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Biomedical subjects

T A Sears

Publications and source records attributed to T A Sears.

At least 91 records · Page 5Linked to original sources

Internodal conduction in undissected demyelinated nerve fibres.

1. A new method is described for recording external longitudinal currents from single undissected nerve fibres in rat ventral roots. The method permits identification of the sites of fifteen or more successive nodes of Ranvier in a given single fibre and the measurement of internodal conduction times between them.2. Average internodal conduction time for normal ventral root fibres of internodal length between 0.75 and 1.45 mm is 19.7 +/- 4.6 (S.D.) musec at 37 degrees C. Internodal conduction time appeared to show a minimum for fibres of internodal length 1.0 mm.3. Ventral roots were demyelinated by focal application of diphtheria toxin. Although conduction is markedly slowed in demyelinated fibres, sites of inward membrane current remain spatially separated indicating that conduction remains saltatory to the point of conduction block rather than becoming continuous as in unmyelinated fibres.4. Slowing of conduction appears to be due to changes in the passive electrical properties of the internodal myelin. Evidence is presented suggesting that there is an increase in internodal capacitance and a decrease in internodal transverse resistance at internodes of demyelinated fibres; such changes would have the effect of delaying excitation at the nodes. The changes in passive electrical properties, which appear to be primarily in the vicinity of the nodes, would be consistent with the pathological changes observed in demyelinated fibres.5. Internodal conduction times in demyelinated fibres have ranged from normal (26 musec at 30 degrees C) to more than 600 musec. There is a great variation in internodal conduction time at successive internodes of a given single fibre; this presumably reflects the varying severity of demyelination of successive internodes.6. As in normal fibres, nodes of demyelinated fibres generate less current when excited by the second of two closely spaced impulses. This results in an increased internodal conduction time for the second impulse and, at a critically short interstimulus interval, conduction block of the second impulse.7. The increased refractory period of transmission of internodes with increased internodal conduction times is a consequence of the decreased ability of such internodes to sustain propagation in the face of small decreases in nodal current.8. During tetanic stimulation, increases in internodal conduction time are associated with corresponding decreases in nodal current generated by the node proximal to the internode in question.9. It is suggested that changes in the magnitude of the nodal current during repetitive activity are due to changes in transmembrane concentration gradients of sodium, the increased internodal conduction time and eventual conduction block during tetanic stimulation being caused by intracellular sodium accumulation.10. Intracellular sodium accumulation is also offered as the explanation for the post-tetanic depression seen in demyelinated fibres.

Action Potentials↗

The form and distribution of the surface evoked responses in cerebellar cortex from intercostal nerves in the cat.

1. The form and distribution of the cerebellar evoked responses to electrical stimulation of intercostal and other thoracic segmental nerves were investigated in anaesthetized cats.2. Low intensity stimulation (< 2 x nerve threshold) evoked short latency, low amplitude (< 20 muV), initially surface positive responses which could only be distinguished with certainty from the electrocorticogram with averaging.3. On the basis of experiments involving sectioning of afferent tracts it is concluded that intercostal evoked responses of less than 7.0 msec latency are conducted in dorsal spino-cerebellar, ventral spino-cerebellar and dorsal column (cuneo-cerebellar) pathways.4. The surface positive waves have a highly punctate distribution with a steep potential gradient extending over an area of about 1 mm diameter. It is postulated that these small fields represent activation of single or few mossy fibre inputs.5. Short latency responses to thoracic inputs were found only in the ipsilateral intermediate cortex and lateral margin of the vermis of the anterior lobe (lateral two thirds of Larsell's lobules IV and V of the accessible cortex). The responses were distributed throughout the fore and hind limb areas of the anterior lobe and no rostro-caudal or medio-lateral segmental organization was seen.6. It is suggested that the overlapping distribution of thoracic and fore and hind limb mossy fibre inputs within the cerebellar cortex provides an anatomical basis for the integration of information from the trunk and from the limbs.

Animals↗

Spinal integration of segmental, cortical and breathing inputs to thoracic respiratory motoneurones.

