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The Stowers Lab
The sense of olfaction drives behavior. The odor environment can entice us to eat, evacuate a room, or profoundly relax. How the sense of smell generates behavior is largely a mystery. My lab has advanced our understanding by identifying and purifying specialized odors that promote innate behavior and studying the circuits and mechanisms of perception.
1. Specific pheromone chemosignals that generate stereotypic behavior
Synthetic, emotion-generating pheromones provide an experimentally simple means to activate, identify and study currently unknown subsets of relevant neurons. We aimed to isolate several ligands that trigger negative valence behavior such as rage and fear, as well as several ligands that trigger positive valence behavior such as infant bonding and male/female attraction. To isolate pheromones, we start with robust behavior and evaluate fractions of native secretions to identify the bioactive molecule. Therefore, we not only discovered the elusive ligands, but also immediately knew their function. We have repeated this approach and have deliberately discovered 11 ligands that stimulate aggression, attraction, and defensive behavior (eliciting both positive and negative motivation).
2) Sensory neurons that detect pheromones and other specialized chemosignals
We are investigating the coding logic of olfactory sensation. The vomeronasal organ (VNO) detects specialized odorants that trigger social and survival behaviors. We have previously found that female sensation of male odors is not passively fixed, but instead is modulated to be sensitized or silenced to align her behavior with her ovulatory cycle (Cell;161:1334). This is an unusual feature of a sensory system, which we expect should provide a fixed and accurate representation of the external world. We are now revisiting the molecular biology of VNO primary sensory transduction and find it does not follow expected rules of vision, taste, or main olfaction. These other sensory systems are arranged so that many sensory receptors impinge on a single sensory transduction cascade, translating sensation into a common neural language for the brain to interpret. In contrast, the mouse VNO appears to utilize a variety of different primary sensory modules, spatially restricted in the VNO epithelium and restricted to expression with a limited variety of VNO receptors. We propose that the variety of primary signal transduction modules provides a framework for distinct signals from different subsets of receptors which may be further modulated to personalize signaling to the needs of the receiver.
3) Neural and molecular mechanisms in the brain that result in stereotypic behavior
We are leveraging olfaction to understand how the brain and the body generate social behavior. Courtship behavior is an innate model for many types of brain computations including sensory detection, learning and memory, and internal state modulation. Despite the robustness of the behavior, we have little understanding of the underlying neural circuits and mechanisms. The Stowers’ lab is leveraging the ability of specialized olfactory cues, pheromones, to specifically activate and therefore identify and study courtship circuits in the mouse. We are interested in identifying general circuit principles (specific brain nodes and information flow) that are common to all individuals, in order to additionally study how experience, gender, age, and internal state modulate and personalize behavior. We are solving two parallel sensory to motor courtship circuits, that promote social vocal calling and scent marking, to study information processing of behavior as a complete unit instead of restricting focus to a single brain region. We expect comparing and contrasting the coding logic of two courtship motor behaviors will begin to shed light on general principles of how the brain senses context, weighs experience and responds to internal state to ultimately decide appropriate action.
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