SYMPATHETIC SPROUTING - TIME-COURSE OF CHANGES OF NORADRENERGIC, CHOLINERGIC, AND SEROTONERGIC MARKERS IN THE DENERVATED RAT HIPPOCAMPUS

As a first step for experiments investigating the presynaptic characte ristics of sympathetic fibers grown into the denervated hippocampus, w e studied the time course of changes of neurochemical markers in the r at hippocampus, subsequent to aspiration lesions of the fimbria-fornix and the overlying callosal and cortical structures. At various postsu rgical delays (1, 2, 8, 24, and 40 weeks), the activity of choline ace tyltransferase, the high-affinity synaptosomal uptake of choline and n oradrenaline, and the concentrations of noradrenaline, serotonin, and 5-hydroxyindoleacetic acid were measured in a dorsal, an intermediate, and a ventral part of the hippocampus. Levels of all markers were sig nificantly reduced shortly (1-2 weeks) after the lesions. However, whe reas the cholinergic (choline uptake and choline acetyltransferase act ivity) and the serotonergic (concentrations of serotonin and 5-hydroxy indoleacetic acid) markers remained significantly reduced for up to 40 weeks, both noradrenergic markers recovered to near-normal (noradrena line uptake) or even supranormal (noradrenaline concentration) levels, although with clear-cut differences in the time course and the region al characteristics. The noradrenaline content reached control levels a lready 8 weeks after lesion surgery and was about two to three times h igher 40 weeks later, with the most dramatic effects in the ventral hi ppocampus. In contrast, high-affinity noradrenaline uptake reached con trol values only 24 weeks after lesion and exceeded them only in the v entral hippocampus 40 weeks after surgery. It is concluded (a) that hi ppocampal noradrenaline concentration is a more sensitive marker for s ympathetic sprouting than high-affinity noradrenaline uptake and (b) t hat functional in vitro studies on hippocampal sympathetic ingrowth ap pear to fit optimal conditions in the ventral hippocampus at a delay o f at least 40 weeks after surgery.