Are there three subdivisions in the primate subthalamic nucleus?

Abstract

The prevailing academic opinion holds that the subthalamic nucleus (STN) consists of three parts, each anatomically distinct and selectively associated with cognitive, emotional, or motor functioning. We independently tested this assumption by summarizing the results from 33 studies on STN subdivisions in human and nonhuman primates. The studies were conducted from 1925 to 2010 and feature three different techniques: electrical lesions, anterograde and retrograde tracers, and classical cytoarchitectonics. Our results reveal scant evidence in support of a tripartite STN. Instead, our results show that the variability across studies is surprisingly large, both in the number of subdivisions and in their anatomical localization. We conclude that the number of subdivisions in the STN remains uncertain, and that academic consensus in support of a tripartite STN is presently unwarranted.

Keywords: primate; subdivisions; subthalamic nucleus.

Figure 1

Connection profile and subdivisions of the STN show highly variable results. (Top of figure) Color-coded lesion, anterograde, and retrograde tracer injection sites including cortical, subcortical, and brainstem regions. In the middle, the anatomical orientation of the STN template is displayed. Three schematic slices from caudal to rostral are shown. Anatomical abbreviations: BA, Brodmann Area; CMAd, Cingulate Motor Area dorsal; CMAr, Cingulate Motor Area rostral; CMAv, Cingulate Motor Area ventral; GPe, Globus Pallidus external segment; GPi, Globus Pallidus internal segment; HVIIB, Gracial Lobule; M1, Primary Motor cortex, PMd, Pre-Motor dorsal; PMv, Pre-Motor ventral; PPN, Pedunculopontine Nucleus; Pre-SMA, Pre-Supplementary Motor Area; S1, Primary Sensory cortex; SMA, Supplementary Motor Area; SN, Substantia Nigra compacta; SNr, Substantia Nigra reticularis; VA, Ventral Anterior Nucleus; VL, Ventral Lateral Nucleus. (A–F) Six studies arguing for zero subdivisions. The author and publication year is shown in the left upper corner. (G–U) Fifteen studies arguing for two subdivisions. The author and publication year is shown in the left upper corner. (V–Y) Four studies arguing for three subdivisions. The author and publication year is shown in the left upper corner. (Z–AA) Two studies arguing for four subdivisions. The author and publication year is shown in the left upper corner. Black arrows denote the direction of connection. The red arrow denotes the location of a lesion. Localization of subdivisions within the STN are color coded according to the injection or lesion site.

Figure 2

Reported number of subdivisions sorted by the year of publication, method and species. (A) Histogram including studies that argue for subdivisions in the STN published during the past 45 years, summarized in time-windows of 15 years. (B) Histogram including studies that argue for subdivisions in the STN separated for (a) the type of tracer used, and (b) the species under investigation. Color indicates the number of subdivisions reported. Blue bars indicate no subdivisions, red bars indicate two subdivisions, green bars indicate three subdivisions and purple bars indicate four subdivisions.

Figure 3

The variable location of subdivisions within the STN based on six individual studies using classical cytoarchitectonic features. Six human and nonhuman studies are shown that argue for either zero or two subdivisions. For each study, three schematic slices from caudal to rostral are displayed. Shaded areas refer to different subdivisions in the STN.