Repeated, intense, cutaneous stimulation results in the gradual development of inhibition of spinal interneurones. This change in neuronal activity could not be demonstrated in rats whose spinal cords had been transected, and was considered to be the consequence of supraspinal mechanisms. . Experiments sere carried out to determine which areas of the brain were involved. Unitary recordings from neurones situated in nucleus reticularis pontis-caudalis, nucleus reticularis giganto-cellularis, nucleus reticularis parvocellularis and nucleus medulla oblongata pars ventralis demonstrated a progressively increasing excitatory response to repeated intense cutaneous stimulation. These areas were shown to have direct projections to the spinal cord, by retrograde transport of horseradish peroxidase. Cells in nucleus reticularis gigantocellularis, which demonstrated a progressively increasing excitatory response, could also be antidromically activated from the spinal cord. Repeated stimulation of some of these areas produced a progressive inhibition of spinal interneurones which was similar to that resulting from cutaneous stimulation. It would appear that nucleus reticularis gigantocellularis and nucleus reticularis pontis-caudalis are involved in the development of a progressive inhibition of spinal interneurones. A similar role for other reticular and raphe nuclei can not be excluded on the basis of evidence presently available. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

It is known that nerves are particularly critical during the early or dedifferentiative phase of limb regeneration. During this period in the innervated limb, cells just proximal to the amputation surface dedifferentiate, migrate to the limb tip, and undergo mitosis. These processes give rise to a population of undifferentiated mesenchymatous cells capable of redifferentiating into the missing components of the newly forming regenerate. The consequences of denervation stand in stark contrast to the normal events occurring in the innervated limb, because neither a blastema nor a regenerate forms. Results from this study indicate that during the early portion of the dedifferentiative phase in regenerates less than 2 3/4, days old the nerve apparently has little or no effect on the internal stump tissues. Of considerable interest in this regard is this study's documentation of a lack of neural influence on DNA synthesis and thus the cell cycle during the early dedifferentiative phase. Subsequently, during a transition period represented by 2 3/4 to 5 1/2 days regenerates there is some evidence for a neural influence on DNA synthesis in cells of the limb stump. Finally, on days 6 through 8, DNA synthesis is clearly nerve dependent. Since DNA synthesis is a prerequisite for mitosis, the depressed synthesis in a denervated limb precludes mitotic activity during the nerve-dependent, later portion of the dedifferentiative phase. Therefore, this research supports the idea that during the late dedifferentiative phase, including mound and early cone blastemal stages, there is a neural influence on the G1 or S phases of the cell cycle. This conclusion thereby makes progress toward explaining earlier observations of depressed mitotic activity during this period.

In the field of spinal-cord neurophysiology, the nature of and the rules which govern the strength of functional connections between muscle afferents and motoneurons supplying the same muscle are important to delineate. This study addressed a facet of this issue by testing the possibility that the strength of the spindle Ia-motoneuronal connections is stronger (as demonstrated by the differing amplitudes of the mean maximum composite Ia EPSPs) if both neurons supply the same sub-volume of the muscle, providing the various sub-volumes of the muscle are capable of independent action. Intracellular recordings were made of the Ia EPSP responses of semimembranosus (SM) and lateral gastrocnemius (LG) motoneurons in anesthetized low-spinal cats to electrical stimulation (Group I range) of nerve branches supplying different parts of the homonymous muscle, as well as different heteronymous muscles. For study of SM motoneurons, stimulated nerve branches included those supplying the anterior (SMa) and posterior (SMp) heads of the SM muscle and three providing heteronymous input from the anterior (BFa) and posterior (BFp) parts of biceps femoris and the distal part of the semitendinosus (STd) muscle. Ia EPSPs were partitioned such that stimulation of the SMa nerve branch produced significantly larger EPSPs in SMa motoneurons than in SMp cells; likewise, stimulation of the SMp nerve branch produced larger EPSPs in SMp motoneurons than in SMa cells. Study of the differences in the strength of heteronymous Ia input (i.e., from BFa, BFp and STd) between the SMa and SMp cell groups correlates with the different actions reported previously for the two heads of the SM muscle. For study of LG motoneurons, the stimulated nerve branches were those supplying the four neuromuscular compartments of the LG muscle (LG1, LG2, LG3 and LGm) and the nerve to a heteronymous muscle, soleus (SOL). In all five instances, partitioned Ia effects were evident. An association is suggested between the present results and previous electromyographic studies. The previous studies have shown that the muscle heads (SM) or neuromuscular compartments (LG) under consideration in this study are capable of somewhat separate actions. The present study also included assessment of the relative extent to which the partitioned Ia effects could be attributed, in part, to one or two developmental factors, topographic specificity and species specificity. The analysis suggested that both factors were potentially implicated, with species specificity somewhat predominant over topographic specificity.

published_or_final_version / Molecular Biology / Doctoral / Doctor of Philosophy

published_or_final_version / Physiology / Master / Master of Philosophy

published_or_final_version / Biochemistry / Master / Master of Philosophy

The effects of capsaicin, the major pungent component of hot peppers, were assessed on neuropeptide levels and on sensory function in neonatal and adult rats and in adult guinea pigs. Systemic doses of capsaicin in rats treated while neonates or while adults produced marked depletion of substance P (SP) in dorsal roots plus ganglia (DRG) and in dorsal spinal cord without altering tail-flick latencies in the treated animals. Guinea pigs had several-fold higher levels of SP than did rats in DRG and dorsal cord. In adult guinea pigs, systemic doses of capsaicin as low as 2.5 mg/kg depleted SP in DRG while a 10 mg/kg dose depleted the peptide maximally in DRG (85% decrease) and in the dorsal cord (35% decrease). High doses of capsaicin in guinea pigs had no consistent effects on levels of radioimmunoassayable cholecystokinin (CCK), vasoactive intestinal polypeptide, or somatostatin although a transient decrease in CCK levels was observed four days after dosing in DRG and in ventral cord. A single 5 mg/kg dose of capsaicin rendered animals completely insensitive to chemical irritation of the cornea without affecting sensitivity to noxious heat. Higher doses of capsaicin produced a marked insensitivity to nociceptive and non-nociceptive heat as well as to chemical irritation without affecting other sensory modalities. The SP depletion and sensory deficits produced by a single 50 mg/kg dose of capsaicin were still evident ten weeks later. The pattern of selectivity of the sensory deficits produced by capsaicin differed from that produced by morphine which was active against all forms of nociceptive stimuli. High doses of capsaicin also induced skin lesions and corneal opacities in guinea pigs. The syndrome of sensory effects produced by capsaicin in guinea pigs closely resembles the pattern of sensory deficits in familial dysautonomia, an autosomal recessive disorder in which there is a disappearance of SP from the substantia gelatinosa of the spinal cord. The results indicate that in the guinea pig capsaicin is potent at producing a unique, long-lasting syndrome of peripheral sensory deficits that may result from an action of the compound on SP-containing primary afferent neurons. Capsaicin is a valuable pharmacological tool for investigation of the neurochemistry and neurophysiology of primary afferent neurons and animals treated with the agent may be useful laboratory models of some forms of peripheral neuropathy.

No description available.

No description available.

No description available.