Widespread inhibitory responses in the mouse olfactory sensory neurons in vivo

Odor recognition starts from olfactory sensory neurons (OSNs), but this process is yet to be fully understood in physiological conditions in vivo. Here, we performed two-photon calcium imaging of mouse olfactory sensory neurons in vivo and found that odors produce not only excitatory, but also inhibitory responses at their axon terminals. Robust inhibitory responses at OSN axon terminals remained in two independent mutant mice, in which all possible sources of presynaptic lateral inhibition were eliminated. Therefore, we examined the responses in the olfactory epithelium in vivo, and found robust and widespread inhibitory responses at the level of OSN somata. Moreover, responses to odor mixtures demonstrated extensive mutual modulation (both suppression and enhancement) in OSNs. An in vitro assay demonstrated that some odorants act as inverse agonists to some odorant receptors. The bidirectional nature of OSN responses may be useful for robust odor coding under noisy sensory environment.