The striatum is the main input structure of the basal ganglia, which is necessary for proper motor function and habit formation. The medium spiny projection neurons (MSPNs), which comprise ~95% of striatal neurons, undergo changes in synaptic strength during the learning of a motor task 
. This synaptic plasticity is thought to be the cellular basis of motor learning and habit formation, and it is disrupted in animal models of Parkinson's Disease 
and Huntington's Disease 
One of the critical mechanisms for inducing synaptic plasticity in neurons is calcium elevation in the spine. The sources of calcium are quite diverse, and depend on brain region and direction of plasticity. In particular, LTD often requires release of calcium from internal stores 
or voltage dependent calcium channels 
. In contrast, the source of spine calcium that contributes to long-term potentiation (LTP) is the NMDA receptor (NMDAR) in the hippocampus 
, cortex 
, and striatum 
Because NMDARs permit calcium influx in response to the coincidence of pre-synaptic glutamate release and post-synaptic depolarization, they are well situated to modulate spike timing dependent plasticity (STDP). In STDP protocols, an action potential (AP) is caused by depolarizing the soma of a neuron and is paired in time with a pre-synaptic stimulation. However, NMDARs differ in several properties that may be critical for timing-dependent synaptic plasticity. They contain various combinations of GluN1,2, and 3 subunits which can change their maximal conductance, current decay time, and sensitivity to magnesium block 
. While the GluN1 splice variant has some control over the kinetic properties of the NMDAR, the four GluN2 subunits (A, B, C, and D) strongly control them when the GluN1 splice variant is kept the same 
. The GluN2 subunit can thereby alter the calcium influx through the NMDAR. Because the specific differences between GluN2 subunits are the ones that would affect the NMDARs dependence on AP timing, and because calcium through the NMDAR plays an essential role in striatal timing-dependent long term potentiation (tLTP) 
we hypothesized that changes in GluN2 subunit would modulate STDP in the striatum.
The MSPNs of the striatum contain both GluN2A and GluN2B subunits in abundance 
, and it has been suggested that GluN2D subunits may be present in low concentrations 
. In animal models of Parkinson's disease, the NMDAR subunit composition is altered in the striatum 
and subunit-specific NMDAR antagonists have been shown to alleviate Parkinson's like symptoms 
. However, the intracellular consequences of such altered NMDAR subunit composition has not yet been made clear. In this study, we investigate the effects of altering NMDAR subunit composition on tLTP in the striatum.
Using a multi-compartmental model of a MSPN, we examine NMDAR-mediated calcium influx through receptors containing different GluN2 subunits and under different STDP conditions. We find that calcium elevation depends on which GluN2 subunit the NMDAR contains, the relative timing of the AP, the duration of somatic depolarization, and the number of consecutive APs. More significantly, model predictions about the effect of GluN2 subunit on the shape of the STDP curve are confirmed experimentally.