Biomedical subjects

Douglas G Stuart

Publications and source records attributed to Douglas G Stuart.

9 recordsLinked to original sources

PubMed2007

Does motoneuron adaptation contribute to muscle fatigue?

To help reduce the gap between the cellular physiology of motoneurons (MNs) as studied "bottom-up" in animal preparations and the "top-down" study of the firing patterns of human motor units (MUs), this article addresses the question of whether motoneuron adaptation contributes to muscle fatigue. Findings are reviewed on the intracellularly recorded electrophysiology of spinal MNs as studied in vivo and in vitro using animal preparations, and the extracellularly recorded discharge of MUs as studied in conscious humans. The latter "top-down" approach, combined with kinetic measurements, has provided most of what is currently known about the neurobiology of muscle fatigue, including its task and context dependencies. It is argued that although the question addressed is still open, it should now be possible to design new "bottom-up" research paradigms using animal preparations that take advantage of what has been learned with the use of relatively noninvasive quantitative procedures in conscious humans.

Action Potentials↗

PubMed2006

The academic lineage of Sir John Carew Eccles (1903-1997).

This report reviews the academic lineage of Sir John Eccles; who trained him, whom he then trained and with whom he collaborated, and the subsequent impact of his trainees and collaborators on neuroscience and other areas. In a post-training career at five institutions in four countries (Great Britain, Australia, New Zealand, back to Australia, USA) and during retirement in Switzerland, Eccles trained and collaborated with over 180 people (mostly neuroscientists) from 21 countries. Most of them have had stellar research and training records that span the cellular-behavioral-philosophical spectrum of neuroscience, with a focus from peripheral neuromuscular issues to the forebrain. Some have been equally distinguished in other areas of biomedical science. Eccles' academic contributions and lineage are a valuable colloquium topic in a neuroscience training program. His experimental work spanned much of the 20th C before the recent emphasis on the application of the techniques of molecular biology. He continually sought to integrate information from the cellular to the systems and behavioral levels of analysis and synthesis. He also devoted a substantial amount of his intellectual effort to the mind-brain and other philosophical issues. Eccles' prodigious working hours and enthusiasm for his projects were a role model for such trainees. Hard-working trainees often ask how can they retain their all-round interests, and indeed their humanity and citizenry, as they focus more and more on their necessarily narrowly focused neuroscience research. Again, Eccles' writings and overall behavior show that it can indeed be done, but only by the application of extraordinary effort and dedication.

Academic Medical Centers↗

PubMed2005

Integration of posture and movement: contributions of Sherrington, Hess, and Bernstein.

Neural mechanisms that integrate posture with movement are widespread throughout the central nervous system (CNS), and they are recruited in patterns that are both task- and context-dependent. Scientists from several countries who were born in the 19th century provided essential groundwork for these modern-day concepts. Here, the focus is on three of this group with each selected for a somewhat different reason. Charles Sherrington (1857-1952) had innumerable contributions that were certainly needed in the subsequent study of posture and movement: inhibition as an active coordinative mechanism, the functional anatomy of spinal cord-muscle connectivity, and helping set the stage for modern work on the sensorimotor cortex and the corticospinal tract. Sadly, however, by not championing the work of his trainee and collaborator, Thomas Graham Brown (1882-1965), he delayed progress on two key motor control mechanisms: central programming and pattern generation. Walter Hess (1881-1973), a self-taught experimentalist, is now best known for his work on CNS coordination of autonomic (visceral) and emotional behavior. His contributions to posture and movement, however, were also far-reaching: the coordination of eye movements and integration of goal-directed and "framework" (anticipatory set) motor behavior. Nikolai Bernstein (1896-1966), the quintessence of an interdisciplinary, self-taught movement neuroscientist, made far-reaching contributions that were barely recognized by Western workers prior to the 1960s. Today, he is widely praised for showing that the CNS's hierarchy of control mechanisms for posture and movement is organized hand-in-hand with distributed and parallel processing, with all three subject to evolutionary pressures. He also made important observations, like those of several previous workers, on the goal focus of voluntary movements. The contributions of Sherrington, Hess, and Bernstein are enduring. They prompt thought on the philosophical axioms that appear to have driven their research, and the continual need for emphasis on interdisciplinary, comparative, and transnational approaches to advance movement neuroscience.

Affect↗

PubMed2005

Slow-tonic muscle fibers and their potential innervation in the turtle, Pseudemys (Trachemys) scripta elegans.

