Adaptation to prolonged or repetitive stimuli is a critical feature of sensory systems, allowing dynamic adjustment of sensitivity. In olfactory sensory neurons (OSNs), activation of odorant receptors (ORs) and subsequent G-protein-dependent cAMP signaling are balanced by Ca²⁺/calmodulin-dependent negative feedback, resulting in sensory adaptation. Many ORs exhibit high sensitivity with activation thresholds in the low (sub)micromolar concentration range (Firestein et al., 1993; Grosmaitre et al., 2006). Thus, OSN sensitivity spans a range of several orders of magnitude. Whether, beyond adaptation, complementary dose-dependent modulatory mechanisms exist is yet to be identified.
Our pilot Ca²⁺ imaging experiments in dissociated mouse OSNs, using IBMX + forskolin as a "broadband" stimulus, revealed response summation and even potentiation in a dose-dependent manner at short inter-stimulus intervals. With increasing stimulus concentrations, the ratio of OSNs with elevated responses decreased, while the ratio of neurons showing adaptation increased. Here, using patch-clamp recordings from OSNs in acute slices, we investigate (i) which signaling cascade steps/components are modulated during adaptation versus summation processes, (ii) whether dose-dependence is receptor (in)dependent, and (iii) whether the ability to modulate responses is a stable or transient feature of OSNs. Together, we aim to gain insight into how mammalian OSNs shape their odor sensitivity and response strength to cover an extensive range of stimulus concentrations. Moreover, by assessing OSN output, we will learn how signal modulation translates into changes in action potential discharge and, thus, the information conveyed to the brain.