Grant: Operating Grant

Changes in blood osmolality (a measure of the body's salt and water content) can lead to severe neurological problems including (in proportion to the anomaly): headache, mental confusion, seizures, coma and death. Changes in osmolality (e.g. during heat stroke, dehydration or hyponatremia), common in the elderly and in hospitalized patients, are caused by asymmetric gains or losses of salt (mainly sodium) and water. The regulation of blood osmolality is achieved in part through changes in antidiuretic hormone (ADH) release from the posterior pituitary gland. The brain regulates this release in response to fluctuations in body temperature and changes in plasma osmolality. Increasing our understanding the molecular and cellular mechanisms through which this control is achieved should eventually reveal new and more effective therapeutic approaches to the treatment of fluid balance disorders. Dr. Bourque's project aims to identify the neurons responsible for the detection of changes in body temperature and osmolality within the hypothalamus using physiological, anatomical and molecular biological approaches. The experiments will define how these neurons and local glial cells interact with each other to control the electrical activity of ADH neurons. Our experiments specifically propose to define the role of a new family of proteins called TRPV channels, that may serve as molecular integrators of temperature and osmolality.