Hyperinnervation of arrested granule cells produced by the transplantation of monoamine-containing neurons into the fourth ventricle of rat

An attempt to learn whether chemically specific neurons affect the sequence of cerebellar development was made by transplanting ectopic tissues rich in monoamines adjacent to the early developing cerebellum of neonatal rat. Three types of brainstem grafts were used: (1) ventral midline raphe region, (2) inferior olivary region, (3) locus coeruleus region. When transplanted into the fourth ventricle of host animals, neurons from the transplant sprout axons into the host cerebellar parenchyma producing changes in cerebellar cytoarchitecture. The changes produced by the three types of brain grafts were investigated with conventional light and electron microscopy. Autoradiography with tritiated serotonin (3H-5HT) and norepinephrine (3H-NE) and immunocytochemistry using antibodies raised against serotonin allowed identification of the chemical specificity of the process. The three fundamental changes caused by the transplants were folial malformation, arrest of migration of external granule cells, and disruption of the Purkinje cell monolayer. By intraventricular infusion of 3H-5HT and immunocytochemistry with antibodies raised against serotonin, an extraordinarily rich serotonin innervation was detected within or around the foci of arrested granule cells after transplantation with raphe-rich tissue. In addition to an increase in the number of parallel fibers that accumulate 3H-5HT, numerous glomerulus-like structures were observed within the foci. After transplantation with locus coeruleus fragments, intraventricular infusion of 3H-NE demonstrated some increase of labeled fibers inside the foci of arrested granule cells, but the extent of the increase of NE fibers was less marked than the increase in 5-HT fibers. Conventional electron microscopic study revealed numerous synaptic formations within the arrested granule cell foci. Terminals containing large granular vesicles were seen, which resemble serotonin nerve terminals previously described (Chan-Palay, 1975, 1977).