Back

Transcriptional and functional profiles of muscarinic receptor-expressing neurons in primate lateral prefrontal and anterior cingulate cortices

Tsolias, A.; Mojica, C. A.; Yamani, R.; Khanna, S. D.; Abdullatif, S. A.; Snyder, B. J.; Chang, W.; Guillamon-Vivancos, T.; Goodliffe, J.; Capriglione, A. L.; Palanca, I. L. T.; Martinez, J.; Campbell, J. D.; Luebke, J. I.; Zeldich, E.; Medalla, M.

2025-05-24 neuroscience
10.1101/2025.05.23.655820 bioRxiv
Show abstract

Acetylcholine modulates anterior cingulate (ACC) and lateral prefrontal (LPFC) cortices for cognitive-motivational integration, via specific m1-m4 muscarinic receptors (mAChR) encoded by CHRM1-4 genes. Single-nucleus RNA sequencing and mRNA-protein histology in macaques revealed CHRM3 to be the most enriched mAChR gene in neurons, while m1 predominates at the protein level, likely due to nuclear retention of CHRM3 and cytoplasmic trafficking of CHRM1. CHRM3 and CHRM1 showed strong co-expression and functional overlap, and were transcriptomically-distinct from CHRM2, which was uniquely enriched in deep layer excitatory and PVALB+ inhibitory neurons. Although CHRM+ cell distributions were similar between areas, CHRM1-3+ excitatory neurons in ACC exhibited upregulation of synaptic plasticity genes relative to LPFC. Functional in vitro experiments confirm a more robust cholinergic-mediated decrease in excitatory:inhibitory synaptic ratio in ACC than in LPFC neurons, accompanied by compensatory changes in spine morphology. These findings highlight region-specific acetylcholine signaling essential for flexible processing, learning and memory.

Published in Communications Biology (predicted rank #7) · training set

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.