The role of NMDA receptor signaling in regulating the stability of excitatory synapses
12 / 2006 - 12 / 2008
Nederlandse Organisatie voor Wetenschappelijk Onderzoek - NWO
In the developing brain, neurons connect with other neurons to form circuits. The assembly of functional neuronal circuitry requires the proper formation and stabilization of synaptic contacts between neurons. Although much has been learned in recent years about the initial formation of synapses, it is largely unknown how synapses are stabilized once they are formed. The NMDA glutamate receptor is thought to play a crucial role in this process. This research project aims to unravel the role of NMDA receptor signaling in regulating the stabilization of synapses and the assembly of synaptic contacts into functional neuronal circuits. We will investigate the hypothesis that different NMDA receptor subunits play a critical role in regulating the formation and elimination of synapses. To this end we will use cultured neuronal networks, live imaging of synapses, and mice in which the NR2A and NR2B NMDA receptor genes are conditionally deleted at different developmental stages. Understanding how NMDA receptor signaling regulates the assembly of a functional neuronal network is essential for a deeper insight in how the brain is wired during development and for the eventual treatment of NMDA receptor-related neurological disorders such as schizophrenia, epilepsy and neurodegeneration.