been used successfully in the investigation of several different processes in which the complexity of the molecular interactions challenges their understanding through classical reductionist approaches. Among these processes is the olfactory transduction and adaptation, two key cellular events involved in odorant reception and in its consequences for finding food, avoiding predators, identifying sexual partners and other relevant aspects of animal survival. The olfactory information is transmitted through the signaling pathways located in the cilia of olfactory sensory neurons. Odorants bind to G protein coupled receptors triggering the activation of Gaolf that in turn activates adenylate cyclase 3 producing cyclic adenosine monophosphate . Molecules of cAMP bind to cyclic nucleotide-gated channels promoting their opening and allowing cations, mainly sodium and calcium ions, to flow to the intracellular medium depolarizing the cell. This transient increase of the intracellular Ca2+ concentration opens Ca2+-activated chloride channels that amplify the CNG channel signal. The OSN adapts after a previous exposure to stimulus. Shortterm adaptation is defined as a decrease in responsiveness to the odor presentation that occurs PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19661824 within a few seconds after a brief conditioning stimulus. Previous works have shown that STA is 1 Regulation of Transduction and Adaptation induced by a brief odor pulse, has a recovery time of seconds, and can be abolished by the removal of intracellular Ca2+. Moreover, experimental and theoretical evidences have demonstrated that STA happens at the level of CNG channel and presumably is independent of the activity of phosphodiesterases, which hydrolyze cAMP terminating its action. However, Ca2+-dependent mechanisms involving PDEs may act by modulating the concentration of cAMP with consequences for STA. Additionally, Ca2+/Calmodulin can bind to CNG channels, promoting a decrease in its affinity to cAMP, a process that seems to be involved in STA. Since cAMP opens CNG channels leading to Ca2+ influx that induces STA, Ca2+ extrusion mainly through Na+/Ca2+ and K+ exchangers and, possibly, plasma membrane Ca2+-ATPases leads to the resetting the cellular resting state. There are evidences that K+-independent Na+/Ca2+ exchangers and NCKX are TG100 115 site present in mammalian OSNs. Another mechanism controlling intracellular concentrations of cAMP is the internalization of GPCRs mediated by phosphorylation catalyzed by cAMP-dependent protein kinase and G-protein-coupled receptor kinase 3 , but the specific role of GPCR cycling in the occurrence of STA is unknown. In addition, although cAMP and Ca2+ are involved in STA, it is uncertain how their regulation by distinct signaling pathways affects the recovery times of OSN responses to odorants. The decrease in OSN sensitivity can occur not only in the presence of a brief conditioning stimulus, but also 
in the presence of a prolonged stimulus. The decline in OSN response produced by a sustained odor pulse is defined as desensitization. The molecular mechanism behind the occurrence of DS likely act upstream of cAMP production and involves Ca2+ dependent pathways. The present study uses pharmacological manipulation of signaling pathways involved in STA accessed by electro-olfactogram responses to paired pulses of odorant to investigate the action of PDE, PKA, and vesicle internalization and recycling in the fine control of olfactory adaptation. In addition, we have developed a stochastic kin
