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bioRxiv · 10.1101/2025.05.09.653136

Brain-wide cell-type-specific noradrenergic modulation of the transcriptome

Slater, C.·Lantin, T.·Wellman, S.·Jia, L.·Gonzalez, G.·McFaline-Figueroa, J. L.·Wang, Q.
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Abstract

Neuromodulatory systems such as the locus coeruleus-norepinephrine (LC-NE) system exert a widespread influence on brain function, yet the transcriptional consequences of such neuromodulatory perturbations remain largely unknown across the many unique cell types in the brain. In this study, we establish a generalizable framework to map brain-wide, cell-type-specific gene expression changes in mice following in vivo chemogenetic activation or inhibition of LC neurons. Single-nucleus RNA sequencing revealed that LC perturbation induces widespread but highly cell type- and region-specific transcriptional program changes, shaped by the distribution of adrenergic receptor subtypes. These findings support a model in which a shared global signal of neuromodulatory tone can produce discrete, context-dependent cellular outcomes through distinct molecular gating mechanisms of cell-type-specific adrenergic receptor subtype combinations. By establishing gene expression as a quantifiable metric of neuromodulatory control, this study lays the foundation for transcriptionally informed interventions capable of modulating brain functions with cellular precision.

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Slater, C., Lantin, T., Wellman, S., Jia, L., Gonzalez, G., McFaline-Figueroa, J. L., Wang, Q.. 2025-05-10. Brain-wide cell-type-specific noradrenergic modulation of the transcriptome. https://doi.org/10.1101/2025.05.09.653136

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