GEO series

Relapse to cocaine-seeking is regulated by medial habenula Nr4a2

GSE208081 Mus musculus (mouse) Single-nucleus RNA-seq 19 samples Submitted 2024/03/01 Platform GPL24247

At a glance

Single-nucleus RNA-seq · mouse · 19 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 19 samples: 19 samples, each with a distinct title — no replicated groupsGroups 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: Relapse to cocaine seeking is regulated by medial habenula NR4A2/NURR1 in miceCell reports · 2024

Summary (written by the submitters)

After exposure to drugs of abuse, the reward circuit can experience persistent changes that are thought to underlie relapse behavior. These changes can be epigenetic in nature, and here we identify an epigenetic regulator of memory processes, nuclear orphan receptor subfamily4 groupA member2 (NR4A2 aka NURR1), as necessary for relapse to cocaine-seeking behavior.

Read the full summary ↓

Nr4a2 is an epigenetically regulated immediate early gene and transcription factor that is highly expressed in the medial habenula (MHb). Despite the well-studied contributions of the MHb to nicotine-associated behaviors, the MHb is not classically included in reward circuits. Therefore, the role of MHb NR4A2 in cocaine-seeking and relapse behavior remains largely unknown. This is a key open question as NR4A2 is a powerful regulator of memory processes dependent on epigenetic mechanisms. In this study, we examined the role of MHb NR4A2 in cued reinstatement of cocaine self-administration in mice, and found that over-expressing a dominant negative form of Nr4a2 (Nurr2c) in the MHb results in a near complete block of relapse-like behavior. We used single-nucleus transcriptomics to characterize the molecular cascade following the manipulation of Nr4a2, revealing changes in transcriptional networks related to addiction, neuroplasticity, and glutamatergic signaling. Together, these results place the MHb in the reward circuit as a pivotal regulator of relapse behavior and demonstrate the importance of NR4A2 as a key mechanism driving relapse behavior in the MHb.

Published in

Relapse to cocaine seeking is regulated by medial habenula NR4A2/NURR1 in mice

Childs JE, Morabito S, Das S et al. · Cell reports 2024 · PMID 38489267 · doi:10.1016/j.celrep.2024.113956

This dataset

Open GSE208081 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 GSE208081_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA858117 and SRA study SRP386137. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38489267) ↗

Study design

19 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 19 sample titles: 19 distinct titles with little repetition. 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

GSM6336862 Sample-1, Nurr2c
GSM6336863 Sample-2, Nurr2c
GSM6336864 Sample-3, Nurr2c
GSM6336865 Sample-4, GFP
GSM6336866 Sample-5, GFP
GSM6336867 Sample-8, GFP
GSM6336868 Sample-9, GFP
GSM6336869 Sample-11, Nurr2c
GSM6336870 Sample-13, GFP
GSM6336871 Sample-14, Nurr2c
GSM6336872 Sample-16, Nurr2c
GSM8122631 Group3-4, NN
GSM8122632 Group3-6, NGFP
GSM8122633 Group3-5, NGFP
GSM8122634 Group3-3, NN
GSM8122635 Group3-8, NGFP
GSM8122636 Group3-1, NN
GSM8122637 Group3-7, NGFP
GSM8122638 Group3-2, NN

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GSE308643 A pathway from the anterior cingulate cortex to the lateral habenula controls chronic pain induced depression in male mice 22 samples shares habenula
GSE292434 Heterologous Prime-Boost Immunization of AAV-based Neoantigen Cancer Vaccine Induces Anti-Tumor Immunity to Inhibit Tumor Growth and Relapse 12 samples shares relapse
GSE241929 Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors 11 samples shares habenula

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