Functional architecture of the forebrain cholinergic system in rodents

Abstract The basal forebrain 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. To better understand the underlying organization principles of the BFCS, more and higher quality anatomical data and analysis is needed. Here, we created a “virtual Basal Forebrain”, combining data from numerous rats with cortical retrograde tracer injections into a common 3D reference coordinate space and developed a “spatial density correlation” methodology to analyze patterns in BFCS cortical projection targets, revealing that the BFCS is organized into three principal networks: somatosensory-motor, auditory, and visual. Within each network, clusters of cholinergic cells with increasing complexity innervate cortical targets. These networks represent hierarchically organized building blocks that may enable the BFCS to coordinate spatially selective signaling, including parallel modulation of multiple functionally interconnected yet diverse groups of cortical areas.