Cell-type and sex-specific rhythmic gene expression in the nucleus accumbens

Area of Science:

• Neuroscience
• Chronobiology
• Genomics

Background:

• Circadian rhythms are vital for health, with disruptions linked to diseases like psychiatric disorders.
• Previous research implicates circadian genes in nucleus accumbens (NAc) neuron behavior, specifically dopamine D1-expressing medium spiny neurons (MSNs).
• Diurnal transcript expression rhythms within NAc MSNs remain largely uncharacterized.

Purpose of the Study:

• To identify and characterize diurnal rhythmic transcripts in D1- and D2-expressing NAc neurons.
• To compare these rhythms with those in NAc homogenate and astrocyte samples from male and female mice.
• To investigate sex differences in transcript rhythmicity and associated biological pathways.

Main Methods:

• Single-cell RNA sequencing was used to analyze transcript expression in D1-MSNs, D2-MSNs, and astrocytes from the NAc of male and female mice.
• Rhythmic transcripts were identified using bioinformatics algorithms.
• Pathway enrichment analysis was performed to understand the functions of rhythmic genes.

Main Results:

• All analyzed cell types (D1-MSNs, D2-MSNs, astrocytes) exhibit diurnal transcript rhythms.
• Core clock genes show similar peak expression times across cell types and sexes.
• Clock-controlled transcripts display sex-specific peak expression, with females showing a delay, potentially affecting reward pathways.
• Pathway enrichment analysis revealed cell-type and sex-specific differences in rhythmic gene functions.
• Key markers for categorizing MSNs were found to be rhythmic, posing challenges for cell-type specific research.

Conclusions:

• The NAc exhibits complex diurnal transcriptomic rhythms across distinct cell types and sexes.
• Sex differences in clock-controlled gene rhythms may underlie sex-specific variations in reward processing.
• The rhythmicity of MSN markers necessitates careful consideration of sampling time in future NAc research.
• This study provides a comprehensive map of NAc cellular rhythms, enhancing our understanding of their role in behavior and disease.