Cell-type specific transcriptional adaptations of nucleus accumbens interneurons to amphetamine.
Mol Psychiatry
; 28(8): 3414-3428, 2023 Aug.
Article
em En
| MEDLINE
| ID: mdl-35173267
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Anfetamina
/
Estimulantes do Sistema Nervoso Central
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article