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 to the nervous system, it seems likely that sensory receptor cells would evolve compensatory responses to sensory deprivation. In fact, recent evidence suggests that neurons in many areas of the nervous system display 'homeostaticplasticity' such that their intrinsic excitability is altered by experience. In the developing olfactory system, 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, it was discovered that adenylyl cyclase three (ACIII), Olfactory Marker Protein (OMP), and a phopshodiesterase (PDE4A), all proteins known to play a role in olfactory transduction, increase in concentration in olfactory receptor neurons following sensory deprivation. These results imply that olfactory receptors, like many other neurons, have a compensatory response to stimulus deprivation. To further evaluate this hypothesis, the PI and collaborators will: (1) use immunocytochemistry and Western blotting for OMP, PDE4A, ACIII, and other transductory elements to confirm and extend preliminary findings, (2) compare electro-olfactograms (EOGs) recorded from olfactory receptor neurons on the occluded and non-occluded sides of the nasal cavity, and (3) measure the psychophysical capabilities of mice that have undergone olfactory deprivation by naris occlusion. Taken together, the results of these studies will help establish a previously unknown compensatory plasticity in the olfactory system, shed light on the role of OMP, PDE4A, and other proteins involved in odor transduction, and clarify the roll of experience in the developing and adult olfactory system. In addition to their inherent intellectual merits, the proposed activities are designed to have a broader impact in that they will enhance the culture of science at Randolph-Macon College, a small liberal arts institution, by increasing the opportunities for students to participate in independent research. Also, this award will improve the College's research infrastructure by providing equipment that will be foundational for an emerging undergraduate research initiative. This grant is part of a major thrust by the College's Science Division to revise the science curriculum such that student learning is more hands-on, open-ended, and interdisciplinary. Proposed activities to improve the culture of science are focused on graduate and medical school bound students but will also be of interest to other science and non-science majors. Students completing independent research projects will use the requested equipment and will benefit from the requested summer stipends, funds for supplies, and funds for meeting attendance. In addition to the broader impact at Randolph-Macon, this award will allow the PI and participating college students to improve the college preparation of a group of inner-city high school students and, hopefully, increase the number of qualified college-bound minority students in the pipeline. Lastly, this award will foster collaborations between Randolph-Macon College, targeted inner-city schools, and a regional research center, Virginia Commonwealth University.
