The SNr and GPi outputs are both tonically active inhibitory nuclei and are thus constantly inhibiting the thalamus (and thus motor cortex). However, transient activity in (inhibitory) direct pathway medium spiny neurons ultimately disinhibits thalamus projections to the motor cortex and enables movement. The indirect pathway also receives excitatory input from various brain regions. Indirect pathway medium spiny neurons project to the external segment of the globus pallidus (GPe). Like the GPi, the GPe is a tonically active inhibitory nucleus. The GPe projects to the excitatory subthalamic nucleus (STN), which in turn projects to the GPi and SNr. When the indirect pathway is not activated, activity in the STN is suppressed by the GPe, which translates to decreased SNr/GPi activity downstream and thus increased thalamic and motor cortex neuron activity. When indirect pathway neurons fire, GPe neurons are inhibited, which disinhibits the STN. The STN then excites SNr/GPi neurons, suppressing thalamus/motor cortex activity. Classic models of striatal function have posited that activation of the direct pathway leads to movement, whereas activation of the indirect pathway leads to the termination of movement. This model is supported by experiments demonstrating that optogenetically stimulating direct pathway medium spiny neurons increases locomotion, whereas stimulating indirect pathway medium spiny neurons inhibits locomotion. The balance of direct/indirect activity in movement is supported by evidence from neurodegenerative disorders, including Parkinson's disease (PD), which is characterized by loss of dopamine neurons projecting to the striatum, hypoactivity in direct pathway and hyperactivity in indirect pathway neurons, along with motor dysfunction. This results in loss of normal action selection, as loss of dopamine drives activity in the indirect pathway, globally inhibiting all motor paradigms. This may explain impaired action initiation, slowed actions (bradykinesia), and impaired voluntary motor initiation in Parkinson's patients. On the other hand, Huntington's disease, which is characterized by preferential degradation of indirect pathway medium spiny neurons, results in unwanted movements (chorea) that may result from impaired movement inhibition and predominant direct pathway activity. An alternative related hypothesis is that the striatum controls action initiation and selection via a ’center-surround’ architecture, where activation of a subset of direct pathway neurons initiates movements while closely related motor patterns represented by surrounding neurons are inhibited by lateral inhibition via indirect pathway neruons.