Objetivo
Excitatory synaptic transmission in the central nervous system is mediated by glutamate receptors (GluR). In the hippocampus, the NMDA subtype of GluR provides a mechanism for Ca2+ entry into the neurons during synaptic activity, thereby triggering various forms of synaptic plasticity. However, the overstimulation of NMDA receptors leads to an excessive accumulation of intracellular Ca2+, resulting in neurotoxicity. The NMDA receptor has regulatory binding sites for glycine, poliamines, protons, Zn, Mg, and its activity can be modulated by a large number of drugs. Despite massive efforts devoted over the last few years to understand the mechanisms of NMDA receptor function, many important questions remain unclear.
This study will focus on the different modulatory binding sites of the NMDA receptor complex. Using electrophysiological, biochemical, pharmacological, and fluorometric approaches a study will be made of how binding of non-competitive agonists and antagonists influence the physiological function of NMDA receptors. First, the action of the drugs on freshly isolated rat hippocampal pyramidal neurons will be examined. The knowledge obtained will then be applied further to study the modulation of glutamatergic synaptic transmission in hippocampal slices. The study will enhance understanding of NMDA receptor function in the mammalian brain and will provide insight into the mechanisms which underlie learning and memory formation.
Convocatoria de propuestas
Data not availableRégimen de financiación
Data not availableCoordinador
66421 Homburg-Saar
Alemania