STIMULUS-DRIVEN MODULATION OF SENSORY SENSITIVITY IN THE MOUSE OLFACTORY PERIPHERY

Fast, short-term sensory adaptation to prolonged or repetitive stimuli is essential for maintaining dynamic sensitivity in sensory systems. In olfactory sensory neurons (OSNs), odorant receptor (OR) activation triggers a G-protein-mediated cAMP cascade, which is counterbalanced by Ca²⁺/calmodulin-dependent negative feedback. Given the high ligand affinity of ORs, many OSNs exhibit very low odorant detection thresholds, resulting in sensitivity ranges spanning several orders of magnitude. However, it is unclear whether mechanisms of sensitivity modulation extend beyond adaptation and whether such modulation depends on stimulus concentration.
Here, using patch-clamp recordings from mouse OSNs in acute slices of the nasal cavity, we investigate how varying interstimulus intervals and stimulus intensities modulate action potential generation, determining olfactory signal transmission to the brain. We dissect (i) which and (ii) how concentrations are de- and encoded in the olfactory periphery, (iii) which types of modulation occur, (iv) which signaling cascade stages play important roles in modulation, and (v) whether dose-dependent modulation is OR-dependent. Together, we seek to understand how OSNs fine-tune their sensitivity and responsiveness to represent a wide range of odorant concentrations.