A description is provided of the ratio of slow-tonic vs. slow- and fast-twitch fibers for five muscles in the adult turtle, Pseudemys (Trachemys) scripta elegans. The cross-sectional area of each fiber type and an estimation of the relative (weighted) cross-sectional area occupied by the different fiber types are also provided. Two hindlimb muscles (flexor digitorum longus, FDL; external gastrocnemius, EG) were selected on the basis of their suitability for future motor-unit studies. Three neck muscles (the fourth head of testo-cervicis, TeC4; the fourth head of retrahens capitus collique, RCCQ4; transversalis cervicis, TrC) were chosen for their progressively decreasing oxidative capacity. Serial sections were stained for myosin adenosine triphosphatase (ATPase), NADH-diaphorase, and alpha-glycerophosphate dehydrogenase (alpha-GPDH). Conventional fiber-type classification was then performed using indirect markers for contraction speed and oxidative (aerobic) vs. glycolytic (anaerobic) metabolism: i.e., slow oxidative (SO, including slow-twitch and possibly slow-tonic fibers), fast-twitch, oxidative-glycolytic (FOG), and fast-twitch glycolytic (Fg) fibers. Slow-tonic fibers in the SO class were then revealed by directing the monoclonal antibody, ALD-58 (raised against the slow-tonic fiber myosin heavy chain of chicken anterior latissimus dorsi), to additional muscle cross sections. All five of the tested muscles contained the four fiber types, with the ATPase-stained fibers including both slow-tonic and slow-twitch fibers. The extreme distributions of SO fibers were in the predominately glycolytic TrC vs. the predominately oxidative TeC4 muscle (TrC-SO, 9%; FOG, 20%; Fg, 71% vs. TeC4-SO, 58%: FOG, 16%; Fg, 25%). Across the five muscles, the relative prevalence of slow-tonic fibers (4-47%) paralleled that of the SO fibers (9-58%). TeC4 had the highest prevalence of slow-tonic fibers (47%). The test muscles exhibited varying degrees of regional concentration of each fiber type, with the distribution of slow-tonic fibers paralleling that of the SO fibers. In the five test muscles, fiber cross-sectional area was usually ranked Fg > FOG > SO, and slow-twitch always > slow-tonic. In terms of weighted cross-sectional area, which provides a coarse-grain measure of each fiber type's potential contribution to whole muscle force, all five muscles exhibited a higher Fg and lower SO contribution to cross-sectional area than suggested by their corresponding fiber-type prevalence. This was also the case for the slow-twitch vs. slow-tonic fibers. We conclude that slow-tonic fibers are widespread in turtle muscle. The weighted cross-sectional area evidence suggested, however, that their contribution to force generation is minor except in highly oxidative muscles, with a special functional role, like TeC4. There is discussion of: 1) the relationship between the present results and previous work on homologous neck and hindlimb muscles in other nonmammalian species, and 2) the potential motoneuronal innervation of slow-tonic fibers in turtle hindlimb muscles.

Animals↗

PubMed2004

Fatigue of rat hindlimb motor units: biochemical-physiological associations.

Associations between fatigability and biochemical properties within motor unit (MU) types were explored in two hindlimb muscles of the adult rat. Type FF MUs in extensor digitorum longus and type S units in soleus were subjected either to a moderate (type FF) or severe (type S) 6-min, fatigue-inducing stimulation protocol. For both MU types, the range of values for their fatigability was considerably greater than the ranges in the activity levels of three enzymes in the units' constituent muscle fibers (MFs). These enzymes represented major energy-yielding pathways: adenylokinase, for high-energy phosphate metabolism; lactate dehydrogenase, for anaerobic glycolysis; and malate dehydrogenase, for oxidative metabolism. There were also relatively weak associations between the fatigue indices of the MUs and the activity levels of the three enzymes. Thus, this work supports previous conclusions that the force decline exhibited by MUs during electrically evoked contractions depends on both MF biochemistry and other intracellular mechanisms. Electromyographic measurements suggested that these other mechanisms are distal to the intramuscular branches of the axon in type FF units, and distal to excitation-contraction coupling in type S units.

Action Potentials↗

PubMed2002

Associations between the morphology and physiology of ventral-horn neurons in the adult turtle.

