The molecular mechanisms underlying experience-dependent modification of synaptic strength have been under intense investigation because of their fundamental importance in brain functions including learning and memory. Within the visual system, two naturally occurring synaptic changes, potentiation and depression, can be detected in response to light deprivation and this 'plasticity' requires N-methyl-D-aspartate receptors (NMDARs). NMDARs are a subtype of glutamate receptor and the ratio of synaptic NMDAR subunits, NR2A to NR2B (NR2A/2B ratio) changes in response to visual experience and deprivation. Recent evidence suggests that NR2A/2B ratio changes may also underlie the direction of synaptic modification termed metaplasticity. Using visual cortex slice and in vivo recordings, we propose to determine the causal role of NR2A/NR2B ratio changes in plasticity events by increasing or reducing NR2 subunit protein levels in a mouse model for experience-dependent plasticity. Results from the proposed work should provide mechanistic insight and therefore therapeutic value for disorders where learning and memory are impaired such as autism, and Alzheimer's. ? ?
