The proposed experiments use the mouse olfactory system as a model to understand how neurons restore functional connections to their targets in the central nervous system after massive neuronal loss and subsequent regeneration. The mammalian olfactory system has the remarkable capacity for regeneration and regrowth of its primary sensory neurons (olfactory sensory neurons) after even a complete loss. However, the regrowth of sensory neuron axons to their appropriate targets in the brain - the glomeruli of the olfactory bulb - appears to be imperfect, with many axons contacting inappropriate glomeruli. The proposed experiments will, for the first time, ask how this mistargeting alters the glomerular maps of activity that normally represent odor information. A genetically-encoded indicator of olfactory sensory neuron activation will be used to compare odorant representations in normal and epithelial lesion-recovered mice. In parallel, histological analysis of the retargeting of a single, molecularly-identified receptor type will permit a detailed anatomical analysis of this phenomenon. Experiments are proposed which a) investigate the time-course of regeneration of glomerular activity maps and the precision with which they recover after lesion; b) test whether the precision of sensory neuron retargeting depends on odorant-evoked activation of the neurons; and c) investigate the relationship between the odorant response properties of olfactory sensory neurons and their choice of glomerular target. The experiments should generate the first general picture of the extent to which functional representations of odors are altered after lesion and recovery, and point to mechanisms by which connections between olfactory neurons and their targets are reformed. Errors in the reinnervation of glomeruli are likely mechanisms underlying olfactory dysfunction in humans recovering from olfactory loss due to trauma or infection. These experiments may provide improved cellular-level explanations for such clinical deficits and could suggest therapeutic strategies. More generally, reestablishing appropriate neural connectivity is a prerequisite for the full recovery of function of any sensory or motor system. For example, incorrect connections to the CMSafter recovery of peripheral nerve fibers can cause hyperalgesia and other neuropathies. This work could potentially yield insight into treatment strategies for these and other syndromes related to inappropriate neuronal connections.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC008116-03
Application #
7383780
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Davis, Barry
Project Start
2006-04-01
Project End
2010-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
3
Fiscal Year
2008
Total Cost
$297,771
Indirect Cost
Name
Boston University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Cheung, Man C; Jang, Woochan; Schwob, James E et al. (2013) Functional recovery of odor representations in regenerated sensory inputs to the olfactory bulb. Front Neural Circuits 7:207
Cheung, Man Ching; Carey, Ryan M; Wachowiak, Matt (2009) A method for generating natural and user-defined sniffing patterns in anesthetized or reduced preparations. Chem Senses 34:63-76