The most well-known form of synaptic plasticity, NMDAR-dependent, was first discovered in 1973 in the hippocampi of anesthetized rats (Bliss and Lomo, 1973) and has since been extensively characterized from electrophysiological recordings of in vitro hippocampal slice preparations. Long-term potentiation (LTP) is defined as an increase in the post-synaptic response resulting from a cascade of events which is initiated by an influx of Ca2+ ions through voltage-gated pre-synaptic ion channels. The NMDAR-dependent form of LTP requires postsynaptic depolarization during NMDAR activation, which will allow for an influx of Ca2+ ions through the channel within the dendritic spine. This increase of Ca2+ will commence a series of intracellular signaling, activating a number of protein kinases and consequently lead to the insertion of AMPA receptors into the plasma membrane. In contrast, long term depression (LTD) is attributed to a weak activation of NMDARs, minimal Ca2+ influx, and a reduction in post-synaptic AMPA surface receptor density via dynamin- and clathrin-dependent endocytosis (Malenka and Bear, 2004). Much of the NMDAR-dependent plasticity has focused on mechanisms responsible for the initial increase in synaptic strength, however