1. The spinal integration of cortical, segmental and breathing inputs to thoracic motoneurones was studied in anaesthetized, paralysed cats: the breathing input was intensified by underventilation or abolished by hyperventilation.2. In apnoeic animals, low intensity stimulation of an internal intercostal nerve evoked a brief latency polysynaptic reflex discharge of expiratory motoneurones (direct response) in several adjacent segments with no or little response of the inspiratory motoneurones.3. A similar direct response of expiratory motoneurones occurred with brief tetanic stimulation of the trunk area in the contralateral sensorimotor cortex.4. Conditioning of an intercostal-intercostal test reflex by a prior stimulus to an intercostal nerve or to the cortex gave conditioning curves showing facilitation of transmission to expiratory motoneurones at short intervals (5-25 msec) and inhibition at long intervals (25-200 msec).5. The direct response of expiratory motoneurones to the cortical or segmental inputs was depressed during the inspiratory phase when the animal was underventilated; conversely the spontaneous activity of the inspiratory motoneurones was inhibited for a period that corresponded with the direct response or to the phase of facilitated transmission to expiratory motoneurones. During the expiratory phase, the cortically or segmentally induced direct response was facilitated but the inhibition of inspiratory motoneurone activity was concealed by the absence of spontaneous activity.6. It was possible with discrete lesions of the spinal cord to differentiate between the pathways subserving the responses to cortical stimulation and the spontaneous activity due to the breathing input.7. To account for the results a working hypothesis is proposed utilizing a segmental interneuronal network which transmits mutual reciprocal inhibition between inspiratory and expiratory motoneurones.

Animals↗

The proprioceptive reflex control of the intercostal muscles during their voluntary activation.

1. A quantitative study has been made of the reflex effects of sudden changes in mechanical load on contracting human intercostal muscles during willed breathing movements involving the chest wall. Averaging techniques were applied to recordings of electromyogram (EMG) and lung volume, and to other parameters of breathing.2. Load changes were effected for brief periods (10-150 msec) at any predetermined lung volume by sudden connexion of the airway to a pressure source variable between +/- 80 cm H(2)O so that respiratory movement could be either assisted or opposed. In some experiments airway resistance was suddenly reduced by porting from a high to a low resistance external airway.3. Contracting inspiratory and expiratory intercostal muscles showed a ;silent period' with unloading which is attributed to the sudden withdrawal from intercostal motoneurones of monosynaptic excitation of muscle spindle origin.4. For both inspiratory and expiratory intercostal muscles the typical immediate effect of an increase in load was an inhibitory response (IR) with a latency of about 22 msec followed by an excitatory response (ER) with a latency of 50-60 msec.5. It was established using brief duration stimuli (< 40 msec) that the IR depended on mechanical events associated with the onset of stimulation, whereas stimuli greater than 40 msec in duration were required to evoke the ER.6. For constant expiratory flow rate and a constant load, the ER of expiratory intercostal muscles increased as lung volume decreased within the limits set by maximal activation of the motoneurone pool as residual volume was approached.7. The ER to a constant load increased directly with the expiratory flow rate at which the load applied, also within limits set by maximal activation of the motoneurone pool.8. For a given load, the ER during phonation was greater than that occurring at a similar expiratory flow rate without phonation when the resistance of the phonating larynx was mimicked by an external airway resistance.9. It is argued that the IR is due to autogenetic inhibition arising from tendon organs and that the ER is due to autogenetic excitation arising from intercostal muscle spindles.10. The initial dominance of inhibition in this dual proprioceptive reflex control was not predicted by the servo theory. It is proposed that the reflex pathways subserving autogenetic inhibition are under a centrifugal control which determines in relation to previous experience (learning) the conditions under which autogenetic facilitation is allowed.

Airway Resistance↗

Medullary activation of intercostal fusimotor and alpha motoneurones.

1. Studies have been made of the anatomical localization in the brain stem of the sites at which tetanic stimulation evoke inspiratory and expiratory apneusis.2. The inspiratory responses arise from a relatively circumscribed region within the medulla corresponding to the nucleus reticularis giganto-cellularis and ventralis which give rise to the medullary contingent of the long reticulo-spinal tracts. Expiratory responses were obtained dorsal and lateral to this area, but not localized to any cyto-architectonically distinct region of the reticular formation.3. During the apneustic responses there was co-activation of the intercostal alpha and fusimotor neurones with reciprocal inhibition of the antagonistic motoneurones. The threshold for activation of the fusimotor neurones was usually lower than for the alpha motoneurones.4. Results with brief tetanic stimulation suggest that the long reticulospinal tracts are responsible for the apneustic responses and that the effects are mediated at segmental level over an interneuronal pathway.5. The response of the intercostal motoneurones during the apneustic responses is shown to be dependent on the integrity of the dorsal spinal roots.

Animals↗