Expression, Function and Plasticity of NMDA Receptor Subunits on Magnocellular Neuroendocrine Cells

University Of California-Riverside, Riverside CA

Investigators

Abstract

One major goal of this proposal is to further characterize the subunits that makeup the N-methyl-D-aspartate (NMDA) receptor complex on neuroendocrine cells in the brain. These neurons control body water (osmoregulation) by producing hormones such as vasopressin and oxytocin. These neuroendocrine cells are located in the supraoptic (SON) and paraventricular nucleus (PVN) of the hypothalamus. The composition of NMDAR2 subunits, in particular, is thought to underlie differences in the function of NMDA receptors. The proposed studies will examine the molecular expression of NMDAR2 subunits in neuroendocrine cells using state-of-the-art molecular techniques as well as pharmacological and antisense technology. In addition, the experiments have been designed to examine the functional contribution of NMDAR2 subunits to NMDA receptors on neuroendocrine cells. An examination of the structure of NMDA receptors in the SON and PVN, which may display all five of the NMDA receptor subunits, will provide information on one of the most potentially unique NMDA receptor subtypes in the brain. One longterm objective of this research is to yield an understanding of the role of NMDA receptor subunits in osmoregulation. To begin to address this issue we will examine the effect of osmotic activation of SON and PVN neuroendocrine cells on their expression of selected NMDA receptor subunits. Our previous research findings indicate that these cells display dramatic changes in NMDAR1 and NMDAR2B subunit levels during dehydration. The proposed experiments will investigate the cellular components showing subunit changes, regional specificity and reversibility upon rehydration. Finally, we will explore the possibility that NMDAR2B-containing receptors on neuroendocrine cells can be biochemically altered and that physiological signals such as dehydration can provide the signal for regulation. Basic principles revealed by the proposed studies will provide essential information about the properties of NMDA receptor subtypes in the neuroendocrine nuclei of the brain. Effects of osmotic signals on the expression of NMDA receptor subunits may provide clues about the role of NMDA receptors in fluid homeostasis and other neuroendocrine functions. In addition, our findings will contribute new insights into regulatory mechanisms important in central nervous system function.