RAPID SEROTONERGIC FIBER SPROUTING IN RESPONSE TO IBOTENIC ACID LESION IN THE STRIATUM AND HIPPOCAMPUS

Serotonergic (5-HT) sprouting occurs after damage of neighboring 5-HT or non-5-HT fibers. The sprouting signals appear to originate from the target tissue where neural trophic factors are secreted. In order to determine the cellular source of the trophic signal we currently repor t that removal of local neurons with a neurotoxin, ibotenic acid (IB), triggered a vigorous sprouting of 5-HT fibers in the striatum as earl y as 3 days after the lesion, which lasted throughout the entire lengt h (21 days) of our study. The 5-HT fiber density in the injection site increased 10-fold in the striatum compared to the contralateral side, and the density of 5-HT varicosities increased 4-fold of normal. The 5-HT level in the striatum correspondingly increased on the lesion sid e. Three clear morphological concentric zones were formed by the lesio n: acellular, aneuronal and outer zones. These zones represent the cha racteristic reorganization of astrocytes and neurons following an inje ction of IB. Devoid of any cells, the small acellular zone in the cent er of the injection site contained few 5-HT fibers. Devoid of neurons, the aneuronal zone contained reactive astrocytes and an abnormally hi gh density of 5-HT fibers with increased staining of S-100. Containing neurons and astrocytes, the outer zone had a normal 5-HT fiber densit y. The induced 5-HT sprouting in the aneuronal zone strongly suggests that local neurons could provide a trophic factor, but that astrocytes would be the most plausible candidate. This is not an isolated case, IB injections in the hippocampus also induce a similar phenomenon.