The olfactory system provides a unique window into how genetically defined neuronal circuits give rise to normal brain function. Volatile odorants are detected by a large family of olfactory receptor genes, each of which is represented by a specific functional input to the brain. Progress towards understanding mammalian olfaction has been hindered by difficulties in identifying main olfactory receptor genes that contribute significantly to odor perception. This proposal addresses how individual members of a small main olfactory receptor family, the Trace Amine-Associated Receptors (TAARs), contribute to odor perception in mammals. The TAARs are conserved in humans, mice and other vertebrates suggesting an important function. We propose a combination of genetics, physiology and behavior to test the hypothesis that the TAARs are the most sensitive receptors in a distinct pathway that mediates innate aversion to amines-a biologically relevant class of odorants that are produced by decay and microbial action.
Specific Aim 1 is to determine whether the TAARs contribute significantly to setting behavioral detection thresholds to amines.
Specific Aim 2 is to determine whether selective activation of TAAR inputs can drive aversive behaviors.
Specific Aim 3 is to determine whether remapping the location of TAAR inputs to the olfactory bulb alters odor perception. Achieving these aims will advance our understanding of how this novel chemosensory gene family contributes to olfaction, and how the organization of mammalian olfactory circuits influences odor perception in mammals, including humans.

Public Health Relevance

The olfactory system allows humans to evaluate the quality of food sources and to avoid harmful chemicals, thereby promoting overall health and quality of life. We are using a combination of genetics, physiology and behavior to understand how a specific class of chemosensory receptors allows mammals to detect amines-a biologically important class of perceptually aversive chemicals that are produced by decay and microbial activity. Experiments described in this proposal will test whether individual receptors contribute significantly to amine sensitivity, and whether the organization of olfactory inputs dictates innat odor responses.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC013576-05
Application #
9511591
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2014-07-15
Project End
2019-06-30
Budget Start
2018-07-01
Budget End
2019-06-30
Support Year
5
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Arneodo, Ezequiel M; Penikis, Kristina B; Rabinowitz, Neil et al. (2018) Stimulus dependent diversity and stereotypy in the output of an olfactory functional unit. Nat Commun 9:1347