Neural activity, either sensory driven or endogenous, is critical for the development and functional maintenance of many parts of the nervous system. For example, if sensory input is eliminated during a critical period in early life, primary sensory areas in the brain can be malformed, sometimes irreversibly. Given the importance of continued sensory input, it is possible that sensory receptor cells would evolve compensatory responses to sensory deprivation. Recent evidence suggests that neurons in many areas of the nervous system do indeed display homeostatic plasticity such that their overall intrinsic excitability is altered by experience. In the developing olfactory system, surgically occluding one side of the nasal cavity, and thus reducing odor stimulation to olfactory receptor neurons, alters the development of olfactory pathways receiving input from these receptors. Recently, the PI and his colleagues discovered that adenylyl cyclase three (ACIII), olfactory marker protein (OMP), and a phosphodiesterase (PDE4A), all proteins known or suspected to be involved in olfactory transduction or modulation, increase in concentration in olfactory receptor neurons following naris occlusion. These results imply that olfactory neurons, like many other neuron types, have a compensatory response to stimulus deprivation. The funds made available by the NSF will allow the PI to further evaluate this hypothesis. Specifically, electrophysiological equipment will be purchased to allow a comparison between the responses of normal and deprived olfactory sensory cells. If Dr. Coppola's hypothesis is correct, deprived cells should become more responsive to odors. An operant chamber and flow-dilution olfactometer will be purchased to allow behavioral odor thresholds (and other parameters) to be compared between normal and deprived mice. According to his hypothesis, mice deprived of odors should have a decreased threshold compared to control mice as a consequence of their compensatory response. Lastly, consumable supplies will be purchased that will allow preliminary immunocytochemical work on the ACIII, OMP, PDE4A to be confirmed and extended. Taken together the results of these studies will help establish a previously unexplored compensatory mechanism of olfactory receptor neurons, shed light on the role of OMP and PDE4A in odor transduction/modulation and clarify the role of odor deprivation on the developing and adult olfactory system. The broader impact of this project lies in its ability to improve the science infrastructure at Randolph-Macon College.
