REGENERATION OF CENTRAL CHOLINERGIC NEURONS IN ADULT RAT-BRAIN

The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted in 2 different brain sites: the caudal diencephalon and hippocampus and the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 wk after lesion, newly formed, probably sprouting fibers could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibers into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibers into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides and then stained for AChe. During the first 2-4 wk after transplantation the sprouting central fibers grew out over large areas of the iris. The new fibers branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibers mimicked closely that of the normal autonomic cholinergic innervation of the iris. In 1 series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibers in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibers in the transplant. This indicates that, as in the normal iris, the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus coeruleus neurons) regenerate together along the denervated Schwann cell sheaths. From a comparison between the central reinnervation process and the process of reinnervation of the iris by peripheral cholinergic axons after transplantation to the anterior eye chamber, the regenerative capacity of central cholinergic neurons (above all the septo-hippocampal system) is apparently not much inferior to that of their peripheral counterparts when given similar growth conditions. Central cholinergic neurons seem partly able to replace the peripheral ones in the reinnervation of a denervated peripheral target.