PREFERENTIAL GROWTH OF NEONATAL RAT DORSAL-ROOT GANGLION-CELLS ON HOMOTYPIC PERIPHERAL-NERVE SUBSTRATES IN-VITRO

Developing sensory neurons interact with molecular signals in the loca l environment to generate stereotypic nerve pathways. Regenerating neu rons seem to lose the ability to reinnervate their original sites in t he targets, resulting in abnormal sensory input and consequent clinica l pathophysiology. The specificity of reinnervation of peripheral targ ets by regenerating axons is thus crucial for normal recovery of funct ion. In this study, we have examined evidence for selectivity of inter actions between primary afferent neurons from identified levels of the spinal cord and different peripheral nerve environments by culturing these neurons on sections of nerves to muscle and viscera. We have com pared the growth of a population of sensory afferents normally innerva ting somatic targets (dorsal root ganglion cells from L4 and L5) with populations containing many afferents innervating visceral targets (L6 and S1 dorsal root ganglia and nodose ganglion). These neurons, from newly born rats, were cultured on unfixed cryostat sections of normal and prelesioned gastrocnemius nerve, pelvic spinal nerve and vagus ner ve from adult rats, Normal muscle nerve was seen to support the regene ration of a significantly greater proportion of somatic neurons, with longer neurites, than the visceral nerves. Similarly, much higher prop ortions of the 'visceral' population of afferent neurons were seen to extend neurites on the normal visceral nerve substrates, with longer n eurites, than on the muscle nerve substrate. The selectivity displayed by the sensory neurons for their normal nerve substrates was abolishe d when they were cultured on prelesioned nerve substrates subjected to Wallerian degeneration, which was apparent from the equivalent and in creased proportions of growing neurons having comparable neurite lengt hs, on all the nerve substrates. We conclude that sensory neurons reco gnize and respond to substrate-specific and substrate-bound molecules present in normal adult peripheral nerves, and that these differences are lost in prelesioned nerves following Wallerian degeneration.