Distribution and ultrastructural features of the serotonin innervation in rat and squirrel monkey subthalamic nucleus

The main purpose of this light and electron microscopic immunocytochemical study was to characterize and compare the serotonin (5‐HT) innervation of the subthalamic nucleus (STN) in rats and squirrel monkeys (Saimiri sciureus) following labeling with an antibody against the 5‐HT transporter (SERT). Unbiased counts of SERT+ axon varicosities revealed an average density of 5‐HT innervation higher in monkeys (1.52 × 10⁶ varicosities/mm³) than rats (1.17 × 10⁶), particularly in the anterior half of the nucleus (1.70 × 10⁶). As measured by electron microscopy, SERT+ axon varicosity profiles in the STN of both species were smaller than unlabeled profiles. The number of SERT+ profiles displaying a synaptic junction indicated that, in both rat and monkey STN, approximately half of 5‐HT axon varicosities were asynaptic. In monkeys, all synaptic junctions made by SERT+ varicosities were asymmetrical, as opposed to only 77% in rats. Despite the higher density of 5‐HT innervation in the anterior half of monkey STN, the ultrastructural features of its SERT+ varicosities, including synaptic incidence, did not significantly differ from those in its posterior half. These findings suggest that, throughout the rat and monkey STN, 5‐HT afferents may exert their influence via both synaptic delivery and diffusion of 5‐HT, and that an ambient level of 5‐HT maintained in STN by these two modes of transmission might also modulate neuronal activity and influence motor behavior. A better understanding of the factors governing the complex interplay between these signaling processes would greatly improve our knowledge of the physiopathology of the STN.