2025 Theses Doctoral

The Nose Knows: Understanding the molecular underpinnings of learning and adaptation through the main olfactory epithelium

Stecky, Beka

In order to survive, an animal must adapt to an often-dangerous environment. Natural environments are replete with sensory information that the animal must interrogate and respond to. One class of sensory information is odors. Odors are small volatile molecules that provide information about a range of environmental states, such as potential food, mates, and predators. In turn, olfaction guides adaptive behaviors.

We use the mouse olfactory system to probe how the animal adapts to salient stimuli. We use a behavioral conditioning paradigm called olfactory fear conditioning to teach the mouse to associate a specific odor with a aversive shock stimulus. Odor-shock pairing induces measurable changes in olfactory-guided behavior and in the physiology of the main olfactory epithelium (MOE), the primary sensory tissue of the olfactory system.

Odor-shock pairing induces robust odor aversion. This behavioral phenotype is coupled with transcriptional changes in the MOE that reflect two main adaptations in neuronal tissue: First, odor-sensing neurons become primed to sense the conditioned odor. Second, the identity of odor-sensing neurons becomes biased toward expressing the conditioned odor’s receptor. All in all, odor-shock pairing produces a physiological state that prepares the animal for future odor activity, which in turn facilitates adaptive behavior. This work provides insight into the molecular underpinnings of learning and adaptation, suggesting that sensory tissue itself can harbor experiential memory.