An Integrated Approach to Understanding Temperature Sensation and Its Behavioral Consequences

Stanford University, Stanford CA

Investigators

Abstract

Body temperature has profound influences on all aspects of animal biology. All animals, including humans, have the ability to regulate their body temperature by moving to favorable areas in the environment. This behavioral thermoregulation is thought to involve thermosensory neurons in the skin, an internal set point and complex feedback. A major challenge in understanding behavioral thermoregulation is to identify animals amenable to mechanistic analysis. With only 302 nerve cells (neurons), the roundworm C. elegans is an almost perfect organism for such studies. It is the only animal in which the shape of every neuron and its connections to other neurons is known (the wiring diagram). A sub-circuit of 11 bilaterallysymmetric neurons mediate initial responses to temperature. All of these neurons can be identified in living animals, including a pair of neurons that sense cooling and warming (the AFD cells) and are critical for thermotaxis. In C. elegans, but not in mammals, it is possible to directly measure how these neurons respond to temperature. The proposed research leverages these advantages of C. elegans and takes an integrated approach, analyzing temperature sensation at the molecular and cellular level. Experiments are proposed to deconstruct the molecular networks that make temperature sensation possible and to discover genes responsible for the development or function of neurons that link sensation to behavior. Because the wiring diagram is known, future experiments can investigate the neural circuit linking temperature sensation by AFD to motor output. In C. elegans, the AFD neurons are critical for successful thermotaxis. Other nematodes, which are parasites of agriculturally important plants and animals, are thought to use thermotaxis as part of a host-finding strategy. Some of these parasitic nematodes are known to have neurons similar to AFD, suggesting that the proposed research could have broader implications. In particular, what is learned about the molecular networks responsible for temperature could provide entry points for new research into methods for controlling nematode species that threaten agriculture. The intellectual merit of this work lies in the establishment of a new animal model for mechanistic analysis of temperature sensation and its behavioral consequences. It has the potential to offer insight into universal molecular, cellular and network-level mechanisms by which sensory information provides essential, real-time feedback for movement. The work derives broad impact from its multidisciplinary approach, combining the experimental and conceptual tools of genetics, cell physiology, and behavioral studies. Since its inception, high school students and undergraduates have contributed to the work, including women and minority participants in the Stanford Summer Research Program. Research opportunities for undergraduates will continue to be an integral part of the proposed work. Additionally, the PI encourages lab members to participate in community outreach activities and provides release time for this important work.