. Cell Rep. 2016;16:1126–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Ho H, Both M, Siniard A, Sharma S, Notwell JH, Wallace M, et al. A guide to single-cell transcriptomics in adult rodent brain: the medium spiny neuron transcriptome revisited. Front Cell Neurosci. 2018;12:159.

    PubMed  PubMed Central  Google Scholar 

  20. Munoz-Manchado AB, Bengtsson Gonzales C, Zeisel A, Munguba H, Bekkouche B, Skene NG, et al. Diversity of interneurons in the dorsal striatum revealed by single-cell RNA sequencing and PatchSeq. Cell Rep. 2018;24:2179–90.e7.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Doyle JP, Dougherty JD, Heiman M, Schmidt EF, Stevens TR, Ma G, et al. Application of a translational profiling approach for the comparative analysis of CNS cell types. Cell. 2008;135:749–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Heiman M, Kulicke R, Fenster RJ, Greengard P, Heintz N. Cell type-specific mRNA purification by translating ribosome affinity purification (TRAP). Nat Protoc. 2014;9:1282–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Andrews S. FastQC: a quality control tool for high throughput sequence data. https://www.bioinformaticsbabrahamacuk/projects/fastqc/. 2010.

  24. Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements. Nat Methods. 2015;12:357–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Andrews S. SeqMonk: a tool to visualise and analyse high throughput mapped sequence data. https://www.bioinformaticsbabrahamacuk/projects/seqmonk/. 2008.

  26. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15:550.

    PubMed  PubMed Central  Google Scholar 

  27. Wang L, Wang S, Li W. RSeQC: quality control of RNA-seq experiments. Bioinformatics. 2012;28:2184–5.

    CAS  PubMed  Google Scholar 

  28. Anders S, Reyes A, Huber W. Detecting differential usage of exons from RNA-seq data. Genome Res. 2012;22:2008–17.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Consortium TD, Marbach D, Costello JC, Küffner R, Vega NM, Prill RJ, et al. Wisdom of crowds for robust gene network inference. Nat Methods. 2012;9:796–804.

    Google Scholar 

  30. Faith JJ, Hayete B, Thaden JT, Mogno I, Wierzbowski J, Cottarel G, et al. Large-scale mapping and validation of Escherichia coli transcriptional regulation from a compendium of expression profiles. PLoS Biol. 2007;5:e8.

    PubMed  PubMed Central  Google Scholar 

  31. Huynh-Thu VA, Irrthum A, Wehenkel L PG. Inferring regulatory networks from expression data using tree-based methods. PLoS ONE. 2010;5:e12776.

    PubMed  PubMed Central  Google Scholar 

  32. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Rmage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13:2498–504.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Puighermanal E, Castell L, Esteve-Codina A, Melser S, Kaganovsky K, Zussy C, et al. Functional and molecular heterogeneity of D2R neurons along dorsal ventral axis in the striatum. Nat Commun. 2020;11:1957.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Denisenko-Nehrbass N, Oguievetskaia K, Goutebroze L, Galvez T, Yamakawa H, Ohara O, et al. Protein 4.1B associates with both Caspr/paranodin and Caspr2 at paranodes and juxtaparanodes of myelinated fibres. Eur J Neurosci. 2003;17:411–6.

    PubMed  Google Scholar 

  35. Alcacer C, Santini E, Valjent E, Gaven F, Girault JA, Herve D. Galpha(olf) mutation allows parsing the role of cAMP-dependent and extracellular signal-regulated kinase-dependent signaling in L-3,4-dihydroxyphenylalanine-induced dyskinesia. J Neurosci. 2012;32:5900–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Biever A, Puighermanal E, Nishi A, David A, Panciatici C, Longueville S, et al. PKA-dependent phosphorylation of ribosomal protein S6 does not correlate with translation efficiency in striatonigral and striatopallidal medium-sized spiny neurons. J Neurosci. 2015;35:4113–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Anglada-Huguet M, Vidal-Sancho L, Giralt A, Garcia-Diaz Barriga G, Xifro X, Alberch J. Prostaglandin E2 EP2 activation reduces memory decline in R6/1 mouse model of Huntington’s disease by the induction of BDNF-dependent synaptic plasticity. Neurobiol Dis. 2016;95:22–34.

    CAS  PubMed  Google Scholar 

  38. Meye FJ, Valentinova K, Lecca S, Marion-Poll L, Maroteaux MJ, Musardo S, et al. Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula. Nat Neurosci. 2015;18:376–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Berland C, Montalban E, Perrin E, Di Miceli M, Nakamura Y, Martinat M, et al. Circulating triglycerides gate dopamine-associated behaviors through DRD2-expressing neurons. Cell Metab. 2020;31:773–90.e11.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Lerner TN, Shilyansky C, Davidson TJ, Evans KE, Beier KT, Zalocusky KA, et al. Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits. Cell. 2015;162:635–47.

