Interconnections and organization of pallidal and subthalamic nucleus neurons in the monkey

Attempts were made to determine the topographic organization of subthalamopallidal and pallidosubthalamic projections in order to evaluate interconnections between the subthalamic nucleus (STN) and the globus pallidus (GP). In a series of monkeys retrograde and anterograde axoplasmic transport technics were used to explore these interconnections. Small volumes of horseradish peroxidase (HRP) were injected selectively into: (1) the medial pallidal segment (MPS), (2) the rostral division of the lateral pallidal segment (LPS, rostral to the medial medullary lamina of the GP), and (3) the central division of the LPS (lateral to the medial medullary lamina of GP). Retrograde transport of the enzyme to cells in the STN indicated that: (1) cells in the medial and caudal third of the nucleus project predominantly to the MPS, (2) cells in medial portions of the middle third of the nucleus project predominantly to the rostral division of the LPS, and (3) cells in central portions of the rostral two-thirds of the nucleus project to the central division of the LPS, with the largest contribution derived from rostral regions of the nucleus. An inverse dorsoventral topographical relationship appears to exist between cells in the STN and axonal terminations in the LPS, in that cells in dorsal regions of the STN project to ventral regions of the LPS, while cells in ventral regions of the STN project to dorsal regions of the LPS. No similar relationship could be established between the STN and the MPS because of its smaller size. Cells in the lateral third of the STN do not project terminals to the MPS or the rostral or central divisions of the LPS. It is suggested that cells in the lateral third of the STN project to the caudal division (caudal to the medial medullary lamina of the GP) of the LPS. A small number of cells in the pedunculopontine nucleus project to the MPS. Pallidosubthalamic projections were determined from autoradiographs based upon injections of [3H] amino acids into the MPS, the LPS, and both segments of the GP. Selective labeling of cells in the MPS resulted in no transport of isotope to any part of the STN. Labeling of cells in the rostral division of the LPS resulted in transport of isotope to: (1) the medial two-thirds of the rostral part of the STN and (2) the central region of the middle third of the nucleus. Cells in the central division of the LPS projected fibers to the lateral third of the STN throughout most of its rostrocaudal extent. Even though the STN is a relatively small nucleus, it appears organized into afferent and efferent portions with respect to the GP. Subthalamopallidal fibers originate mainly from the medial two-thirds of the STN and are topographically organized; cells in specific and separate locations within the STN project to wellcircumsumscribed terminations within either the MPS or the LPS. These data do not support the thesis that major axonal collaterals of STN neurons supply both pallidal segments, although this possibility cannot be excluded. Subthalamic neurons projecting to the MPS arise from cells in medial and caudal parts of the nucleus that do not receive projections from any part of the GP or from the cerebral cortex. Pallidosubthalamic projections derived from the rostral and central divisions of the LPS terminate in distinctive loci within the STN. Comparisonsof these regions of termination with those that give rise to subthalamopallidal projections suggest that direct reciprocal connections between the STNand the LPS must be partial. If functional reciprocal connections exist between STN and the two major segments of the GP, these are not on a point forpoint basis and local interneurons must be involved.