Body temperature has profound influences on all aspects of animal biology. Mammals have the ability to control body temperature by adjusting their physiology (e.g. non-shivering thermogenesis, perspiration) and by behavioral measures (e.g. huddling, locating areas of more favorable temperatures or thermotaxis). This process is thought to involve an internal set point and complex feedback loops that rely on thermoreceptor neurons in the skin and in the hypothalamus. Our understanding of the connections between such thermoreceptor neurons and motor centers is incomplete at best. Even less is known about the mechanisms of sensorimotor integration responsible for behavioral thermoregulation and its modification during short-term and long-term acclimation. In the nematode C. elegans, by contrast, a single pair of thermoreceptor neurons is linked to changes in behavioral responses to thermal gradients (thermotaxis). Their connections with interneurons and, ultimately, with motor neurons are known. Thus, in C. elegans, it is possible to understand how thermoreceptor neuron signaling affects behavior at a level of detail that is not possible in mammals. In this exploratory proposal, we seek to expand understanding of the link between temperature sensation and behavior by investigating the mechanism by which mutations can disrupt this link and by developing new tools for altering neuronal function. We focus on a mutant isolated in our laboratory that exhibits an intriguing defect in sensorimotor integration. We seek to extend this work by screening for genes responsible for the development and/or function of neurons that link thermosensation to motor output and to develop new tools for analyzing behavioral responses to neuron activation. The general strategy is to combine classical genetics with quantitative behavioral analysis and in vivo whole-cell patch-clamp recording in order to elucidate the relationship between temperature sensation and its behavioral consequences. The long-term objective of the proposed is to establish C. elegans as a new model for the study of behavioral thermoregulation and sensorimotor integration. The relevance of this project to human health lies in its potential to uncover universal motifs in sensorimotor integration and to provide insight into thermal dysregulation. ? ? All animals, including humans, have the ability to regulate their body temperature by moving to favorable areas in the environment. This ability relies on nerve cells that sense temperature and communicate with the nervous system to produce the needed movements. This complex process is only poorly understood. To improve understanding, we will study a simple roundworm that has only 302 neurons. Two of these neurons sense temperature and appear to aid a form of thermoregulation. What is learned from this study will clarify basic mechanisms of temperature sensation as well as learning and could improve understanding of thermoregulation and its dysfunction in disease and in response to recreational drugs such as ecstasy. ? ? ?
Showing the most recent 10 out of 13 publications
