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Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacy

GSE309750 Mus musculus (mouse) RNA-seq (gene expression) 34 samples Submitted 2026/05/27 Platform GPL17021
At a glance

RNA-seq (gene expression) · mouse · 34 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
34 samples: 6 conditions, mostly with about 7 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacyMolecular psychiatry · 2026
Summary (written by the submitters)
elective serotonin reuptake inhibitors (SSRIs) exhibit delayed therapeutic effects despite rapid serotonin elevation, suggesting their dependence on slow neuroplastic adaptations. Here, we demonstrate that antidepressant actions require cell type-specific translational regulation of the peptidergic signaling in the dentate gyrus (DG).
Read the full summary ↓
Chronic, but not acute, treatment with an SSRI fluoxetine selectively enhances translational activity in hilar mossy cells (MCs), with no detectable changes in neighboring granule cells (GCs). Combining Translating Ribosome Affinity Purification (TRAP) with RNA sequencing revealed distinct baseline translatomes between these two glutamatergic neurons and identified fluoxetine-induced remodeling of peptidergic pathways in the DG. Crucially, we discovered MC-specific enrichment of the neuropeptide PACAP, which undergoes translation-dependent upregulation by chronic fluoxetine treatment. This PACAP induction mediates neuroadaptive plasticity in PAC1 receptor-expressing GCs and drives behavioral responses prominently in female mice during prolonged SSRI administration. Our findings establish cell type-specific translational reprogramming as a novel mechanistic framework for antidepressant action.
Published in
Translational reprogramming of dentate gyrus peptidergic circuitry gates antidepressant efficacy
Oh SJ, Jang JH, Roussarie JP et al. · Molecular psychiatry 2026 · PMID 41634134 · doi:10.1038/s41380-026-03461-2
This dataset
Open GSE309750 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE309750_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1336863 and SRA study SRP630180. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41634134) ↗
Study design
6 conditions, mostly with about 7 replicates each
HC_FLX ×7 MC_FLX ×7 HC_VEH ×6 MC_VEH ×6 GC_VEH ×4 GC_FLX ×4

Supports a between-group comparison across 34 samples.

How we read this: 6 replicated groups read from 34 sample titles; they account for 34 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
Datasets on a similar topic

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