The NMDA receptor is involved in a wide range of physiological and pathophysiological events. Recent studies have indicated that the NMDA receptor is phosphorylated on tyrosine residues and that this phosphorylation may modulate NMDAR currents and even overall signalling in response to NMDA receptor activation. So far only acute c changes in receptor current after activation of tyrosine signalling pathways have been studied. The present proposal will extend these studies to the longer durations of hours to days in order. It may then be possible to examine changes in the number of active receptors in response to activation of tyrosine kinase signalling pathways. The medical relevance of tyrosine phosphorylation of NMDA receptors includes possible roles in ischemia, 6-OH-daopamine lesioning of nigrostriatal neurons, and chronic neuroleptic treatment.
