Hierarchical organization of the forebrain cholinergic system in rats

The basal forebrain (BF) cholinergic system (BFCS) participates in functions that are global across the brain, such as sleep-wake cycles, but also participates in capacities that are more behaviorally and anatomically specific, including sensory perception. However, how it orchestrates all the diverse local and global functions remains to be understood. To uncover the underlying organization principles, we combined data from rat brains by tracing projections from the BF to cortical areas and analyzed spatial-numerical relations of neurons to their cortical targets. The combined dataset revealed algorithmically identified and hierarchically organized three principal networks: somatosensory-motor, auditory, and visual, as defined by the sensory modality most predominant within them. These clusters of cholinergic neurons could enable the BFCS to coordinate spatially selective signaling, including the parallel modulation of multiple functionally interconnected yet diverse groups of cortical areas. This previously unseen blueprint of the hierarchy of cholinergic clusters is ready for functional testing.