Organization of the nigrothalamocortical system in the rhesus monkey

Abstract

The nigrothalamocortical connections and their topography were analyzed by autoradiography and double or triple retrograde labeling with the fluorescent dyes Fast Blue, Diamidino Yellow, and Propidium Iodide. Injections of tritiated leucine into different parts of the substantia nigra (SN) revealed that the medial SN projects to the medial magnocellular subdivisions of the ventral anterior (VAmc) and mediodorsal (MDmc) nuclei of the thalamus while the lateral SN projects to the more lateral and more posterior part of the VAmc, and the paralaminar, parvicellular, and densocellular subdivisions of the mediodorsal nucleus (MDmf, MDpc, and MDdc). With the exception of the MDmf, terminal areas observed in the mediodorsal nucleus were in the form of scattered clusters of grains. Analysis of the thalamus in cases with fluorescent dye injections into the lateral orbital gyrus (Walker's area 11), principal sulcus (area 46), anterior bank of the arcuate gyrus (areas 8 and 45), supplementary motor area (area 6), and motor cortex (area 4) revealed topographic organization of the nigrothalamocortical projection system. The parts of the VAmc and MDmc which receive afferents from the medial part of the SN in turn project to the most anterior regions of the frontal lobe including principal sulcus and orbital cortex. The lateral posterior VAmc, MDmf, MDpc, and MDdc, all of which receive afferents from the lateral part of the SN; project to more posterior regions of the frontal lobe including, in addition to the principal sulcus, the frontal eye field and also areas of the premotor cortex. These findings indicate that the SN has preferential targets in the thalamus and cerebral cortex which are segregated from those of the globus pallidus and cerebellum. Whereas the motor cortex is the primary target of cerebellar output (Asanuma et al., '83b), and the premotor cortex is the target of pallidal output (Schell and Strick, '84), the SN output appears to be directed more anteriorally--to the prefrontal cortex.

The thalamic connections of motor, premotor, and prefrontal areas of cortex in a prosimian primate (Otolemur garnetti)

“…Fourth, the other two regions of the presumptive motor thalamus, VM and VA, have only minor connections with areas of motor cortex, and their main functions may not be motor. These nuclei have connections with prefrontal cortex, FEF and pre-SMA in monkeys (Kunzle and Akert, 1977;Goldman-Rakic and Porrino, 1985;Ilinsky et al, 1985;Morel et al, 2005), and our injections in prefrontal cortex of galagos labeled these nuclei. In monkeys, projections from the substantia nigra to VA and VM (Macchi and Jones, 1997) implicate these nuclei in motor functions, although direct projections from VAmc and VM to motor areas of cortex in macaques are sparse.…”

Distribution of Dopamine D3 Receptor Expressing Neurons in the Human Forebrain Comparison with D2 Receptor Expressing Neurons

“…These regions provide input to the anterior nuclei of the thalamus (Groenewegen et al 1990). The AV of the thalamus, which exhibits the highest expression of D 3 receptors within the thalamus, receives a nigrothalamic GABAergic innervation from the SNr (Ilinsky et al 1985), a region of relatively higher expression of D 3 and D 2 receptors. This provides multiple sites at which drugs such as antipsychotics might act to regulate activity in the "limbic" loop via interaction with the D 3 receptor.…”

“…The AV appears to represent a major site of interaction of the D 2 and D 3 receptors, because it possesses both types of binding sites in comparable concentrations as well as neurons expressing one or both mRNA species. The AV receives a nigrothalamic innervation from the SNr, a region of relatively higher expression of D 3 than D 2 receptors, via GABAergic nigrothalamic pathway (Ilinsky et al 1985;Kultas-Ilinsky and Ilinsky 1990), which may be originating from non-dopaminergic D 3 mRNA positive neurons frequently observed in SNr. The AV also receives massive projections from the MM through the mtt, the former enriched with D 3 mRNA and the latter with binding sites.…”

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

“…Indeed, anatomical tracings have shown that STN neurons project to SNr, which in turn target the DLPFC through the nigral-receiving area of thalamus. 147 Nonetheless, it seems plausible that GPi HFS could have antidromically activated STN projections collateralizing in both the GPi and the SNr and thus indirectly affected the DLPFC.…”