Transcriptome profiling of the ventral pallidum reveals a role for pallido-thalamic neurons in cocaine reward
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA821246 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18529508_1.fastq.gz | Fastqsanger.gz | |||
| SRR18529508_2.fastq.gz | Fastqsanger.gz | |||
| SRR18529509_1.fastq.gz | Fastqsanger.gz | |||
| SRR18529509_2.fastq.gz | Fastqsanger.gz | |||
| SRR18529510_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Using RNAseq, we evaluated transcriptomic changes in the ventral pallidum (VP) of mice 24h following 10 days of cocaine self-administration.
2022-06-13 | GSE199725 | GEO
Project description:Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in VTA. By reducing H3Q5dop in VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated cue-induced dopamine release in nucleus accumbens and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in VTA.
2020-05-19 | GSE124055 | GEO
Project description:Psychostimulant exposure alters the activity of ventral pallidum (VP) projection neurons. However, the molecular underpinnings of these circuit dysfunctions are unclear. We used RNA-sequencing to reveal alterations in the transcriptional landscape of the VP that are induced by cocaine self-administration in mice. We then probed gene expression in select VP neuronal subpopulations to isolate a circuit associated with cocaine intake. Finally, we used both overexpression and CRISPR-mediated knockdown to test the role of a gene target on cocaine-mediated behaviors as well as dendritic spine density. Our results showed that a large proportion (55%) of genes associated with structural plasticity were changed 24 h following cocaine intake. Among them, the transcription factor Nr4a1 (Nuclear receptor subfamily 4, group A, member 1, or Nur77) showed high expression levels. We found that the VP to mediodorsal thalamus (VP → MDT) projection neurons specifically were recapitulating this increase in Nr4a1 expression. Overexpressing Nr4a1 in VP → MDT neurons enhanced drug-seeking and drug-induced reinstatement, while Nr4a1 knockdown prevented self-administration acquisition and subsequent cocaine-mediated behaviors. Moreover, we showed that Nr4a1 negatively regulated spine dynamics in this specific cell subpopulation. Together, our study identifies for the first time the transcriptional mechanisms occurring in VP in drug exposure. Our study provides further understanding on the role of Nr4a1 in cocaine-related behaviors and identifies the crucial role of the VP → MDT circuit in drug intake and relapse-like behaviors.
| S-EPMC9722585 | biostudies-literature
Project description:All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance use disorders. Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behavior1. Here, we explored the role of myelin plasticity in dopaminergic circuity and reward learning. We demonstrate that dopaminergic neuronal activity-regulated myelin plasticity is a key modulator of dopaminergic circuit function and opioid reward. Oligodendroglial lineage cells respond to dopaminergic neuronal activity evoked by either optogenetic stimulation of dopaminergic neurons, optogenetic inhibition of GABAergic neurons, or administration of morphine or cocaine. These oligodendroglial changes are evident selectively within the ventral tegmental area (VTA), but not along the axonal projections in the medial forebrain bundle nor within the target nucleus accumbens (NAc). Genetic blockade of oligodendrogenesis dampens dopamine release dynamics in nucleus accumbens and impairs behavioral conditioning to morphine. Taken together, these findings underscore a critical role for oligodendrogenesis in reward learning and identify dopaminergic neuronal activity-regulated myelin plasticity as an important circuit modification that is required for opioid reward.
2024-02-10 | GSE255072 | GEO
Project description:Dopamine (DA) signaling plays an essential role in reward valence attribution and in encoding the reinforcing properties of natural and artificial rewards. The adaptive responses from midbrain dopamine neurons to artificial rewards such as drugs of abuse are therefore important for understanding the development of substance use disorders. Drug-induced changes in gene expression are one such adaptation that can determine the activity of dopamine signaling in projection regions of the brain reward system. One of the major challenges to obtaining this understanding is the inherent cellular heterogeneity in the brain, where each neuron population can be defined by a distinct transcriptional profile. To bridge this gap, we have adapted a virus-based method for labeling and capture of dopamine nuclei, coupled with nuclear RNA-sequencing and bioinformatics analyses, to study the transcriptional adaptations, specifically, of dopamine neurons in the ventral tegmental area (VTA) during cocaine taking and cocaine craving, using a mouse model of cocaine intravenous self-administration (IVSA). Our results show significant changes in gene expression across non-drug operant training, cocaine taking, and cocaine craving, highlighted by an enrichment in expression of repressive epigenetic modifying enzymes during cocaine craving. Immunohistochemical validation further revealed an increase of H3K9me3 deposition in DA neurons during cocaine craving. These results demonstrate that cocaine-induced transcriptional adaptations in dopamine neurons vary by phase of self-administration and suggest that such an approach may be useful in identifying relevant phase-specific molecular targets to alter the behavioral course of substance use disorders.
