Elspeth M. McLachlan

The segmental origin of preganglionic axons in the upper thoracic rami of the cat

Sympathetic preganglionic neurones have been identified in the thoracic spinal cord of cats after selective application of horseradish peroxidase (HRP) to the cut axons of the individual white rami of T1 to T3. The labelled neurones were restricted rostrocaudally to the length of a single segment, although this did not correspond exactly with the point of exit of the corresponding spinal root. The results do not support the concept of an intraspinal pathway of preganglionic axons in this region and one possible explanation for the difference between these data and those of others is discussed.

RAPID ATROPHY OF MOUSE SOLEUS MUSCLES AFTER TENOTOMY DEPENDS ON AN INTACT INNERVATION

Changes in length and mass of mouse soleus muscles have been determined during the first 14 days after division of the Achilles tendon and/or the tibial nerve. Muscle atrophy and associated histological changes were detectable 24 h after tenotomy, and increased progressively over the first week. These changes were less marked in muscles which had also been denervated, and were rapidly reversed if the tendon became reattached. An attempt is made to distinguish the role of the nerve supply from the effects of reduced longitudinal tension in the production of atrophy after tenotomy.

Rapid adjustment of sarcomere length in tenotomized muscles depends on an intact innervation

Mean sarcomere length has been determined by laser diffraction in fibres of mouse soleus muscle at various times after division of the proximal tendon. Sarcomere length was initially reduced by 27% but was normal from 7 days after tenotomy. Initial shortening was less but recovery slower if the muscle was also denervated. Sarcomere length did not recover by 14 days if the tendon was cut soon after the muscle fibres became reinnervated after nerve section. It is suggested that afferent nervous pathways are involved in the short-term adjustment of sarcomere length to fibre length.

Atrophic effects of proximal tendon transection with and without denervation on mouse soleus muscles

The response of mouse soleus muscles to transection of the proximal tendon was examined at both gross and microscopic levels. Changes in length and mass of the muscle, and in the dimensions, number, and ATPase staining characteristics of the muscle fibers, were determined at various times to 4 to 6 weeks after tenotomy. Muscles shortened by more than 50% and lost about 60% of their mass. Fiber cross-sectional area increased, and then decreased and stabilized below control after 7 days, and degenerative lesions appeared in some fibers. Fiber numbers decreased by nearly 20% and then remained constant, apparently by regeneration of new fibers replacing atrophied ones. The proportion of muscle fibers of the slow-twitch type was reduced. No structural or functional changes in motor nerve terminals could be detected, except for detachment from severely atrophied fibers. Concurrent denervation decreased both shortening and the loss of mass after tenotomy. Fiber diameter decreased but no significant degenerative lesions or loss of fibers could be detected. Fiber-type composition was unchanged. These experiments provide quantitative information about the degenerative changes in tenotomized muscles without the variable complications arising from tendon reattachment. Comparison of the responses with those that follow transection of the Achilles tendon shows that the degree of atrophy is independent of the extent of active muscle shortening after tenotomy.

Dopaminergic neurons in sympathetic ganglia of the dog

A study has been made of the catecholamine content of various canine sympathetic ganglia. The data have been related to the anatomical location of ganglion cells supplying the kidney and hindpaw. Retrograde transport of horseradish peroxidase from filaments of the renal nerve labelled cell bodies in the ipsilateral renal and superior mesenteric ganglia and in one to three contiguous ganglia of the lower thoracic paravertebral chain. In most prevertebral and paravertebral ganglia, the ratio of the tissue level of dopamine (DA) to that of noradrenalin (NA) lay between 3 and 7%. The relative DA levels were significantly higher (DA: NA = 8–20%) in one to three paravertebral ganglia of the lower thoracic and the sacral regions. In some animals, the relative DA levels in renal and/or coeliac and superior mesenteric ganglia were also greater than the mean paravertebral values for these individuals. Reserpine pretreatment depleted DA and NA stores and abolished or substantially reduced catecholamine fluorescence in all ganglia. After reserpine pretreatment followed by administration of a monoamine oxidase inhibitor and l─DOPA, fluorescence was restored to some neurons in ganglia corresponding to those normally having raised DA levels. This local restoration of fluorescence was correlated with a dramatic increase in the relative amount of DA in equivalent contralateral ganglia (DA: NA = 50–280%). These results suggest that: (i) some catecholamine-containing ganglion cells are distinct from sympathetic noradrenergic neurons in their high content of DA and their ability to bind dopamine following reserpine-induced depletion, and (ii) these neurons are relatively restricted in their distribution, lying between T8 and L1 and L7 and S2 of the paravertebral chain and in some prevertebral ganglia. They occur at locations in which ganglion cells projecting to the kidney and the hindlimb are likely to be represented. Our results are consistent with pharmacological evidence that has been presented elsewhere that renal juxtaglomerular vessels and arteriovenous shunts of the hindpaw are supplied by dopaminergic dilator axons. They also suggest that some other peripheral effectors in the upper abdomen may be innervated by dopaminergic axons.

Modification of the atrophic effects of tenotomy on mouse soleus muscles by various hind limb nerve lesions and different levels of voluntary motor activity

The response of mouse soleus muscles to transection of the proximal tendon was examined in a variety of circumstances which might be expected to modify the amount of activation of soleus motoneurons. (i) Denervation of ankle flexors antagonistic to the soleus produced slight atrophy of intact muscles but protected soleus to some extent from the effects of concurrent tenotomy. The onset of changes in tenotomized fibers was delayed several days. (ii) Tenotomy of the soleus soon after reinnervation of the muscle fibers (following tibial nerve transection) resulted in little loss of mass and no degenerative changes. (iii) Denervation during the first few days after tenotomy halted the progress of muscle shortening and alleviated the atrophic changes at the stage reached at the time of denervation. Anesthesia without surgical intervention at the same period after tenotomy also halted the atrophic changes, despite subsequent muscle shortening. (iv) Oral administration of diazepam (approximately 1 mg/kg/day) or chlorpromazine (approximately 12 mg/kg/day), which decreased motor activity during the early posttenotomy period, reduced the amount of muscle shortening and the degree of atrophy. The results suggest that both reflex and voluntary activation of soleus motoneurons contribute to the development of atrophy after tenotomy. The response in soleus muscle seems to be particularly sensitive to the pattern of motor activity during the first 2 to 3 days after tenotomy.

A mechanism for the observed recovery from ineffectiveness of synapses in the central nervous system

Three recent experiments have shown that synaptic connections in the central nervous system that are structurally present but functionally ineffective can be made to recover their effectiveness for exciting neurons. The common features of these experiments are briefly reviewed. A mechanism is proposed requiring three postulates that are each consistent with orthodox physiology. There is an opportunity for a quantitative treatment to test against future experimental results.