The symptoms of Parkinson’s Disease (PD) are primarily the result of the death of dopamine-producing neurons in the midbrain. In the striatum, the main input nucleus of the basal ganglia, dopamine interacts with major glutamate input from the cerebral cortex and thalamus. Abnormal neuronal oscillations and synchrony are observed in the basal ganglia of both PD patients and in animal models of PD and are correlated with changes in the distribution of subtypes of glutamate N-methyl-D-aspartate (NDMA) receptors. The most complete model to date of the medium spiny projection neuron (MSN) of the striatum has implicated NDMA receptors, in particular the slow decay of the currents they mediate, as key regulators of synchronization of this input nucleus to the basal ganglia with its cortical and thalamic afferents. Molecules interacting with the NMDA receptor have shown promise as potential drug therapies in animal models of PD, but the anatomical substrate for this action is unknown. Given the dominant role of the thalamus and cortex in orchestrating oscillations in relation to brain states, it is important to understand NMDA receptor subunit composition at the thalamostriatal and corticostriatal synapses, as these may constrain interactions between the basal ganglia, thalamus and cortex in the normal and diseased brain. We have recently developed a novel rat brain slice preparation to examine glutamate receptor subtypes utilized in the thalamostriatal and corticostriatal pathways in a single MSN. The studies to date demonstrate that the thalamostriatal and corticostriatal synapses utilize different NMDA/non-NMDA ratios and different NMDA receptor subunits providing a physiological substrate that could mediate afferent pathway-specific modulation in the striatum. Experiments using 6-OHDA-lesioned rats show that the relative NMDA receptor content at these two synapses changes in response to dopamine lesion. These changes in NMDA receptor content could contribute to some of the symptoms associated with PD and are potential sites of action for the observed effects of NMDA receptor antagonists in animal models of PD.