GeneSet Information

Tier IV GS408379 • Differential gene expression in nucleus accumbens somatostatin interneurons that regulate behavioral responses to cocaine in mice_pvalue

DESCRIPTION:

To characterize transcriptional alterations that cocaine induces in these cells, we perform cell type-specific RNA-sequencing on FACS-isolated nuclei of somatostatin interneurons and identified 1100 DETs enriched for processes related to neural plasticity. To profile the entire (non poly-A selected) transcriptome of NAc somatostatin interneurons, we generated a transgenic reporter line (SST-TLG498 mice) to label the nuclei of these cells with a modified form of EGFP that is retained in the nuclear membrane (EGFP-F)22, enabling their isolation from NAc dissections using FACS. We succeeded in FACS-isolating nuclei suitable for RNA-sequencing from individual SST-TLG498 mice. We proceeded with differential expression analysis of the RNA-sequencing data to identify differentially expressed transcripts (DETs) in NAc somatostatin interneurons in response to repeated cocaine exposure: 778 transcripts were upregulated by cocaine and 322 were downregulated.

LABEL:

Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_pvalue

SCORE TYPE:

P-Value

DATE ADDED:

2024-03-28

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Efrain A Ribeiro, Marine Salery, Joseph R Scarpa, Erin S Calipari, Peter J Hamilton, Stacy M Ku, Hope Kronman, Immanuel Purushothaman, Barbara Juarez, Mitra Heshmati, Marie Doyle, Casey Lardner, Dominicka Burek, Ana Strat, Stephen Pirpinias, Ezekiell Mouzon, Ming-Hu Han, Rachael L Neve, Rosemary C Bagot, Andrew Kasarskis, Ja Wook Koo, Eric J Nestler

TITLE:

Transcriptional and physiological adaptations in nucleus accumbens somatostatin interneurons that regulate behavioral responses to cocaine.

JOURNAL:

Nature communications 08 2018, Vol 9, pp. 3149

ABSTRACT:

The role of somatostatin interneurons in nucleus accumbens (NAc), a key brain reward region, remains poorly understood due to the fact that these cells account for < 1% of NAc neurons. Here, we use optogenetics, electrophysiology, and RNA-sequencing to characterize the transcriptome and functioning of NAc somatostatin interneurons after repeated exposure to cocaine. We find that the activity of somatostatin interneurons regulates behavioral responses to cocaine, with repeated cocaine reducing the excitability of these neurons. Repeated cocaine also induces transcriptome-wide changes in gene expression within NAc somatostatin interneurons. We identify the JUND transcription factor as a key regulator of cocaine action and confirmed, by use of viral-mediated gene transfer, that JUND activity in somatostatin interneurons influences behavioral responses to cocaine. Our results identify alterations in NAc induced by cocaine in a sparse population of somatostatin interneurons, and illustrate the value of studying brain diseases using cell type-specific whole transcriptome RNA-sequencing. PUBMED: 30089879
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Annotation Information

No sequence read archive data associated with this GeneSet.


Brain (D001921)
Disease (D004194)
Population (D011153)
Forms (D020478)
RNA (D012313)
Mice (D051379)
Dissection (D004210)
Gene Expression (D015870)
Role (D012380)
Neurons (D009474)
Interneurons (D007395)
Nucleus Accumbens (D009714)
Somatostatin (D013004)
Cocaine (D003042)
Cells (D002477)
Brain Diseases (D001927)
Reward (D012201)
Electrophysiology (D004594)
accumbens nucleus (MA:0000892)
brain (MA:0000168)
transcription, DNA-dependent (GO:0006351)
membrane (GO:0016020)
nascent polypeptide-associated complex (GO:0005854)
nucleus (GO:0005634)
nuclear membrane (GO:0031965)
gene expression (GO:0010467)
RNA (EDAM_topic:0099)
Analysis (EDAM_operation:2945)
Cell biology resources (EDAM_topic:2229)
Sequencing (EDAM_topic:3168)
Transcriptomics (EDAM_topic:0203)
Transcription (EDAM_topic:0110)
Data (EDAM_data:0006)
Gene expression data processing (EDAM_operation:2495)
Differential expression analysis (EDAM_operation:3223)
rna (EDAM_format:1213)
Type (EDAM_data:2100)
N-acetyl-L-cysteine (CHEBI:28939)
Fluthiacet methyl (CHEBI:5133)
label (CHEBI:35209)
cocaine (CHEBI:27958)
cocaine(1+) (CHEBI:60056)
NAC (CHEBI:7421)
somatostatin (CHEBI:64628)
ribonucleic acid (CHEBI:33697)
role (CHEBI:50906)
atomic nucleus (CHEBI:33252)
disease (EFO:0000408)
individual (EFO:0000542)
cell type (EFO:0000324)
dissection (EFO:0003856)
obsolete_accumbens nucleus (EFO:0000906)
fluorescence-activated cell sorting method (MMO:0000310)
transgenic in situ reporter assay (MMO:0000671)
rostral octaval nerve motor nucleus (UBERON:2002175)
brain (UBERON:0000955)
membrane organ (UBERON:0000094)
neural nucleus (UBERON:0000125)
nucleus accumbens (UBERON:0001882)
sagittal stratum (UBERON:0035931)
anatomical projection (UBERON:0004529)
membranous layer (UBERON:0000158)
adult cerebral ganglion (UBERON:6110636)
DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981)

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Supported by NIH R01 AA18776 jointly funded by NIAAA and NIDA, and JAX Center for Precision Genetics NIH U54 OD 020351