The aims of this proposal will determine mechanisms by which the internal state of stress alters neural activity. Even the most logical and brilliant can suddenly turn incoherent when riddled with anxiety. Strikingly, twenty percent of adult Americans suffer from debilitating stress. The inability to faithfully find stress-responsive neurons throughout the brain has stalled the field's ability to discover the mechanisms of precisely how stress impacts neurons to alter behavior. What is needed is a robust experimental platform for us and others to reliably use as a model to investigate how the internal state of stress alters neural function and behavior. Our preliminary data indicates that the state of stress silences subsets of neural activity in easily identified, well defined subsets of mouse olfactory sensory neurons. Stress silencing of neural activity has a black and white effect on behavior; if an individual cannot sense an odor cue they do not appropriately respond to the environment. In itself, this is surprising because it has been thought that the olfactory system is just a passive sensory collector vacuuming up environmental cues and passing that information to the brain. Instead, our preliminary data reveals that olfactory sensory neurons are capable of responding to an individual's current stress state, and that this response inhibits the sensation of olfactory stimulus. In order to determine how sensory neuronal activity is inhibited by the state of stress in both the main and accessory olfactory systems we will 1) elucidate the stress signals from the adrenal glands that are detected by olfactory sensory neurons, 2) identify the receptors on the olfactory sensory neurons that detect stress signals, and 3) determine the molecular mechanisms that enable stress to silence sensory neurons. Completion of these aims will open up new horizons to study the scope of function of olfaction. More broadly, this work will provide a molecular solution for us and others to use as a template for mechanistic study of the action of stress hormones throughout the more complicated brain. We anticipate that these results will precipitate new understanding of how sensory systems, the brain, and the body collectively generate behavior.
The proposed research is relevant to public health because it will provide a new, simple, experimental platform to study how changes in internal state, such as stress, alter neural activity. Completion will guide us and others to effectively study the action of stress hormones throughout the brain.
|Keller, Jason A; Chen, Jingyi; Simpson, Sierra et al. (2018) Voluntary urination control by brainstem neurons that relax the urethral sphincter. Nat Neurosci 21:1229-1238|