ULTRASTRUCTURAL ANALYSIS OF TRYPTOPHAN-HYDROXYLASE IMMUNOREACTIVE NERVE-TERMINALS IN THE RAT CEREBRAL-CORTEX AND HIPPOCAMPUS - THEIR ASSOCIATIONS WITH LOCAL BLOOD-VESSELS

Physiological evidence has indicated that serotonin (5-hydroxytryptami ne) could be a regulator of cerebral blood flow in various regions of the brain. In the present study, tryptophan hydroxylase immunocytochem istry was used to characterize, both at the light and electron microsc opic levels, serotonergic nerve terminals and primarily their relation ships with intraparenchymal microarterioles and capillaries in the rat frontoparietal cortex, entorhinal cortex and hippocampus. Irrespectiv e of the brain area, serotonergic varicosities were primarily apposed to either dendrites or nerve terminals, were on average 0.37 mu m(2) i n surface area (0.69 mu m calculated diameter) and 12-22% of them enga ged in synaptic junctions, mostly with dendritic elements. Perivascula r terminals (defined as immunolabelled varicosities located within a 3 mu m perimeter around the vessel basal lamina) in the frontoparietal cortex represented 8-11% of all immunoreactive terminals counted, as d etermined by light and electron microscopy, respectively. In the entor hinal cortex and hippocampus, the proportion of perivascular terminals was only determined at the ultrastructural level and corresponded to 10% and 4%, respectively. In the frontoparietal cortex, serotonergic v aricosities were located significantly closer (n = 250, 0.98 +/- 0.05 mu m; P < 0.001) to the blood vessels than those of the entorhinal cor tex (n = 116, 1.41 +/- 0.08 mu m) or hippocampus (n = 105, 1.31 +/- 0. 08 mu m). Of all perivascular serotonergic terminals in the frontopari etal cortex, 26% were in the immediate vicinity (0-0.25 mu m) of the v essel wall, with 2.8% directly abutting on the basement membrane, whil e 11.6% were separated from it only by a thin astrocytic leaflet. This situation contrasts with that observed in the entorhinal cortex and h ippocampus, where no immunoreactive varicosity was ever seen directly contacting the vessel basal lamina and with only 10-13% of the termina ls being within 0.25 mu m from the vessels. The surface area of periva scular serotonergic terminals was comparable in all regions studied an d corresponded to 0.22 mu m(2); these virtually never engaged in synap tic contacts with adjacent neuronal structures. Our results indicate t hat tryptophan hydroxylase-immunolabelled terminals are identical to p reviously characterized serotonin-containing varicosities. Furthermore , the present data show intimate associations between serotonergic ter minals and microvessels in the three regions examined. However, periva scular terminals in the frontoparietal cortex were more frequent and/o r located much closer to local microvessels than those in the other re gions, and might be more directly involved in neurogenic control of lo cal cerebral blood flow.