The Skaggs Institute
for Chemical Biology

Scientific Report 2007

Molecular Biology of Olfaction

L. Stowers, P. Chamero, K. Flanagan, D. Logan, T. Martin, F. Papes, C. Ramos

Behavior is largely governed by sensory perception in humans. However, our understanding of the complete list of events that link the detection of sensory stimuli to the consequential generation of specific behaviors is limited. The sense of olfaction involves of 2 types of neurons: (1) those that are activated by odorants and mediate an evocative perception that varies with an individual's experience, thereby leading to a variety of associated behaviors, and (2) those that are activated by pheromones that are detected subconsciously, without associated perception, and thereby lead to the regulation of stereotyped innate social behaviors such as mating and maternal behaviors.

Pheromone stimuli elicit a variety of specific innate behaviors in rodents, providing a unique opportunity to study the detection-perception-behavior pathway at the molecular and cellular levels. We expect that elucidating the stimulating ligands and responsive neurons will enable us to activate, study, and identify the mechanisms that underlie neural information coding of defined behaviors.

We have been isolating the chemical ligands, pheromones, that specifically govern social behaviors such as aggression and mating. However, these ligands are detected in rodents by neurons and mechanisms that are active in all terrestrial vertebrates but are not functional in humans. To expand our investigation of innate neural circuits, we have begun to additionally elucidate the ligands and responsive sensory mechanisms that promote maternal-infant behavior. Isolation of these pheromones enables us to specifically activate, and thereby identify, the population of sensory neurons dedicated to promoting maternal-infant behavior. Our results suggest that this fundamental social behavior is governed by a unique subset of sensory neurons that may have functional orthologous counterparts in humans. To further investigate these neurons, we are isolating the unique molecules, such as ligand receptors, signal transduction elements, and ion channels, that uniquely define this subset of neurons. Identifying these molecules will allow us to investigate the kinetics of their response and to genetically manipulate their properties to validate their role in promoting behavior. We expect that our studies will provide the tools to expand our understanding of the logic of neuronal coding of innate behaviors in mice and, additionally, investigate the molecular mechanisms that underlie human social behavior.

Publications

Chamero, P., Marton, T.F., Logan, D.W., Flanagan, K., Cruz, J.R., Saghatelian, A., Cravatt, B.F., Stowers, L. Identification of protein pheromones that promote aggressive behaviour. Nature 450:899, 2007.