Subthalamic nucleus of the monkey: connections and immunocytochemical features of afferents

Retrograde and anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was studied in 7 squirrel monkeys with discrete injections of the subthalamic nucleus (STN). Injections labeled: (1) the lateral two-thirds of the nucleus (63% and 47%), (2) ventrolateral parts caudally (20%), (3) dorsomedial parts caudally (18%), (4) rostromedial parts (21%), (5) the medial third (38%) and (6) the lateral pole of the nucleus (9%). Afferents to the lateral two-thirds of the STN originated from two parallel cellular arrays in dorsal parts of the middle third of the lateral pallidal segment (LPS) and a single array in the rostral third of the LPS. Medial regions of the STN received input from cells in the rostral LPS. Small numbers of cells were retrogradely labeled in the centromedian-parafascicular (CM-PF) and the pedunculopontine (PPN) nuclei. No cells were labeled in the frontal cortex, the striatum, the substantia innominata (SI), the substantia nigra (SN) or the dorsal nucleus of the raphe. Virtually all pallidal neurons, including identified pallidosubthalamic neurons, were immunoreactive (IR) for gamma-aminobutyric acid (GABA). Pallidosubthalamic neurons were most numerous in regions of the LPS with the lowest density of leucine enkephalin-IR fibers. Substance P-IR fibers, found mainly in the medial pallidal segment, bore no relationship to pallidal afferents to the STN. Choline acetyltransferase-IR cells in the SI and the PPN were not retrogradely labeled with WGA-HRP granules. Anterograde transport in fibers and terminal fields surrounded retrogradely labeled cells in the LPS, suggesting a reciprocal relationship. The caudal third of the LPS and ventral region of the middle third of this nucleus, appeared to project few fibers to, or to receive few fibers from, the STN. A small number of STN efferents entered the medial border of the putamen, but no terminal fields were identified. STN projections to the pars reticulata of the SN appeared to represent about 10% of the projection to the LPS. No STN efferents were identified in the frontal cortex, the SI or the PPN. The hypothesis that STN afferents from the frontal cortex and CM-PF may represent collaterals of projections to other loci is discussed.