Grant: Project Grant

Few would probably dispute that one of the most important functions of the brain is learning and memory. If you open up any modern neuroscience textbook, you will learn that NMDA receptors are critical for memory formation in the brain. It is therefore perhaps not so surprising that these receptors have been implicated in devastating neurological diseases such as Alzheimer's, epilepsy, and schizophrenia. In recent years, however, its become clear that our understanding of NMDA receptors is incomplete. For example, they are sometimes located on transmitting instead of receiving side of neuronal connections, where they cannot function according to the standard textbook view on how learning in the brain operates. Furthermore, they sometimes signal metabotropically, i.e. in the absence of depolarising neuronal activation, which completely changes how neuroscientists think about their function. This proposal will explore tow unorthodox modes of NMDA receptor signalling: on the transmitting side, and metabotropically. This is a virtual blank on the map, and must be understood to treat major neurological pathologies such as Alzheimer's and epilepsy.