Translational profiling of mouse dopaminoceptive neurons reveals region-specific gene expression, exon usage, and striatal PGE2 modulatory effects - Institut du Fer à Moulin Access content directly
Journal Articles Molecular Psychiatry Year : 2022

Translational profiling of mouse dopaminoceptive neurons reveals region-specific gene expression, exon usage, and striatal PGE2 modulatory effects

Yuki Nakamura
Serge Luquet
Denis Hervé
  • Function : Author
  • PersonId : 924684
Emmanuel Valjent
Nicolas Gambardella
  • Function : Author
Jean‐antoine Girault

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.

Domains

Neurobiology
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Sup-Table-10_DEXSeq_D1_vs_D2__in-DS-and-NAc_analyses.xlsx (5.14 Mo) Télécharger le fichier
Sup-Table-11_DE-genes_DS-vs-NAc_revised.xlsx (730.38 Ko) Télécharger le fichier
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Sup-Table-13_DEXSeq_DS_vs_NAc_in-D1.xlsx (52.26 Mo) Télécharger le fichier
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Sup-Table-15_DEXSeq_DS_vs_NAc_in-D1-and-D2_analyses.xlsx (514.84 Ko) Télécharger le fichier
Sup-Table-16_DE-Transcription-factors_STR.xlsx (39.57 Ko) Télécharger le fichier
Sup-Table-17_IPA-upstream-analysis_DS-vs-NAc.xlsx (46.89 Ko) Télécharger le fichier
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Sup-Table-3_DE-genes_PFC-vs-STR.xlsx (1.48 Mo) Télécharger le fichier
Sup-Table-4_DEXSeq_PFC-vs-STR_in-D1.xlsx (54.8 Mo) Télécharger le fichier
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Sup-Table-8_DEXSeq_D1-vs-D2_in-DS.xlsx (53.71 Mo) Télécharger le fichier
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Dates and versions

hal-03583440 , version 1 (21-02-2022)

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Cite

Enrica Montalban, Albert Giralt, Lieng Taing, Evelien H S Schut, Laura F Supiot, et al.. Translational profiling of mouse dopaminoceptive neurons reveals region-specific gene expression, exon usage, and striatal PGE2 modulatory effects. Molecular Psychiatry, 2022, 27 (4), pp.2068-2079. ⟨10.1038/s41380-022-01439-4⟩. ⟨hal-03583440⟩
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