Neural control of canine colon motor function: studies in vivo

The responses of the circular muscle of canine colon to stimulation of intrinsic nerves and to the probable mediators of these nerves were studied in vivo. In vivo studies were carried out using close intra-arterial injections and local field stimulation of proximal, mid-, and distal colon while recording circumferential contractions. Our results suggest that acetylcholine is the major excitatory mediator, but another excitatory mediator could be released by high frequency field stimulation after atropine. Norepinephrine had mixed inhibitory and excitatory effects, but no evidence was obtained that it was released by field stimulation. Substance P had mainly excitatory effects partly by a mechanism involving nerves and partly by a direct effect on muscle; it in addition to norepinephrine deserves further evaluation as the mediator of noncholinergic excitation to high frequency field stimulation. There is no explanation of the inhibition it produced after initial excitation during field stimulation. Vasoactive intestinal peptide had inhibitory effects but these were incomplete and inconsistent. This may be related to our inability to demonstrate relaxation or inhibition to field stimulation after atropine. Further evaluation of the possible role of vasoactive intestinal peptide and other agents as nonadrenergic, noncholinergic inhibitory mediators is required.     

Neural control of human motor development

It has been possible to expand considerably our understanding of human motor development by making a detailed analysis of various types of movement and muscular activation patterns during different stages of development. Alterations in development subsequent to the appearance of brain lesions have enabled valuable information to be collected about the underlying neural mechanisms, in addition to new information concerning the pathophysiology of cerebral palsy. Studies on the development of the corticospinal system indicate that plastic changes can take place after perinatal brain damage.     

Long-term preservation of canine bone marrow: in vitro studies.

In vitro studies were performed on canine bone marrow frozen with DMSO and stored in liquid nitrogen for 2 to 6 months. The results are compared with previously reported parallel in vivo experiments that demonstrated no loss of stem cells. When studies were performed immediately after thawing, there was no substantial drop in the count of nucleated cells and, except for megakaryocytes, there was no alteration of the bone marrow morphology. After two washes, and removal of DMSO, the nucleated cell count dropped to 50% of its previous value. Optic and electron microscopy showed severe damage in mature myeloid elements. In some instances, the cells had a condensed nucleus similar to the red-purple inclusion body of LE cells (as observed in systemic lupus erythematosus), and electron microscopy showed heavy chromatin clumping. On the other hand, both optic and electron microscopy showed a good preservation of lymphocytes, plasmocytes, and erythroid precursors. Two-hour DNA synthesis slightly dropped after storage, and this drop appeared more consistent when related to a constant volume of bone marrow (50 microliters) rather than to a constant number of nucleated cells (10(6)). In five instances frozen and thawed bone marrow was grown in short-term cultures, and analysis of 98 metaphases showed no major aberrations of the chromosomes and only 2% of minor aberrations, such as breakages and fragments. These data, compared with the results of previous in vivo experiments that showed no loss of stem cells after 5 months storage, suggest that stem cells are less sensitive to freezing and thawing injury than myeloid elements and/or that it might be safer for the thawed bone marrow not to be manipulated before infusion.     

Inhibitory motoneurons in arthropod motor control: organisation,function, evolution

Miniaturisation of somatic cells in animals is limited, for reasons ranging from the accommodation of organelles to surface-to-volume ratio. Consequently, muscle and nerve cells vary in diameters by about two orders of magnitude, in animals covering 12 orders of magnitude in body mass. Small animals thus have to control their behaviour with few muscle fibres and neurons. Hexapod leg muscles, for instance, may consist of a single to a few 100 fibres, and they are controlled by one to, rarely, 19 motoneurons. A typical mammal has thousands of fibres per muscle supplied by hundreds of motoneurons for comparable behavioural performances. Arthopods—crustaceans, hexapods, spiders, and their kin—are on average much smaller than vertebrates, and they possess inhibitory motoneurons for a motor control strategy that allows a broad performance spectrum despite necessarily small cell numbers. This arthropod motor control strategy is reviewed from functional and evolutionary perspectives and its components are described with a focus on inhibitory motoneurons. Inhibitory motoneurons are particularly interesting for a number of reasons: evolutionary and phylogenetic comparison of functional specialisations, evolutionary and developmental origin and diversification, and muscle fibre recruitment strategies.     

