| Abstract No.: | A-D1151 |
| Country: | Canada |
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| Title: | SEROTONIN INNERVATION OF THE SUBTHALAMIC NUCLEUS IN MONKEY AND HUMAN. |
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| Authors/Affiliations: | 2 Marie-Josée Wallman*; 1 Martin Parent; 1 Laurent Descarries; 2 André Parent;
1 Université de Montréal, QC, Canada; 2 Université Laval, Québec, QC, Canada
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| Content: | Immunocytochemistry with an antibody raised against the plasma membrane serotonin transporter (5-HTT) was used to study the serotonin innervation of the subthalamic nucleus (STN) in squirrel monkeys (Saimiri sciureus) and in human individuals deceased without neurological or psychiatric disease. This innervation arises chiefly from the dorsal raphe nucleus, with a minor contribution from the median raphe nucleus. The 5 HTT+ axons detach themselves laterally from a thick bundle that ascends along the lateral hypothalamic area. In human, these axons run along both dorsal and ventral surfaces of the STN, enter the nucleus mainly from its medial portion, and arborize in a remarkably uniform manner throughout its entire extent. In monkey, the pattern of distribution is less homogeneous. Unbiased counts of 5-HTT+ axon varicosities obtained from 8 different STN sectors with the optical fractionator (Stereo Investigator, MicroBrightField) demonstrate a antero-posterior decreasing gradient, with an average of 1.7 and 1.3 million varicosities/mm3 in the anterior and posterior sectors, respectively. The 5 HTT+ axon varicosities in the STN of the monkey were also examined in the electron microscope. These varicosity profiles were generally smaller (average diameter: 0.46µm2) than those of unlabeled varicosity profiles selected at random in the neighbouring neuropil (0.81µm2). In single thin sections, 10% only displayed a synaptic junction, compared to > 40% of unlabeled profiles. As extrapolated stereologically to the whole volume of varicosities, this suggests a synaptic incidence of 42% for the 5-HTT+ varicosities. All junctions formed by the synaptic 5-HTT+ varicosities were asymmetrical, and almost equally shared between dendritic branches and spines. Despite the higher density of innervation in the anterior half of STN, there were no significant differences between the ultrastructural features of 5-HTT+ varicosities, including synaptic incidence, between anterior and posterior halves. Altogether, these morphological findings indicate that the dorsal raphe nucleus may exert its influence on primate STN through both synaptic delivery and diffusion of serotonin. The STN occupies a crucial position in the functional organization of the basal ganglia. Its 5-HT input could thus play an important role in the normal functioning of the basal ganglia, as well as in the pathogenesis of motor disorders that result from a malfunction of this complex set of subcortical forebrain structures.
Grant/Other Support: CIHR Grant MOP-5781
Grant/Other Support: CIHR Grant MOP-3544
Grant/Other Support: H.H. Jasper Fellowship (GRSNC)
Grant/Other Support: FRSQ Fellowship
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