?Social odors??sometimes called ?pheromones??are key regulators of infant feeding, reproduction, and aggression. Once detected by the sense of smell, these signals act to modulate the animal's hormonal status. Conversely, steroid metabolites in urine have emerged as one of the best-understood classes of cues detected by the vomeronasal organ, one of the principal sensory organs for pheromones. This tight integration between hormones and olfaction is believed to serve as an ?honest signal? in which information about physiological status is inferred from metabolites of the hormones that control it. In mammals, the identity of most pheromones remains mysterious. In mice, despite 40 years of investigation, the principal sex-specific vomeronasal cues in natural stimuli like urine were controversial or unknown. Recently, my laboratory developed new techniques to perform large scale unbiased screens for the ligands that activate vomeronasal sensory neurons. Using these tools and combining them with neurophysiology, endocrine manipulations, and analysis of behavior, we have identified the first female sex pheromones for the mouse. With support from the NIH, we propose to identify most or all of the male-specific urinary cues that activate the vomeronasal organ. Specifically, we propose to (1) purify male-specific ligands; (2) solve their chemical structures, and (3) identify their pattern of expression and contributions to two behaviors, the Vandenbergh Effect (puberty acceleration) and the Bruce Effect (pregnancy block).
These aims promise to open new doors in our understanding of the relationship between sex, olfaction, hormones, and behavior.

Public Health Relevance

Hormones are powerful regulators of health, mood, and behavior, yet much remains unknown about how sensations and experiences regulate hormones. Mice, through their sense of smell, provide a tractable model for studying how sensory perception regulates behavior and hormonal status, and may provide new insights into the sensory regulation of the timing of puberty and miscarriage. We propose to identify the core stimuli and neuronal mechanisms by which the sense of smell influences hormones and behavior.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC010381-10
Application #
9952346
Study Section
Neuroendocrinology, Neuroimmunology, Rhythms and Sleep Study Section (NNRS)
Program Officer
Sullivan, Susan L
Project Start
2009-09-30
Project End
2021-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
10
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Washington University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Xu, Pei Sabrina; Lee, Donghoon; Holy, Timothy E (2016) Experience-Dependent Plasticity Drives Individual Differences in Pheromone-Sensing Neurons. Neuron 91:878-892
Fu, Xiaoyan; Yan, Yuetian; Xu, Pei S et al. (2015) A Molecular Code for Identity in the Vomeronasal System. Cell 163:313-23
Hammen, Gary F; Turaga, Diwakar; Holy, Timothy E et al. (2014) Functional organization of glomerular maps in the mouse accessory olfactory bulb. Nat Neurosci 17:953-61
Arnson, Hannah A; Holy, Timothy E (2013) Robust encoding of stimulus identity and concentration in the accessory olfactory system. J Neurosci 33:13388-97
Tolokh, Illya I; Fu, Xiaoyan; Holy, Timothy E (2013) Reliable sex and strain discrimination in the mouse vomeronasal organ and accessory olfactory bulb. J Neurosci 33:13903-13
Turaga, Diwakar; Holy, Timothy E (2012) Organization of vomeronasal sensory coding revealed by fast volumetric calcium imaging. J Neurosci 32:1612-21
Meeks, Julian P; Arnson, Hannah A; Holy, Timothy E (2010) Representation and transformation of sensory information in the mouse accessory olfactory system. Nat Neurosci 13:723-30