Previous studies have shown that NMDA receptors mediate much of the normal synaptic transmission in magnocellular neuroendocrine cells of the supraoptic nucleus of the hypothalamus (SON). Dr. Curras's laboratory has recently shown that osmotic activation of the hypothalamo-neurohypophysial axis produces upregulation of the glycine-binding subunit of the NMDA receptor, NMDAR1. These changes in NMDAR1 expression are specific to the SON and paraventricular nucleus of the hypothalamus (PVN) suggesting that NMDA receptors are also involved in neuroendocrine function.
Recent molecular cloning studies have identified five NMDA receptor subunits: NMDAR1 and NMDAR2A-D. In the adult SON all but the NMDAR2A gene are expressed. Preliminary studies in the investigator's laboratory have detected robust expression of NMDAR2B and NMDAR2D subunit and light expression of NMDAR2A and NMDAR2C subunits. One of the goals of the proposed research is to examine the subunit composition of functional NMDA receptors present on neurons of the SON. Western blot analysis and patch-clamp electrophysiology combined with pharmacological strategies will be used to examine the NMDA receptor structure and function indicative of subunit composition. Since functional NMDA receptors are believed to be composed of NMDAR1 and at least one NMDAR2 subunit, it is proposed to examine expression changes induced by osmotic activation of the glutamate-binding subunit, NMDAR2B.
