The neocortex and basal ganglia operate together through cortico-basal ganglia-thalamocortical circuits to execute movements and goal directed behaviors. The neocortex communicates with the basal ganglia through parallel sets of glutamatergic corticostriatal projections that synapse on striatal medium-sized spiny neurons. These excitatory signals are modified at the medium spiny neuron by dopamine, released from midbrain projections and by acetylcholine released from striatal interneurons. Combined, these neurotransmitters provoke state changes in medium spiny neurons and determine whether signalling proceeds through direct or indirect striatal pathways that ultimately determine basal ganglia output. Neurodevelopmental and neurodegenerative disorders that affect motor function are associated with abnormal activation of the corticostriatal pathway. The abnormal release of dopamine, acetylcholine and ...