Opioid receptor agonists in the rabbit colon: comparison of in vivo and in vitro studies

Myoelectrical activity was recorded in the proximal and distal colon of rabbits using chronically implanted electrodes. The motility in both the proximal and distal colon was inhibited by the intravenous (IV) administration of the following opioid agonists for mu receptors: morphine and fentanyl, kappa receptors: ethylketazocine (EKC) and U 50 488 H, and delta receptors: D-Ala2 D-Leu5-enkephalin (DADLE) and D-Ser2 Leu-enkephalin-Thr6 (DSLET). In contrast, the myoelectric activity in the distal colon was increased during the infusion of an endogenous kappa opioid agonist, dynorphin (DYN). All of these effects were prevented by naloxone pretreatment. During in vitro studies using extraluminal force transducers, fentanyl, U 50 488 H and DSLET inhibited spontaneous contractions of the proximal colon, but U 50 488 H and DSLET caused a substantial increase in the motility of the distal colon. The observed motor responses in the proximal and distal colon following opioid agonist administration indicate that the control of these two intestinal segments may be different. It is suggested that the stimulatory effect of dynorphin on the distal colon is peripherally-mediated while inhibition of the whole colon by opioid agonists regardless of subtypes seems to be centrally-mediated.     

New concepts of cerebellar function in operative motor control and shaping of automatic motor behavior

Editor's Note. The following article broadens the scope of the "Discussion" section considerably. We would draw the reader's attention to the original article creating a new conception of cerebellar functional mechanisms, which complements critical reviews of published studies and authors' responses. We hope that this article will be of interest to the reader and that he will find this comprehensive survey useful.     

Neural control of circadian rhythms in plasma ACTH, plasma corticosterone and motor activity

The circadian rhythms for plasma ACTH and corticosterone (B), as well as motor activity, were explored in female rats after ocular enucleation (O-X), stereotaxic lesion of the suprachiasmatic nuclei (SCN-X) or of midbrain raphe nuclei (R-X), or both O-X and R-X, pharmacological blockade of the serotoninergic (5HT) system by pCPA, sometimes bypassed by 5-HTP, or 5-HT denervation of the SCN by local injection of 5,7-DHT. The three circadian rhythms explored responded quite differently to the treatments. In particular, the ACTH and B rhythms lost their usual close correlations. The amplitude and mean level of ACTH fluctuations were depressed after all treatments, but remained normal or were enhanced for B rhythm. ACTH rhythmicity actually was undetectable after SCN-X, pCPA and, in several rats, combined O-X and R-X, whereas persisting circadian and/or ultradian B and locomotor activity rhythms were always measured. The participation of the suprachiasmatic nuclei, the midbrain raphe nuclei and other possible 5-HT components in a complex circadian pacemaker system is discussed.     

Effect of arginine on angiogenesis induced by human colon cancer: in vitro and in vivo studies

This study investigated the effect of arginine (Arg) supplementation on angiogenesis in human colon cancer. The in vitro study investigated the effects of different Arg levels and inducible nitric oxide (iNO) synthase inhibitor on angiogenic protein expressions stimulated by SW480 cells. The results showed that the production of vascular endothelial growth factor (VEGF), basic fibroblast growth factor with 100 and 1000 μmol/L Arg and matrix metalloproteinase (MMP)-2 with 1000 μmol/L Arg was lower than that with 0 and 50 μmol/L Arg. Inhibition of iNO resulted in higher angiogenic protein expressions comparable with groups with low Arg administration, indicating that Arg administration at levels similar to or higher than physiological concentrations reduced the progression of colon cancer, and iNO may partly play a role in reducing angiogenesis. The in vivo study used a human colon cancer xenograft model in nude mice. Mice were inoculated with 1×10⁷ SW480 cells and assigned to two groups. The control group was fed a semipurified diet, while the experimental group was supplied an Arg-supplemented diet. After 5 weeks, tumors were harvested and spleens were excised for further analysis. Results showed that the MMP-2, MMP-9 and VEGF receptor levels in tumors were significantly lower, whereas tumor NO levels and spleen natural killer (NK) cell activities were higher in the Arg group than in the control group. These results were consistent with the in vitro study that dietary Arg supplementation inhibits the progression of colon cancer possibly by increasing NO secretion and consequently enhancing NK cell activity.     

