Cell type-specific transcriptional programs in mouse prefrontal cortex during adolescence and addiction

Aritra Bhattacherjee,Renchao Chen,Yi Zhang,Wenqiang Chen,Mohamed Nadhir Djekidel,Luis M Tuesta

doi:10.1038/s41467-019-12054-3

Aritra Bhattacherjee, Renchao Chen + Show 4 more

Open Access

https://doi.org/10.1038/s41467-019-12054-3

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Abstract

Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors. Yet, the specific transcriptional programs in each neuron subtype remain unknown. Using single-cell RNA sequencing (scRNA-seq), here we comprehensively classify all unique cell subtypes in the PFC. We analyze transcriptional dynamics of each cell subtype under a naturally adaptive and an induced condition. Adaptive changes during adolescence (between P21 and P60), a highly dynamic phase of postnatal neuroplasticity, profoundly impacted transcription in each neuron subtype, including cell type-specific regulation of genes implicated in major neuropsychiatric disorders. On the other hand, an induced plasticity evoked by chronic cocaine addiction resulted in progressive transcriptional changes in multiple neuron subtypes and became most pronounced upon prolonged drug withdrawal. Our findings lay a foundation for understanding cell type-specific postnatal transcriptional dynamics under normal PFC function and in neuropsychiatric disease states.

Highlights

Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors
These results indicate that PFC has neuron populations that are transcriptionally distinct from its closest (ALM), as well as farthest (VISp) neighbors, which may explain unique functions of the PFC compared to the other cortical regions
As expected in cerebral cortex, we identified 8 broad cell types in PFC (Fig. 1)

Summary

Introduction

Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors. Based on the expression of cell type-specific markers, the non-neuronal cells were clustered as: astrocytes (Gja1+), oligodendrocyte (Aspa+), newly formed oligodendrocytes (Bmp4+), oligodendrocyte precursors (Pdgfra+), microglia (C1qa+) and endothelial cells (Flt1+) (Fig. 1c, d).

Results

Conclusion