The Skaggs Institute
for Chemical Biology
Molecular Biology of Olfaction
L. Stowers, P. Chamero, K. Flanagan, D. Logan, T. Martin, F. Papes, C. Ramos
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.
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.
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.