The ability to detect and correctly respond to environmental stimuli is critical for survival. Our sense of olfaction enables us to locate food sources, reject food that is spoiled and avoid potential dangers such as hazardous chemicals. It is poorly understood how the brain organizes olfactory information into meaningful representations of the outside world to direct adaptive behavioral responses. To understand how specific olfactory cues can lead to behavior, we will probe the organization of the neural circuits mediating innate, odor- induced aversion in the mouse. Mice exhibit innate avoidance and fear behaviors in response to odors emitted by potentially dangerous predators;these innate behavioral responses are stereotyped in form, suggesting that the neural representations for behaviorally relevant odorants are genetically hard-wired in the mouse.
In Aim 1 we propose to employ a surgical and imaging preparation we have developed in the laboratory to map predator odor-driven neural responses in the olfactory bulb (OB), the first relay of olfactory information in the brain. These experiments will test the hypothesis that all predator odorants activate a small, spatially restricted region of the OB, which would suggest that information for behaviorally important classes of odorants is spatially organized into subdomains of the OB that may mediate innate odor-evoked behavioral responses.
In Aim 2 we propose to interrogate the tuning properties of the primary olfactory sensory neurons (OSNs) - and thus the receptors expressed by those cells - that detect various predator odors by presenting a large odorant set to the mouse and assessing whether the glomeruli that respond to predator odors also respond to any other odorants in the test set. These experiments will provide insight into whether predator odors are encoded via a select number of "specialist receptors" that are narrowly tuned to detect their specific ligand, or whether predator cues are encoded in a combinatorial manner via broadly tuned olfactory receptors. Together, these experiments will provide insight into how information about an entire class of ethologically relevant odorants is organized in the brain. By revealing general principles by which the mammalian brain detects and processes behaviorally meaningful odorants, the proposed experiments will provide a conceptual framework to ultimately understand how the neural circuits mediating odor-evoked behaviors are modified by experience and disease.

Public Health Relevance

Many neurological disorders such as anxiety and post-traumatic stress disorder arise from the inability of the brain to properly couple sensory stimuli with appropriate behaviors. Our experiments will reveal general principles by which the brain encodes and organizes sensory information for behaviorally important odorants, thereby providing a platform to ultimately understand what goes wrong in pathological states and to develop effective treatments for such disorders.

National Institute of Health (NIH)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZDC1)
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Sklare, Dan
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Harvard Medical School
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United States
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