Long-term potentiation (LTP) and long-term depression (LTD) are lasting, activity-dependent changes in synaptic strength that have been proposed to underlie learning and memory. These forms of plasticity are dependent on NMDA receptor activation, and recent studies have suggested that the subunit composition of these NMDA receptors (specifically whether the receptor complex contains the NR2A versus the NR2B subunit) plays an important role in whether their activation leads to LTP or LTD. However, these studies are primarily pharmacological, have provided conflicting results, and their conclusions remain somewhat controversial.
The first aim of this proposal is to use pharmacological antagonists to determine whether the roles of the NR2A and NR2B in long-term plasticity change over development.
The second aim i s to investigate the roles of these subunits as molecular scaffolds in addition to their roles as receptor-channels. This will be done by evaluating the impact on LTP and LTD of decreasing NR2A and NR2B expression using RNAi.
The third aim i s to increase NR2A expression in the visual cortex of light-deprived rats to study the role of NR2A in experience-dependent plasticity. ? ?
| Foster, Kelly A; McLaughlin, Nathan; Edbauer, Dieter et al. (2010) Distinct roles of NR2A and NR2B cytoplasmic tails in long-term potentiation. J Neurosci 30:2676-85 |
