Organization of efferent projections of the subthalamic nucleus in the squirrel monkey as revealed by retrograde labeling methods

Abstract

The cellular origin and degree of collateralization of the subthalamostriatal, subthamonigral and subthalamopallidal projections in the squirrel monkey ( Saimiri sciureus) were studied using lectin-conjugated horseradish peroxidase (WGA-HRP), Nuclear yellow (NY) and Fast blue (FB) as retrograde tracers. In a first experimental group, WGA-HRP was injected in the left putamen and the right caudate nucleus. Followingl these injections numerous retrogradely labeled neurons occured in the dorsolateral two-thirds of the subthalamic nucleus on the putamen-injected side, whereas a smaller numebr of positive cells were found in the ventromedial third of the same nucleus on the caudate-injected side. In a second experimental group NY was injected in the putamen whereas FB was delivered in the substantia nigra on the same side of the brain. After putaminonigral injections subthalamic cells containing the tracer injected in the putamen (about 75–80% of all retrogradely labeled neurons) occured in the dorsolateral two-thirds of the nucleus, whereas those containing the tracer injected in the substantia nigra (about 20–25% of all positive subthalamic cells) were confined to the ventromedial third of the structure. Approximately 5–10% of all subthalamic positive neurons were double-labeled following putaminonigral injections. In a third experimental group, NY was injected in the caudate nucleus and FB in the substantia nigra on the same side. After such injections cells retrogradely labeled with NY or FB were present in about equal number and appeared closely intermingled in the ventromedial third of the subthalamic nucleus. Less than 10% of all positive subthalamic neurons were double-labeled following caudatonigral injections. In a fourth experimental group, NY was delivered in the globus pallidus and FB in the substantia nigra on the same side. In these animal cells containing the tracer delivered in the pallidum were about 4 times more numerous than those labeled with the tracer injected in the substantia nigra, and approximately 10–20% of all positive subthalamic neurons were double-labeled following pallidonigral injections. Most of these double-labeled cells occured in the zone where the two populations of single-labeled cells overlapped. Finally, in a last experimental group, NY was injected in the pedunculopontine nucleus on one side and in the substantia nigra on the other. Following these injections cells containing the tracer delivered in the pedunculopontine nucleus were found to be 5–6 times less numerous than those labeled after substantia nigra injections. These findings suggest that in regard to its efferent projections, the primate subthalamic nucleus is organized according to a complex pattern consisting of: (1) a large (80%) dorsolateral ‘sensorimotor’ zone where most neurons project to the lenticular nucleus and terminate in the globus pallidus and/or the putamen. (2) a small (20%) ventromedial ‘associative’ zone neurons give to either ascending projections to caudate nucleus or descending projections to the substantia nigra, and (3) a smaller (10%) overlapping zone whose neurons send axon collaterals to both the lenticular nucleus and the substantia nigra.