Grant: Project Grant

Maintenance of body temperature near 37C is regulated by the brain and is essential for life in mammals including humans. The importance of thermoregulation is demonstrated by the negative impact of a fever on our well-being. A fever is caused by altering the set point of the neural circuit that mediates thermoregulation (like adjusting a thermostat to a higher value). Once established, a fever helps accelerate recovery from infection and dissipates quickly when the threat has been eliminated. However, there are many pathological circumstances in which dysregulated thermoregulation can alter body temperature in a life-threatening manner. Conversely, there are also clinical conditions where artificially changing body temperature can be beneficial. For example, as an adjunct treatment for some forms of cancer and heart attacks. Our ability to control body temperature in a clinical setting is crude and extremely limited in the field. Gaining new information about the molecular and cellular mechanisms that mediate thermoregulation could provide new approaches for precise regulation of body temperature using simpler approaches, including drugs. The process of thermoregulation involves "command" neurons wired to brain areas that induce behavioral (e.g. seeking warm or cool environments) and physiological responses (e.g. sweating or shivering) to mediate cooling or heating as required. Moreover, a key requirement for correct thermoregulation is the existence of temperature sensing neurons that encode on-going body temperature. Remarkably, we still do not know what molecule is responsible for physiological temperature detection and how neurons that express this molecule communicate with command neurons that mediate thermoregulation. This project will investigate the hypothesis that a specific subset of neurons expressing the thermosensitive ion channel dN-Trpv1 are essential for thermoregulation in mice.