Specificity of initial synaptic contacts made on guinea-pig superior cervical ganglion cells during regeneration of the cervical sympathetic trunk

Abstract

1. Largely appropriate synaptic connexions are formed with neurones in the superior cervical ganglion at long intervals after interruption of the preganglionic nerve. In the present study we have assessed the accuracy of connexions during the early stages of re-innervation by observing end-organ responses to ventral root stimulation in vivo, and by recording intracellularly from ganglion cells during ventral root stimulation in isolated preparations. 2. Appropriate, but weak, end-organ responses were elicited by stimulation of the first and fourth thoracic ventral roots (T1 and T4) 15--30 days after freezing the cervical sympathetic trunk. 3. Intracellular recordings from ganglion cells during stimulation of the ventral roots C8--T7 in vitro showed that synaptic contacts are first re-established 8--11 days after freezing the preganglionic nerve. The proportion of re-innervated cells, and the strength of innervation of individual neurones, increased rapidly for up to about 3 months after nerve injury, but showed little change thereafter. Innervation remained weaker than normal even after 6 months. 4. Patterns of segmental innervation recorded intracellularly during the early stages of regeneration were similar to, but more restricted than normal. Even 13--19 days after interruption of the preganglionic nerve, neurones re-innervated by more than one spinal cord segment tended to be innervated by a contiguous subset of the spinal segments which contribute innervation to the ganglion. The incidence of neurones receiving innervation from a discontinuous segmental subset was about the same at early and late stages or re-innervation. 5. Throughout the course of nerve regeneration, re-innervated neurones tended to receive dominant synaptic input from axons arising at a particular spinal level, as do normal cells, with adjacent segments contributing a synaptic influence that diminished as a function of distance from the dominant segment. 6. The results of these experiments argue against the initial formation of imprecise connexions with subsequent retention of appropriate contacts and a loss of inappropriate ones. Rather our findings suggest that the re-innervation of ganglion cells proceeds by a gradual accumulation of synaptic connexions which are, from the outset, appropriate.