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Oliveira MG, Bueno OF, Pomarico AC, Gugliano EB. Strategies used by hippocampal- and caudate-putamen-lesioned rats in a learning task. Neurobiol Learn Mem. 1997;68:32–41.

    CAS  PubMed  Google Scholar 

  42. Bertran-Gonzalez J, Bosch C, Maroteaux M, Matamales M, Herve D, Valjent E, et al. Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. J Neurosci. 2008;28:5671–85.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Rakhilin SV, Olson PA, Nishi A, Starkova NN, Fienberg AA, Nairn AC, et al. A network of control mediated by regulator of calcium/calmodulin-dependent signaling. Science. 2004;306:698–701.

    CAS  PubMed  Google Scholar 

  44. Ouimet CC, Hemmings HC Jr., Greengard P. ARPP-21, a cyclic AMP-regulated phosphoprotein enriched in dopamine-innervated brain regions. II. Immunocytochemical localization in rat brain. J Neurosci. 1989;9:865–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Kisielow J, Nairn AC, Karjalainen K. TARPP, a novel protein that accompanies TCR gene rearrangement and thymocyte education. Eur J Immunol. 2001;31:1141–9.

    CAS  PubMed  Google Scholar 

  46. Rehfeld F, Maticzka D, Grosser S, Knauff P, Eravci M, Vida I, et al. The RNA-binding protein ARPP21 controls dendritic branching by functionally opposing the miRNA it hosts. Nat Commun. 2018;9:1235.

    PubMed  PubMed Central  Google Scholar 

  47. Dawson VL, Dawson TM, Filloux FM, Wamsley JK. Evidence for dopamine D-2 receptors on cholinergic interneurons in the rat caudate-putamen. Life Sci. 1988;42:1933–9.

    CAS  PubMed  Google Scholar 

  48. Gangarossa G, Espallergues J, de Kerchove d’Exaerde A, El Mestikawy S, Gerfen CR, Herve D, et al. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse nucleus accumbens. Front Neural Circuits. 2013;7:22.

    PubMed  PubMed Central  Google Scholar 

  49. Kupchik YM, Brown RM, Heinsbroek JA, Lobo MK, Schwartz DJ, Kalivas PW. Coding the direct/indirect pathways by D1 and D2 receptors is not valid for accumbens projections. Nat Neurosci. 2015;18:1230–2.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Treutlein B, Gokce O, Quake SR, Sudhof TC. Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing. Proc Natl Acad Sci USA. 2014;111:E1291–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Voorn P, Vanderschuren LJ, Groenewegen HJ, Robbins TW, Pennartz CM. Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci. 2004;27:468–74.

    CAS  PubMed  Google Scholar 

  52. Saint-Martin M, Joubert B, Pellier-Monnin V, Pascual O, Noraz N, Honnorat J. Contactin-associated protein-like 2, a protein of the neurexin family involved in several human diseases. Eur J Neurosci. 2018;48:1906–23.

    PubMed  Google Scholar 

  53. Chen N, Koopmans F, Gordon A, Paliukhovich I, Klaassen RV, van der Schors RC, et al. Interaction proteomics of canonical Caspr2 (CNTNAP2) reveals the presence of two Caspr2 isoforms with overlapping interactomes. Biochim Biophys Acta. 2015;1854:827–33.

    CAS  PubMed  Google Scholar 

  54. Garel S, Marin F, Grosschedl R, Charnay P. Ebf1 controls early cell differentiation in the embryonic striatum. Development. 1999;126:5285–94.

    CAS  PubMed  Google Scholar 

  55. Lobo MK, Yeh C, Yang XW. Pivotal role of early B-cell factor 1 in development of striatonigral medium spiny neurons in the matrix compartment. J Neurosci Res. 2008;86:2134–46.

    CAS  PubMed  Google Scholar 

  56. Lu KM, Evans SM, Hirano S, Liu FC. Dual role for Islet-1 in promoting striatonigral and repressing striatopallidal genetic programs to specify striatonigral cell identity. Proc Natl Acad Sci USA. 2014;111:E168–77.

    CAS  PubMed  Google Scholar 

  57. Zhang Q, Zhang Y, Wang C, Xu Z, Liang Q, An L, et al. The zinc finger transcription factor Sp9 is required for the development of striatopallidal projection neurons. Cell Rep. 2016;16:1431–44.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Martin-Ibanez R, Pardo M, Giralt A, Miguez A, Guardia I, Marion-Poll L, et al. Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons. Development. 2017;144:1566–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Anderson SA, Qiu M, Bulfone A, Eisenstat DD, Meneses J, Pedersen R, et al. Mutations of the homeobox genes Dlx-1 and Dlx-2 disrupt the striatal subventricular zone and differentiation of late born striatal neurons. Neuron. 1997;19:27–37.

