The peripheral mammalian olfactory epithelium is a dynamic tissue that contains stem cells capable of generating new sensory neurons in response to injury or pathology. We have recently determined that this regenerative capacity remains robust even in very old animals. This raises several critical questions about the olfactory system and its unique capacity to regenerate neurons. Are these older stem cells capable of generating normal functioning neurons? How do they determine which receptor genes to express, as these differ at different stages of an animal's life? How do these new neurons integrate into an older established tissue and the existing circuitry of the olfactory bulb? We have proposed to use a genetic strategy in which the Diphtheria toxin receptor is expressed specifically in OMP+ mature olfactory sensory neurons. Upon injection of the diphtheria toxin only those cells expressing the receptor will be killed, resulting in a lesion of the OSN population with little or no collateral damage to other cells in the epithelium or in the target olfactory bulb. This allows us to examine the re-growth of a new neuroepithelium in an otherwise normal, but older animal. These experiments will provide insight into the tissue aging process and into the reconstitution of a new olfactory system in aged animals. We hope to gain an understanding of neuronal proliferation that will allow us to imagine ways to compensate for neurodegenerative losses in numerous pathologies and over the course of normal aging. Additionally it may suggest strategies for improving the olfactory sense in the aged, thereby reversing the poor nutrition and quality of life common to this population.

Public Health Relevance

This proposal seeks to establish the nature of adult neuronal stem cell renewal. These experiments will provide insight into the stem cells'developmental program and the tissue aging process. Research in this area may help to address two problems;first, it may aid in our understanding of how to encourage neuronal proliferation or alter synaptic plasticity in order to compensate for losses due to neurodegenerative diseases, and second, it might help to reverse the poor nutrition and eating habits often seen in the elderly due to olfactory dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC012567-02
Application #
8610287
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2013-02-01
Project End
2018-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
2
Fiscal Year
2014
Total Cost
$302,894
Indirect Cost
$111,644
Name
Columbia University (N.Y.)
Department
Biology
Type
Other Domestic Higher Education
DUNS #
049179401
City
New York
State
NY
Country
United States
Zip Code
10027