Nonlinear high-activity neuronal excitation enhances odor discrimination

Discrimination between different signals is crucial for animals' survival. Inhibition that suppresses weak neural activity is crucial for pattern decorrelation. Our understanding of alternative mechanics that allow efficient signal classification remains incomplete. We show that Drosophila olfactory receptor neurons (ORNs) have numerous intraglomerular axo-axonal connections mediated by the G protein-coupled receptor (GPCR), muscarinic type B receptor (mAChR-B). Contrary to its usual inhibitory role, mAChR-B participates in ORN excitation. The excitatory effect of mAChR-B only occurs at high ORN firing rates. A computational model demonstrates that nonlinear intraglomerular or global excitation decorrelates the activity patterns of ORNs of different types and improves odor classification and discrimination, while acting in concert with the previously known inhibition. Indeed, knocking down mAChR-B led to increased correlation in odor-induced ORN activity, which was associated with impaired odor discrimination, as shown in behavioral experiments. Furthermore, knockdown (KD) of mAChR-B and the GABAergic GPCR, GABAB-R, has an additive behavioral effect, causing reduced odor discrimination relative to single-KD flies. Together, this study unravels a novel mechanism for neuronal pattern decorrelation, which is based on nonlinear intraglomerular excitation.