    CAS  PubMed  Google Scholar 

  60. Wapinski OL, Vierbuchen T, Qu K, Lee QY, Chanda S, Fuentes DR, et al. Hierarchical mechanisms for direct reprogramming of fibroblasts to neurons. Cell. 2013;155:621–35.

    CAS  PubMed  Google Scholar 

  61. Hoekman MF, Jacobs FM, Smidt MP, Burbach JP. Spatial and temporal expression of FoxO transcription factors in the developing and adult murine brain. Gene Expr Patterns. 2006;6:134–40.

    CAS  PubMed  Google Scholar 

  62. Sellnow RC, Steece-Collier K, Altwal F, Sandoval IM, Kordower JH, Collier TJ, et al. Striatal Nurr1 facilitates the dyskinetic state and exacerbates levodopa-induced dyskinesia in a rat model of Parkinson’s disease. J Neurosci. 2020;40:3675–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Steece-Collier K, Collier TJ, Lipton JW, Stancati JA, Winn ME, Cole-Strauss A, et al. Striatal Nurr1, but not FosB expression links a levodopa-induced dyskinesia phenotype to genotype in Fisher 344 vs. Lewis hemiparkinsonian rats. Exp Neurol. 2020;330:113327.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. van der Raadt J, van Gestel SHC, Nadif Kasri N, Albers CA. ONECUT transcription factors induce neuronal characteristics and remodel chromatin accessibility. Nucleic Acids Res. 2019;47:5587–602.

    PubMed  PubMed Central  Google Scholar 

  65. de Munnik SA, Garcia-Minaur S, Hoischen A, van Bon BW, Boycott KM, Schoots J, et al. A de novo non-sense mutation in ZBTB18 in a patient with features of the 1q43q44 microdeletion syndrome. Eur J Hum Genet. 2014;22:844–6.

    PubMed  Google Scholar 

  66. Kitaoka S, Furuyashiki T, Nishi A, Shuto T, Koyasu S, Matsuoka T, et al. Prostaglandin E2 acts on EP1 receptor and amplifies both dopamine D1 and D2 receptor signaling in the striatum. J Neurosci. 2007;27:12900–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. Prostanoid receptors: subtypes and signaling. Annu Rev Pharm Toxicol. 2001;41:661–90.

    CAS  Google Scholar 

  68. Cui G, Jun SB, Jin X, Pham MD, Vogel SS, Lovinger DM, et al. Concurrent activation of striatal direct and indirect pathways during action initiation. Nature. 2013;494:238–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Hooper KC, Banks DA, Stordahl LJ, White IM, Rebec GV. Quinpirole inhibits striatal and excites pallidal neurons in freely moving rats. Neurosci Lett. 1997;237:69–72.

    CAS  PubMed  Google Scholar 

  70. Baudonnat M, Huber A, David V, Walton ME. Heads for learning, tails for memory: reward, reinforcement and a role of dopamine in determining behavioral relevance across multiple timescales. Front Neurosci. 2013;7:175.

    PubMed  PubMed Central  Google Scholar 

  71. Watson DJ, Stanton ME. Spatial discrimination reversal learning in weanling rats is impaired by striatal administration of an NMDA-receptor antagonist. Learn Mem. 2009;16:564–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Sala-Bayo J, Fiddian L, Nilsson SRO, Hervig ME, McKenzie C, Mareschi A, et al. Dorsal and ventral striatal dopamine D1 and D2 receptors differentially modulate distinct phases of serial visual reversal learning. Neuropsychopharmacol. 2020;45:736–44.

    CAS  Google Scholar 

  73. Victor MB, Richner M, Hermanstyne TO, Ransdell JL, Sobieski C, Deng PY, et al. Generation of human striatal neurons by microRNA-dependent direct conversion of fibroblasts. Neuron. 2014;84:311–23.

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Ehrlich AT, Furuyashiki T, Kitaoka S, Kakizuka A, Narumiya S. Prostaglandin E receptor EP1 forms a complex with dopamine D1 receptor and directs D1-induced cAMP production to adenylyl cyclase 7 through mobilizing G(betagamma) subunits in human embryonic kidney 293T cells. Mol Pharmacol. 2013;84:476–86.

