Cholinergic feedback for modality- and context-specific modulation of sensory representations

The brain's ability to prioritize sensory information is crucial for adaptive behavior, yet its mechanisms remain unclear. We investigated basal forebrain cholinergic neurons modulating olfactory bulb (OB) circuits in mice. The activity of cholinergic feedback axons in OB correlated with orofacial movements, with little responses to passively experienced odors. When mice engaged in an olfactory task, OB cholinergic axons rapidly shifted their response patterns from movement correlated to odor aligned. This response shift was absent in cholinergic axons projecting to the dorsal cortex during olfactory task engagement, and in OB, during an auditory task. Inactivation of OB-projecting cholinergic neurons impaired olfactory task performance and reduced odor responses in OB granule cells. Thus, the cholinergic system dynamically modulates sensory processing in a modality-specific and context-dependent manner.