A limitation in the capacity of the peripheral olfactory system to reconstitute completely or reconnect correctly following insult could determine the degree of dysfunction and whether it persists. Previously, we used an interdisciplinary approach to document a capacity for recovery of the system anatomically (reconstitution of the epithelium and reinnervation of the bulb) and functionally (restoration of an odorant identification task and reestablishment of optically recorded mucosal activity patterns). However, the time course for both behavioral and electrophysiological recovery lagged that for anatomical recovery (using such measures as GAP-43 expression, OMP-expression, basal cell proliferation and re-innervation with the bulb). Although the recovered system demonstrated a capacity to support function, the question as to whether the perception of odorant quality has been changed as a function of damage and recovery still remains. Using the same interdisciplinary approach we propose to; 1) further define the relationship between time post-lesion and the preparedness of the olfactory system to support criterion level performance on an odorant identification task; 2) test the hypothesis that odor ant quality identification is preserved following reconstitution of the system; 3) determine whether and when bulbar electrophysiological activity patterns recover, and determine the correspondence between the neurophysiological recovery of the mucosa and bulb; and 4) assess, using anatomical and immunochemical techniques, metabolic activation of the bulb and expression of c-fos in response to odorants. The anatomical assessments of recovery will be related in time register to the behavioral and neurophysiological recovery process. We also propose to investigate whether and how partial destruction of either the olfactory mucosa or olfactory bulb can disrupt odorant quality coding. Clinical observations suggest that deficits can be either global or specific to a subset of odorants, in patients with peripheral or central damage. We previously observed that ethyl bromide lesioned rats, retaining as little as 5% of the normal complement of olfactory epithelium, functioned at a hyposmic level on an odorant identification task. More importantly, one of two condition of hyposmia did exist, namely, a deficit in performance across all odorants of the identification task or a deficit restricted to some subset. These clinical and experimental observations raise the question as to how much epithelium is required to support normal function, and is there a relationship between the area damaged and the odorants on which performance is lost. We propose to examine whether and to what degree the pattern of behavioral deficit on an odorant identification task is related to the extent and pattern of epithelial destruction. Similarly, using 2-DG patterns of activation as our guide, we will examine the degree to which focally restricted lesions of the olfactory bulb will result in selective odorant identification deficits. These studies will refine our understanding of the capacity of the olfactory system to recover following peripheral lesions. Further, they will provide insights into the importance of spatial activation at the level of the olfactory mucosa and bulb. As a result, we will better understand the relationship between damage to these structures and the functional manifestation.
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