2024-11-22 | GSE277757 | GEO
Project description:Global changes in gene expression that underlie the circuit and behavioral dysregulation associated with cocaine addiction remain incompletely understood. Here, we determined how a history of cocaine self-administration (SA) “re-programs” transcriptome-wide responses at baseline and in response to cocaine re-exposure after prolonged withdrawal (WD). We assigned male mice to one of six groups: saline or cocaine SA + 24 hr WD; or saline/cocaine SA + 30 d WD + an acute saline/cocaine challenge within the previous drug-paired context. RNA-seq was then conducted on six interconnected brain reward regions. We focused on patterns of gene expression that were altered by cocaine SA, in particular, molecular targets that show priming or desensitization upon re-exposure to cocaine. Genes that were affected uniquely by acute cocaine after cocaine SA+WD displayed region-specific regulation. The greatest number of regulated genes were seen in nucleus accumbens, dorsal striatum, and basolateral amygdala. Further analysis revealed several transcription factors as key upstream regulators in these three regions, including several not previously implicated in cocaine action. Regulation of subsets of these primed and desensitized genes correlated robustly with SA behavior displayed by individual mice. For example, analysis of transcriptome-wide expression changes revealed that genes associated with cocaine intake respond to contextual information in a region-specific manner. This comprehensive picture of transcriptome-wide regulation by cocaine SA and WD throughout the brain’s reward circuitry provides new insight into the molecular basis of cocaine addiction, which will guide future studies of the key molecular pathways involved.
2018-08-22 | GSE110344 | GEO
Project description:Neuronal alternative splicing is a key gene regulatory mechanism in brain. Yet the spliceosome machinery is insufficient to fully specify splicing complexity. In considering the role of the epigenome in activity-dependent alternative splicing, we and others find the histone modification, H3K36me3, to be a putative splicing regulator. In the current study, we found that mouse cocaine self-administration caused widespread differential alternative splicing, concomitant with enrichment of H3K36me3 at differentially spliced junctions. Importantly, only targeted epigenetic editing can distinguish between a direct role of H3K36me3 in splicing and an indirect role via regulation of splice factor expression elsewhere on the genome. We targeted Srsf11, which was both alternatively spliced and H3K36me3 enriched in brain following cocaine self-administration. Results: Epigenetic editing of H3K36me3 at Srsf11 was sufficient to drive its alternative splicing and enhanced cocaine self-administration, establishing the direct causal relevance of H3K36me3 to alternative splicing of Srsf11 and to reward behavior.
2021-07-31 | GSE180988 | GEO
Project description:Chromatin-mediated alternative splicing regulates cocaine reward behavior
| PRJNA750320 | ENA
Project description:The ventral pallidum (VP) was defined as a basal ganglia nucleus and a major output of the nucleus accumbens. It is known to be involved in motivated behaviors, including feeding. We sought to further characterize VP by sequencing the RNA from individual nuclei in mouse and rat VP and analyzing neuronal expression patterns. We also investigated the impact of a high-fat diet on VP transcription. These data will be useful for understanding cell type diversity in VP, homology between mouse and rat VP, and the impact of diet on VP gene expression.
2025-10-07 | GSE262729 | GEO
Project description:The ventral pallidum (VP) is critical for motivated behaviors. While contemporary work has begun to elucidate the functional diversity of VP neurons, the molecular heterogeneity underlying this functional diversity remains incompletely understood. We used snRNA-seq and in situ hybridization to define the transcriptional taxonomy of VP cell types in mice, macaques, and baboons. We found transcriptional conservation between all three species, within the broader neurochemical cell types. Unique dopaminoceptive and cholinergic subclusters were identified and conserved across both primate species but had no homolog in mice. This harmonized consensus VP cellular atlas will pave the way for understanding the structure and function of the VP and identified key neuropeptides, neurotransmitters, and neuro receptors that could be targeted within specific VP cell types for functional investigations.
2024-10-30 | GSE277465 | GEO