Cholinergic feedback for context-specific modulation of sensory representations

Abstract The brain’s ability to prioritize behaviorally relevant sensory information is crucial for adaptive behavior, yet the underlying mechanisms remain unclear. Here, we investigated the role of basal forebrain cholinergic neurons in modulating olfactory bulb (OB) circuits in mice. Calcium imaging of cholinergic feedback axons in OB revealed that their activity is strongly correlated with orofacial movements, with little responses to passively experienced odor stimuli. However, when mice engaged in an odor discrimination task, OB cholinergic axons rapidly shifted their response patterns from movement-correlated activity to odor-aligned responses. Notably, these odor responses during olfactory task engagement were absent in cholinergic axons projecting to the dorsal cortex. The level of odor responses correlated with task performance. Inactivation of OB-projecting cholinergic neurons during task engagement impaired 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, providing a mechanism for a flexible and adaptive sensory prioritization.