The sense of smell in animals can strongly influence feeding and social behaviors. In order to accomplish these tasks, all the events starting from the detection of odorants by olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) must be properly tuned in terms of amplitude and kinetics. After the odorant binding to its receptor, a series of events leads to the activation of adenylyl cyclase III that produces cAMP that in turn opens the cyclic nucleotide-gated channels causing a first depolarizing current mediated by Na⁺ and Ca²⁺ entry. In addition, the increase of the intracellular Ca²⁺ concentration activates the TMEM16B channel providing a further amplification of the odorant response. Since its relatively recent characterization in the OE, the contribution of TMEM16B to the amplitude and kinetics of the odor transduction process is still puzzling. We investigated the role of TMEM16B in odorant-induced responses using electro-olfactograms, that record the summated generator potential of the OSN population. Surprisingly, we found that the odorant responses were bigger in Tmem16b knock-out (KO) than in wild-type (WT) mice. In addition, the lack of TMEM16B altered the kinetics of the response that had a faster rising phase and shorter recovery time in the KO. To investigate response adaptation we used a double pulse protocol with different inter-pulse intervals and found that the recovery from adaptation at high odorant concentration was faster in KO than in WT mice. In another adaptation paradigm we applied an odorant conditioning stimulation followed by test pulses with different odorant concentrations. We found that the amplitude of the responses to the test stimulations was significantly smaller in WT whereas no significant difference was found in KO mice showing that TMEM16B plays an important role in the molecular mechanisms that mediate OSNs adaptation.
This work was funded by the Italian Ministry of Education, University and Research.