Neural integration of movement: role of motor cortex in reaching

The study of the motor cortex in behaving monkeys during the past 20 years has provided important information on the brain mechanisms underlying motor control. With respect to reaching movement in space, a key role of motor cortex in specifying the direction of reaching has been proposed on the basis of results from studies of the activity of cells and cell populations during reaching. These results and ideas are reviewed and discussed in the context of recent findings concerning the spinal mechanisms underlying reaching movements.     

Red nucleus: role in motor control

Experimental reports in the past year have provided a better understanding of the motor functions of excitatory and inhibitory neurotransmitters in the red nucleus, and of the sensorimotor properties of single rubral neurons. These data fit well within the framework of a neural network model of the rubrocerebellar system.     

In vitro modulation of canine polymorphonuclear leukocyte function by granulocyte-macrophage colony stimulating factor

Granulocyte-macrophage colony stimulating factor (GMCSF) promotes the growth of granulocytes and macrophages from undifferentiated bone marrow cells and modulates the oxidative responses of polymorphonuclear leukocytes (PMN) to endogenous chemoattractants. We found that,in vitro, naturally occurring glycolsylated human GMCSF does not disturb the resting canine PMN membrane potential, may attentuate PMN oxidative responses to PMA, and is, to a small degree, chemotaxigenic. GMCSF, however, inhibits PMN chemotaxis to zymosanactivated plasma (ZAP). Compared to temperature controls, GMCSF (1-100 U/ml) produced up to 1.5-fold increases in H₂O₂ production after 15 minutes, while phorbol myristate acetate (PMA) treated cells increased H₂O₂ production 8–12-fold after 15 minutes. Preincubation of cells with GMCSF (1–100 U/ml) prior to PMA stimulation significantly reduced the H₂O₂ levels induced by PMA. H202 production was inhibited up to 15% after 15 minutes of GMCSF preincubation and up to 40% after 60 minutes of preincubation. As a chemotaxigenic agent, GMCSF (10–1000 U/ml) was able to elicit 49%–102% increases in quantitative cellular migration, compared to random migration. Total cellular chemotaxis to GMCSF was < 30% of the response to ZAP. Preincubation of PMNs with GMCSF for 15 minutes significantly inhibited ZAP-induced cellular migration. Human GMCSF does not appear to activate canine PMNin vitro and may actually down-regulate PMN inflammatory responses.Supported by the Armed Forces Radiobiology Research Institute, Defense Nuclear Agency, under work unit No. 00082. Views presented in this paper are those of the authors; no endorsement by the Defense Nuclear Agency has been given or should be inferred. Research was conducted according to the principles enunciated in the Guide for the Care and Use of Laboratory Animals prepared by the Institute of Laboratory Animal Resources, National Research Council.     

Dentate control pathways of cortical motor activity. Anatomical and physiological studies in rat: comparative considerations

The dentato-thalamocortical projections have been studied in albino rats using anatomical and physiological approaches. The anatomical analysis reveals that the dentatothalamic input to the ventral thalamus and the thalamocortical projection from this region onto the motor cortical area have a complex topographical arrangement. The corticothalamic reverberating pathways, both direct and through a relay in the nucleus reticularis thalami, are also roughly arranged in register with the same topographical pattern. This arrangement has been reconciled with that of the motor cortex, as determined by the motor effects of intracortical microstimulations. From this is inferred a somatotopical arrangement of the cerebellar nucleus lateralis, or dentate. These observations are confirmed by the results of our physiological analysis. The movements obtained with direct microstimulations of the nucleus lateralis affect either one joint (simple movements) or, more seldom, several joints (complex movements) of the same limb. A rough rostrocaudal arrangement is found in the nucleus lateralis: the caudocentral regions of the nucleus contain the representation of the musculature of forelimb and head, whereas the hindlimb is represented in the rostralmost part of the nucleus. A more complex organization is found to be related to the three cytoarchitectonic subdivisions of the nucleus lateralis. The main, large-celled part of the nucleus is engaged in the control of the large skeletal musculature. The dorsolateral hump is involved in mouth and peri-oral activities. The ventral, parvocellular, subnucleus is involved in fine exploratory movements of vibrissae, eyes, and forelimb wrist and fingers. The implication of the dentato-thalamocortical pathways in the cortical motor activities in the rat is discussed with attention to the dentate control of the "voluntary" motricity in primates.