Serotoninergic axon terminals in the rat dorsal accessory olive: Normal ultrastructure and light microscopic demonstration of regeneration after 5,6-dihydroxytryptamine lesioning

SummaryThe serotoninergic innervation of the lateral portion of the dorsal accessory nucleus of inferior olive (DAO) was studied using high resolution radioautography after intraventricular or intracisternal administration of tritiated serotonin ([3H]5-HT). In normal adult rats, the axonal varicosities labelled with [3H]5-HT were of round-elongate shape and averaged 0.6–1.0μm in diameter. They contained microcanaliculi (15–25 nm in diameter), tubular-vesicular elements (25–40 nm) and large granular vesicules (80 nm), as well as mitochondria and smooth endoplasmic reticulum. Among 750 thin-sectional profiles of labelled varicosities, only 5% showed a differentiated area of membrane specialization which suggests that not more than one out of 7–8 varicosities was engaged in a synaptic junction. This serotoninergic innervation was therefore categorized as non-junctional. There were nevertheless certain structural features suggestive of polarity even in the ‘non-synaptic’ serotoninergic varicosities of the lateral DAO: many labelled profiles exhibited aggregation of their microcanalicular and tubular-vesicular organelles against a part of their membrane apposed to a dendritic process, while the remainder of their periphery was usually surrounded by glia. These observations reinforced the supposition that non-junctional as well as junctional serotoninergic varicosities might release transmitter.Counts in light microscope radioautographs indicated that the lateral DAO of normal rat receives about 4.5 million serotoninergic varicosities per mm3. Denervation by intraventricular 5,6-dihydroxytryptamine (5,6-DHT) was severe, leaving only 0.45 million per mm3 after five days. It was followed by rapid regrowth, however, since an approximately normal number of serotoninergic varicosities was again measurable two months after 5,6-DHT. The growth process continued further, and six months after 5,6-DHT, the lateral DAO exhibited a ‘hyperinnervation’ of 12.6 million varicosities per mm3. This re-establishment of a serotoninergic innervation was in line with our hypothesis concerning the factors influencing the course of neuroplasticity. According to this hypothesis, innervations of the non-junctional variety may regenerate after neurotoxic lesioning, whereas those making numerous synaptic connections are replaced by local sprouting of intact afferents.