Figure 1. Inhibition of the mAON enhances olfactory sensitivity and the performance of olfaction-dependent behaviours.

(a) AAV-mediated expression of hM4D-mCherry in CaMKIIa-positive neurons was restricted to the mAON. ITR, inverted terminal repeats. (b, left) Serial sections depicting the extent of hM4D-mCherry expression at viral infusion site with AP axis coordinates from bregma for reference. (right) Confocal images of OB coronal sections depicting DAPI-stained nuclei and mCherry-positive axon fibres arriving from mAON. Right panels correspond to the boxed regions in the left panel. mCherry-positive axon terminals of mAON CaMKIIa-positive neurons were found to innervate primarily the deep granule cell layer with a few scattered fibres present in the glomerular layer of the OB (EPL, external plexiform layer; GCL, granule cell layer; GL, glomerular layer; IPL, internal plexiform layer; MCL, mitral cell layer; ONL, olfactory nerve layer), but virtually none are present in the anterior (above) or posterior piriform cortex (below). (c) CNO treatment did not alter investigation of mineral oil (0% odour concentration) across habituation trials (inset; data obtained from olfactory habituation/dishabituation test, Supplementary Fig. 2a), but increased investigation time of an odour at a low concentration compared with vehicle treatment (n=11, two-way ANOVA interaction F_(2,20)=10.94, *P<0.001). (d) CNO treatment decreased the latency to locate a buried food reward (n=12, paired-samples t-test, t₍₁₁₎=2.85, *P<0.05). (e) Compared with vehicle-treated mice, CNO-treated mice spent proportionally more time investigating a conspecific versus an empty cage (n=11 per group, independent-samples t-test, t₍₂₀₎=6.32, *P<0.001; absolute investigation time for novel conspecific between groups, t₍₂₀₎=2.15, *P<0.05), and showed a higher preference for investigating a novel versus familiar conspecific (t₍₂₀₎=2.18, *P<0.05; absolute investigation time for novel conspecific between groups, t₍₂₀₎=6.27, *P<0.05). ANOVA, analysis of variance.