PI: Summy-Long, J. IBN-9724091 Large cells in the brain that produce the hormones vasopressin (VP) and oxytocin (OT) comprise the magnocellular neuroendocrine system. These cells also make nitric oxide (NO), a gas that regulates the function of neurons and their interconnections and cellular structure. These structural changes (termed plasticity) are known to occur on oxytocinergic neurons late in pregnancy and are maintained throughout lactation. Current research indicates that NO, as well as OT, released within the brain during nursing, may be necessary to maintain these plastic changes in the oxytocinergic neuron. In the proposed research it is postulated that more magnocellular cells synthesize or produce NO during lactation to meet the increasing demand for NO to influence plasticity. Current methods in neuroscience (immunohistochemistry and in situ hybridization) will be used to localize and count the number of cells throughout the magnocellular system that express different forms of NO synthase, the enzyme needed to produce NO. Specifically, we will determine if an increased expression of NO synthase occurs in magnocellular neurons during lactation. Findings from these proposed studies will clarify a role for NO in regulating plasticity of the magnocellular system during lactation. Aside from the recognized contribution to our understanding of the neuroendocrinology of lactation, these studies have the potential to increase our knowledge regarding the action of NO on the nervous system with implications for the neurobiology of learning and memory and the treatment of neurodegenerative diseases.