Dopaminergic short axon cells integrate sensory and top-down inputs to enhance discriminative learning in the mouse...

Discriminative learning enhances contrast between sensory inputs to allow fast and accurate decision-making. However, the neural mechanisms that selectively enhance sensory representations to improve discrimination remain unclear. Here, we show that learning-induced differential gating of olfactory inputs takes place at the first stage of sensory processing in the mouse olfactory bulb and requires dopaminergic short axons cells (SACs). Optical imaging, spatial transcriptomics, and electron microscopy experiments reveal that synaptic and structural plasticity in SACs allows odor valence-based modulation of their interactions with other cell types in the olfactory glomeruli. Importantly, an increase in tyrosine hydroxylase expression by SACs surrounding responding glomeruli, with a bias towards those activated by reward odors, creates a valence-based modulation of sensory input. Further, we identify cholinergic input from the horizontal limb of the diagonal band as the valence-dependent signal that modulates SAC activities and refines sensory representation via disinhibition. Our findings reveal a circuit mechanism where an interneuron population serves as a central hub integrating sensory input and top-down signal to enhance sensory acuity.