The cortex sends excitatory glutamatergic input to the striatum, which modulates the globus pallidus interna (GPi) and the substantia nigra reticulata (SNr). The GPi and the SNr in turn send inhibitory GABAergic progections to the thalamus, which provides glutamatergic innervation back to the cortex.
The striatum modulates the GPi and the SNr via two pathways: one direct and one indirect. These pathways begin with GABA-ergic medium spiny neurons (MSNs). MSNs are the main neuron that makes up the human striatum. D1 dopamine receptor modulated MSNs send GABAergic inhibitory projections directly to the globus pallidus interna (GPi). D2 dopamine receptor modulated MSNs send GABAergic inhibitory projections to the GPe. The GPe sends GABAergic inhibitory inputs to the subthalamic nucleus (STN), which provides excitatory dopaminergic input to the GPe and the SNr. D1 receptor signaling increases dendritic excitability of MSNs, while D2 receptor signaling decreases dendritic excitability of striatopallidal MSNs.