Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

The hypothalamus is the brain region responsible for maintaining homeostatic balance of the body in terms of core body temperature, blood pressure and fluid salt concentrations. Hypothalamic dysfunction can lead to cardiovascular and kidney disease, sleep and psychological disturbances, diabetes, and body temperature dysregulation. Two hypothalamic regions, the supraoptic nucleus (SON) and the organum vasculosum lamina terminalis (OVLT), work together to detect the body's fluid salt composition (osmolality) to maintain arterial blood pressure and water balance. Specifically, neurons in the OVLT detect osmolality, and relay this information to the SON to cause hormone (vasopressin; VP) release into the bloodstream to sustain steady body fluid osmolality and vascular tone. Interestingly, changes in core body temperature can also cause VP release, but how this occurs is unknown. We have published previous reports that show this process involves heat-sensing proteins (TRPV channels) present in the SON and OVLT. As follow-up, we propose to investigate how SON and OVLT neurons respond to temperature and osmolality changes through TRPV channels using a variety of experimental techniques available in our laboratory. In particular, we will determine which types of TRPV channels (out of four known subtypes) are present in heat- and osmolality-responsive SON and OVLT neurons, and we will investigate how these neurons communicate with other hypothalamic neurons to cause VP release. Little is presently known about how homeostatic balance of the body is achieved within the hypothalamus; therefore these experiments will provide necessary information that can be used toward understanding and treating cardiovascular disease. TRP channels are involved in several genetic diseases, cardiovascular and kidney diseases, and some cancers; thus, gaining a better understanding of how these channels function in the brain may lead to novel treatment targets for a broad range of illnesses.