The subthalamic nucleus is one of multiple innervation sites for long-range corticofugal axons: a single-axon tracing study in the rat.

The frontal cortex provides strong excitatory inputs to the subthalamic nucleus (STN), and these cortico-STN inputs play critical roles in the control of basal ganglia activity. It has been assumed from anatomical and physiological studies that STN is innervated mainly by collaterals of thick and fast conducting pyramidal tract axons originating from the frontal cortex deep layer V neurons, implying that STN directly receives efferent copies of motor commands. To more closely examine this assumption, we performed biotinylated dextran amine anterograde tracing studies in rats to examine the cortical layer of origin, the sizes of parent axons, and whether or not the cortical axons emit any other collaterals to brain areas other than STN. This study revealed that the cortico-STN projection is formed mostly by collaterals of a small fraction of small-to-medium-sized long-range corticofugal axons, which also emit collaterals that innervate multiple other brain sites including the striatum, associative thalamic nuclei, superior colliculus, zona incerta, pontine nucleus, multiple other brainstem areas, and the spinal cord. The results imply that some layer V neurons are involved in associative control of movement through multiple brain innervation sites and that the cortico-STN projection is one part of this multiple corticofugal system.