 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 09, 2023 |
| Title |
A single-cell atlas of gene expression and chromatin accessibility changes associated with cocaine addiction in the rat amygdala (snATAC-Seq Multiome) |
| Organism |
Rattus norvegicus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The amygdala plays a key role in the negative emotional states associated with the relapse to drug seeking behavior. Neuroanatomical and functional observations have uncovered the role of discrete amygdala subregions in different aspects of these negative affective states. However, the underlying transcriptional regulatory programs driving the function of distinct amygdala cell types remains unknown. We generated an atlas of single nucleus gene expression and chromatin accessibility in the amygdala of rats with low and high cocaine addiction-like behaviors after prolonged abstinence from extended access to cocaine intravenous self-administration. We identified thousands of cell type-specific differentially expressed genes, suggesting that negative affective states are associated with cell type-specific mechanisms which are enriched for molecular pathways, including energy metabolism and GABAergic synapses in excitatory and somatostatin neurons. We demonstrate that higher addiction severity is linked to excessive GABAergic inhibition and, using pharmacological inhibition, we find that addiction-like phenotypes are regulated by the metabolite methylglyoxal which is an agonist at GABA-A receptors. By analyzing differences in chromatin accessibility, we predict upstream transcriptional regulators associated with addiction-like behavior and find discordant regulation of key transcription factors among distinct cell populations. Overall, we provide a comprehensive characterization of cell type-specific transcriptional changes in the amygdala during protracted abstinence and use these insights to identify a novel target for pharmacological intervention.
|
| |
|
| Overall design |
snRNA-seq and snATAC-seq data generated using 10X Genomics Chromium Single Cell Multiome ATAC + Gene Expression
|
| |
|
| Contributor(s) |
Zhou JL, Guglielmo GD, Ho AJ, Kallupi M, Pokhrel N, Li H, Chitre AS, Munro D, Mohammadi P, Carrette LL, George O, Palmer AA, McVicker GP, Telese F |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jun 20, 2023 |
| Last update date |
Aug 10, 2023 |
| Contact name |
Jessica Lu Zhou |
| Organization name |
University of California San Diego
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
California |
| ZIP/Postal code |
92093-0603 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL20084 |
Illumina NextSeq 500 (Rattus norvegicus) |
|
| Samples (2) |
|
| This SubSeries is part of SuperSeries: |
| GSE212417 |
Cocaine addiction-like behaviors are associated with long-term changes in gene regulation, energy metabolism, and GABAergic inhibition within the amygdala |
|
| Relations |
| BioProject |
PRJNA985691 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE235317_RAW.tar |
3.2 Gb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
|
|
|
|
 |
