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Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons

ABSTRACT: Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons

PROVIDER: PRJNA751927 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15340700.fastq.gz	Fastqsanger.gz
	SRR15340701.fastq.gz	Fastqsanger.gz
	SRR15340702.fastq.gz	Fastqsanger.gz
	SRR15340703.fastq.gz	Fastqsanger.gz
	SRR15340614.fastq.gz	Fastqsanger.gz

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Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons [ATAC-Seq]

Project description:Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei from the NAc of male and female mice following acute or repeated exposure to amphetamine (AMPH) and sequenced for cell type-specific RNA expression and chromatin accessibility. AMPH regulated the transcription of hundreds of genes in PV+ interneurons, and this program was largely distinct from that regulated in other NAc GABAergic neurons. Chromatin accessibility at enhancers predicted cell-type specific gene regulation, identifying transcriptional mechanisms of differential AMPH responses. Finally, we observed dysregulation of multiple PV-specific, AMPH-regulated genes in an Mecp2 mutant mouse strain that shows heightened behavioral sensitivity to psychostimulants, suggesting the functional importance of this transcriptional program. Together these data provide novel insight into the cell-type specific programs of transcriptional plasticity in NAc neurons that underlie addictive-like behaviors.

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Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons [SingleNucleus-RNA-seq]

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Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons [ATAC-Seq]

Project description:Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons [ATAC-Seq]

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Project description:Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons [SingleNucleus-RNA-seq]

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Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons [Nuclear and Ribo-tag RNA-seq]

Project description:Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons [Nuclear and Ribo-tag RNA-seq]

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Transcriptional alterations in Nucleus Accumbens somatostatin interneurons following exposure to cocaine

Project description:Total RNA-sequencing of FACs isolated nucleus accumbens somatostatin interneuron nuclei Somatostatin interneuron loss in multiple cortical brain regions has been observed postmortem in humans with several neuropsychiatric disorders and their loss is proposed to underlie some common pathological changes in circuit function across numerous syndromes. However, somatostatin interneurons in the nucleus accumbens (NAc), a key brain reward region, remain poorly understood due to the fact that these cells account for <1% of NAc neurons. Here, we used Flouresence activated cell sorting to isolate nuclei of somatostatin-expressing interneurons in the Nucleus Accumbens from individual SST-TLG498 reporter mice that express membrane bound EGFP-F specifically in somatostatin-expressing neurons. We then performed cell-type specific Total RNA-sequencing to characterize the entire transcriptome of NAc somatostatin interneurons after repeated exposure (7 days) to either saline or cocaine. We identified a wide variety of coding and non-coding transcripts that were expressed at high levels and were differentially expressed between saline and cocaine treated mice. Repeated cocaine administration induces transcriptome-wide changes in gene expression within NAc somatostatin interneurons, with particular regulation of transcripts related to neural plasticity. 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 to identify novel neurpathophysiology.

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Chromatin accessibility underlies cell-type specific programs of amphetamine-regulated gene expression in Nucleus Accumbens interneurons

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-06 | GSE181421 | GEO

Transcriptional alterations in Nucleus Accumbens somatostatin interneurons following exposure to cocaine

Project description:Transcriptional alterations in Nucleus Accumbens somatostatin interneurons following exposure to cocaine

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Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine.

Project description:Parvalbumin-expressing (PV+) interneurons of the nucleus accumbens (NAc) play an essential role in the addictive-like behaviors induced by psychostimulant exposure. To identify molecular mechanisms of PV+ neuron plasticity, we isolated interneuron nuclei from the NAc of male and female mice following acute or repeated exposure to amphetamine (AMPH) and sequenced for cell type-specific RNA expression and chromatin accessibility. AMPH regulated the transcription of hundreds of genes in PV+ interneurons, and this program was largely distinct from that regulated in other NAc GABAergic neurons. Chromatin accessibility at enhancers predicted cell-type specific gene regulation, identifying transcriptional mechanisms of differential AMPH responses. Finally, we assessed expression of PV-enriched, AMPH-regulated genes in an Mecp2 mutant mouse strain that shows heightened behavioral sensitivity to psychostimulants to explore the functional importance of this transcriptional program. Together these data provide novel insight into the cell-type specific programs of transcriptional plasticity in NAc neurons that underlie addictive-like behaviors.

| S-EPMC9378812 | biostudies-literature

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