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Date of Award

12-1980

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

Supervisor

Professor Jack Diamond

Abstract

One approach to the study of how nerves can establish appropriate connections, and of possible "plasticity" intrinsic to the connections themselves, is to partially denervate a target tissue and examine the reestablishment of functional connections by nerves. Cells or tissues whose normal nerve supply has been lesioned can become reinnervated by two means: the sprouting of new collaterals from nearby intact nerves, or the regeneration of the damaged fibres. Both mechanisms have been reported as involved in the recovery of function after nerve lesions in mammals.

In the course of experiments on the reinnervation of skin in rabbits, however, evidence was obtained suggesting that intact low-threshold mechanosensory nerves in adult mammals may not sprout into denervated skin. The investigations described in this thesis were undertaken to examine this possibility further, and in particular to use the rat to study the ability of such nerves to establish functional connections in denervated skin.

Direct electrophysiological recording from cutaneous nerve bundles was used to detect impulses generated by tactile stimulation of the skin. The area of skin supplied by a nerve (its low-threshold mechanosensory receptive field) and in particular the number of touch domes (specific sensory structures in the skin) innervated by that nerve were determined after various manipulations; both the area of the field and the population of touch domes were used as measures of the distribution in the skin of functional endings. Intact low-threshold mechnosensory nerves in the rat were found to sprout into adjacent denervated skin only during a remarkably brief "critical period" that begins at about 15 days of age and ends at about 20; such sprouting could neither be evoked nor did it continue after this age. Moreover, during the critical period, the intact low-thershold mechanosensory nerves often failed to sprout into denervated skin except that available within the same ("parent") dermatome. These intact nerves therefore are under constraints both in time and space, which operate to limit the extent of functional sprouting and also the location of such newly established endings. Regenerating nerves however were found to be subject to neither of these constraints, and even in the adult they would freely grow across dermatomal borders to establish functional endings in denervated skin. Of special significance, when the regenerating nerves arrived at skin that during the critical period had been reinnervated by sprouts of intact nerves, the regenerating fibres replaced funtionally the earlier sprouted endings; those endings within the usual territory of the intact nerve that had sprouted were not displaced however.

It was concluded that intact and regenerating nerves are differentially regulated, intact nerves, but not regenerating ones, are subject to temporal and spatial constraints in their ability to establish functional endings in denervated skin. The endings which are established in response to denervation of skin during the critical period however incompletely suppress some quality of the target which allows regenerating nerves to recognize it, and to engage successfully in competition for its innervation.

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