Selective reinnervation of intercostal muscles transplanted from different segmental levels to a common site

Abstract

We transplanted external intercostal muscles from one of several thoracic (T) levels to the neck of adult rats. The cervical sympathetic trunk, which innervates the superior cervical ganglion, was cut, and its proximal end was apposed to the muscle. Preganglionic axons in the trunk reinnervated muscle fibers in the transplants. We determined the segmental origin of synaptic inputs to transplanted muscles by recording intracellularly from muscle fibers while stimulating individual ventral roots which supply axons to the trunk. In one series of experiments, T2 or T8 muscles were transplanted from the thorax to the neck of the same rat. While T2 and T8 muscles were reinnervated to a similar extent, they differed in the segmental origin of the innervation they received: T2 muscles received more inputs from rostral segments (T1 and T2) than did T8 muscles, and T8 muscles received more inputs from caudal segments (T4 to T6) than did T2 muscles. This difference between reinnervation of T2 and T8 muscles was detected both 2 to 4 weeks and 10 to 14 weeks after surgery. In a separate series, using rats of an inbred strain, T3, T4, or T5 muscles were transplanted from one rat to a separate host. Again, the average segmental origin of inputs to transplants from different levels differed systematically: it was most rostral to T3 muscles, intermediate to T4 muscles, and most caudal to T5 muscles. Finally, T3 and T5 muscles were soaked in a myotoxin, Marcaine, before reimplantation. This treatment kills muscle fibers but not myoblastic satellite cells; therefore, muscle fibers were replaced by regeneration. Marcaine-treated T3 and T5 muscles were successfully reinnervated but did not differ significantly in the segmental origin of their inputs. Our results show that adult mammalian muscles can be selectively reinnervated, and they raise the possibility that the selectivity is based on some positional quality that matches axons and muscles from corresponding segments. However, while differences among muscles survive denervation and transplantation, their expression or accessibility may change during regeneration.

Evidence for compartmental identity in the development of the rat lateral gastrocnemius muscle

“…This interpretation is at least philosophically similar to that of the segmental identity of intercostal muscles, forelimb muscles, and the diaphragm proposed by Sanes and his co-workers (e.g., Wigston and Sanes, 1985;Wigston, 1986;Laskowski and Sanes, 1987;DeSantis et al, 1992). Both during development and during reinnervation, muscle fibers in different regions within these muscles receive selective innervation from motoneurons in different segmental regions of the spinal cord.…”

Guidance of regenerating motor axons in larval and juvenile bullfrogs

“…Regenerating preganglionic axons in the mammalian autonomic nervous system exhibit segmental selectivity during reinnervation of superior cervical ganglion neurons (Langley, 1897;Nja and Purves, 1977). Furthermore, when preganglionic axons are forced to grow into transplanted intercostal muscles, they innervate those inappropriate targets in a manner that is segmentally specific (Wigston and Sanes, 1985). We found that motor axons from spinal segment 8 reformed an apparently normal hindlimb innervation pattern even when transected near the plexus.…”

“…If regenerating axons are able to grow freely only in close proximity to their target muscles, the relatively large distances separating muscles in limbs of mature animals may make it impossible for the axons to express any intermuscular selectivity they may possess Wigston and Sanes, 1985). Hence, we cannot rule out the possibility that these regenerating axons could distinguish appropriate from inappropriate targets if given unimpeded access to both at close range.…”

Specificity of synaptic regeneration in the spinal cord of the larval sea lamprey.

“…In a few examples this appears to involve a degree of selective reinnervation of the post-synaptic targets. Examples include reinnervation of the neuromuscular junction of fish, amphibia, and mammals (Sperry & Arora, 1965 (however, see Scherer, 1986); Dennis & Yip, 1978;Wigston & Sanes, 1985), regeneration of sensory input onto spinal motor neurones in the bull-frog (Sah & Frank, 1984), reinnervation of autonomic ganglia in mammals (NjA, & Purves, 1977;Purves, Thompson & Yip, 1981), and the restoration of correct retinotectal projections in fish and amphibia (Attardi & Sperry, 1963;Fujisawa, 1981). Specificity has been suggested by some observations on synaptic regeneration of identified invertebrate neurones, both in vivo (Jansen & Nicholls, 1972) and in vitro (Fuchs, Nicholls & Ready, 1981).…”