This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Excessive activation of the N-Methyl-D-Aspartate (NMDA) receptor mediates neurotoxicity and neurodegeneration under many neurological conditions. The underlying mechanisms remain unknown. The aim of this project is to test the hypothesis that PSD-95 plays an important role in the survival of striatal medium spiny neurons (MSNs) and their vulnerability to NMDA receptor excitotoxicity and elucidate the underlying mechanisms.