Sympathetic noradrenergic sprouting in response to central cholinergic denervation; a histochemical study of neuronal sprouting in the rat hippocampal formation.

An unusual example of neuronal sprouting occurs in the rat brain. Several weeks after fimbrial transection or septal lesions, peripheral sympathetic fibers appear in the dentate and hippocampal gyri. We compared the distribution of normal cholinergic septohippocampal fibers and nerve terminals with the distribution of noradrenergic sympathetic (sympathohippocampal) fibers after septal lesions using anterograde transport of horseradish peroxidase and fluorescence histochemistry. In addition, we destroyed other afferents to the hippocampal formation and examined the effect of subtotal septal lesions on acetylcholinesterase staining and the distribution of sympathohippocampal fibers. The combined results of these experiments suggest that peripheral noradrenergic fibers sprout specifically in response to destruction of central cholinergic fibers after septal lesions. This appears to be the first model of neuronal sprouting in the central nervous system where one identified transmitter system (noradrenergic) sprouts only in response to, and perhaps to replace, another specific transmitter system (cholinergic).