    CAS  PubMed  Google Scholar 

  75. Johnson PM, Kenny PJ. Dopamine D2 receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nat Neurosci. 2010;13:635–41.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The paper is dedicated to the memory of PG who passed away on April 13th, 2019, before the paper was completed. Authors thank the Babraham Institute’s Bioinformatics team for help with read mapping and counting, Vincent Knight-Shrijver for his volcano-plot R script, and Lucile Marion-Poll for helpful suggestions.

Funding

This work was supported by Inserm and Sorbonne Université, and grants from European Research Council (ERC, AdG-250349) and Biology for Psychiatry Laboratory of excellence (Labex Bio-Psy, Investissements d’Avenir, ANR-11-IDEX-0004-02) to JAG, Fondation pour la Recherche Médicale (FRM # DPA20140629798) and ANR (Epitraces, ANR-16-CE16-0018) to JAG and EV, ANR-17-CE37-0007 (Metacognition) to CM, the United States Army Medical Research and Material Command (USAMRMC) Award No. W81XWH-14-1-0046 to JPR, the Fisher Center for Alzheimer’s Disease Research to JPR and PG, NIH grants DA018343 and DA040454 to ACN. EM was supported by a Marie Curie International Training Network (ITN) N-PLAST. AG is a Ramón y Cajal fellow (RYC-2016-19466) and is supported by a grant from the Spain Ministerio de Ciencia, Innovación y Universidades (Project no. RTI2018-094678-A-I00). LC was supported by a Labex EpiGenMed PhD fellowship (Investissements d’avenir, ANR-10-LABX-12-01). YN was recipient of Uehara Memorial Foundation and Fyssen Foundation fellowships. BdP was supported by FRM (FDT201805005390). NG was supported by BBSRC (BB/P013406/1, BB/P013414/1, BB/P013384/1). KDN received an Amgen Scholarship. LV received support from the Erasmus + program. Work in FJM lab was supported by the ERC under the European Union’s Horizon 2020 research and innovation program (grant agreement 804089; ReCoDE) and the NWO Gravitation project BRAINSCAPES: A Roadmap from Neurogenetics to Neurobiology (024.004.012).

Author information

Authors and Affiliations

Authors

Contributions

JAG and JPR conceived and supervised the project. AG, CM, DH, EM, EV, FJM, JAG, JPR, LG, and NG designed the experiments. AG, AP, BdP, CM, EHSS, EM, EV, JPR, LC, LG, JC, LFS, PT, FJM, and YN performed experiments. ACN, AG, CM, DH, EM, EV, FJM, LG, JAG, and JPR analyzed data, JPR, KDN, LT, LV, NG, and WW performed and interpreted bioinformatics analyses, ACN, AG, AP, BdP, CM, DH, EM, EV, FJM, JAG, LG, LT, NG, NH, PG, SL, and YN discussed the data and provided input and corrections to the paper. EM, JPR, and JAG wrote the paper. All the authors but PG approved the final version of the paper.

Corresponding authors

Correspondence to Jean-Pierre Roussarie or Jean-Antoine Girault.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Methods

Supplementary Figures

List of Supplementary Tables

R script used for network inference

Supplementary Tables 1

Supplementary Table 2

Supplementary Table 3: DE-genes_PFC-vs-striatum

Supplementary Table 4: DEXSeq_PFC-vs-Str_in-D1

Supplementary Table 5: DEXSeq_PFC-vs-Str_in-D1_Analyses

Supplementary Table 6: DE-genes_D1-vs-D2_in-Str

Supplementary Table 7: DE-genes_D1-vs-D2_in-STR_GO-IUPHAR

Supplementary Table 8: DEXSeq_D1-vs-D2_in-DS

Supplementary Table 9: DEXSeq_D1-vs-D2_in-NAc

Supplementary Table 10: DEXSeq_D1-vs-D2_in-DS-and-NAc_Analyses

Supplementary Table 11: DE-genes_DS-vs-NAc

Supplementary Table 12: DE-genes_DS-vs-NAc_GO-IUPHAR

Supplementary Table 13: DEXSeq_DS-vs-NAc_in-D1

Supplementary Table 14: DEXSeq_DS-vs-NAc_in-D2

Supplementary Table 15: DEXSeq_DS-vs-NAc_in-D1-and-D2_Analyses

Supplementary Table 16: DE-Transcription-factors_STR

Supplementary Table 17: IPA-upstream-analysis_DS-vs-NAc

Supplementary Table 18: Prostaglandin-related-gene products

Supplementary Table 19: Statistical analyses

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Montalban, E., Giralt, A., Taing, L. et al. Translational profiling of mouse dopaminoceptive neurons reveals region-specific gene expression, exon usage, and striatal prostaglandin E2 modulatory effects. Mol Psychiatry 27, 2068–2079 (2022). https://doi.org/10.1038/s41380-022-01439-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-022-01439-4

Search

Quick links