This study compared some morphologic and physiological properties of adult turtle spinal motoneurons (MNs) vs. interneurons (INs). Reconstructions were made of 20 biocytin-stained cells, which had been previously studied physiologically in 2-mm-thick slices of lumbosacral spinal cord. The intracellularly measured physiological properties included resting potential, input resistance (R(N)), threshold (rheobase, I(Rh)), and slope of the stimulus current (I) -spike frequency (f) relation. The seven morphologic properties that were quantified for each cell included three indices of somal size (diameter, area, volume), and four of dendritic size: the number of first- and last-order branches, rostrocaudal extent, and sigma individual lengths. Significant differences were shown between all seven morphologic parameters for MNs vs. INs. Despite the small sample size, significant differences were also shown for five of seven parameters for high-threshold vs. low-threshold MNs, and three of seven for low-threshold MNs vs. INs. These latter three parameters were the number of terminal dendritic branches, their rostrocaudal extent, and the sigma dendritic lengths. Linear associations for the MN + IN and the MN samples were stronger between the four dendritic parameters than between soma-dendritic ones. Exponential associations between morphologic and physiological properties were mostly significant (28 of 30), and their strength was in the order I(Rh) < R(N) < f/I slope for the MN +IN sample and I(Rh) < R(N) = f/I slope for the MN sample. There is discussion of the relevance of the above findings to the provisional classification of turtle ventral-horn neurons on the basis of electrophysiology alone.

Action Potentials↗

PubMed2002

Motoneurons: A preferred firing range across vertebrate species?

The term "preferred firing range" describes a pattern of human motor unit (MU) unitary discharge during a voluntary contraction in which the profile of the spike-frequency of the MU's compound action potential is dissociated from the profile of the presumed depolarizing pressure exerted on the unit's spinal motoneuron (MN). Such a dissociation has recently been attributed by inference to the presence of a plateau potential (PP) in the active MN. This inference is supported by the qualitative similarities between the firing pattern of human MUs during selected types of relatively brief muscle contraction and that of intracellularly stimulated, PP-generating cat MNs in a decerebrate preparation, and turtle MNs in an in vitro slice of spinal cord. There are also similarities between the stimulus-response behavior of intracellularly stimulated turtle MNs and human MUs during the elaboration of a slowly rising voluntary contraction. This review emphasizes that there are a variety of open issues concerning the PP. Nonetheless, a rapidly growing body of comparative vertebrate evidence supports the idea that the PP and other forms of non-linear MN behavior play a major role in the regulation of muscle force, from the lamprey to the human.

Animals↗

PubMed2002

Reflections on spinal reflexes.

Over the past four decades, the understanding of proprioceptive spinal reflexes has advanced far more rapidly than generally considered. This problem could be largely obviated in undergraduate and graduate training programs if the topic of reflexes was introduced subsequent to the concept and mechanisms of pattern generation within the central nervous system. The key advantage would then be that the neuroscience community as a whole would gain appreciation of the fact that proprioceptive reflexes are not hard-wired but rather are context- and phase-dependent, with the central nervous system selecting input-output pathways appropriate for the task at hand.

Animals↗

PubMed2002

Effects of excitatory modulation on intrinsic properties of turtle motoneurons.

The purpose of this study was to quantify the effects of excitatory modulation on the intrinsic properties of motoneurons (MNs) in slices of spinal cord taken from the adult turtle. Responses were noted following application of an excitatory modulator: serotonin (5-HT), muscarine, trans-1-amino-1,3-cyclopentane dicarboxylic acid (tACPD), or all three combined. A sample of 44 MNs was divided into 2 groups, on the basis of whether MNs did (28/44) or did not (16/44) demonstrate a nifedipine-sensitive acceleration of discharge during a 2-s, intracellularly injected stimulus pulse. Such acceleration indicates the development of a plateau potential (PP). Excitatory modulation lowered the MNs' resting potential, increased input resistance, decreased rheobase, reduced several afterhyperpolarization values, and shifted the conventional, one-phase stimulus current-spike frequency (I-f) relation to the left. For both MN groups, the relative efficacy of excitatory modulation on both non-PP and PP MNs was generally in the following order: combined application > 5-HT approximately muscarine > tACPD. In many instances, the effects of modulation differed significantly for non-PP versus PP MNs, the most pronounced being in their I-f relation. To describe this difference, it was necessary to measure a two-phase relation. In PP MNs, excitatory modulation considerably increased the slope of the first (initial) phase and flattened the second (later) phase of this relation. The latter result bore similarities to that obtained in a previous study, which addressed MN firing behavior during fictive locomotion of the high-decerebrate cat.

Animals↗