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T A Sears

Publications and source records attributed to T A Sears.

At least 37 records · Page 2Linked to original sources
PubMed1987

Structural changes in intercostal motoneurones following axotomy.

Motoneurone disease (MND or amyotrophic lateral sclerosis) is a paralysing disease of unknown cause involving progressive, widespread muscle atrophy due to degeneration of spinal and other motoneurones and an accompanying loss of Betz cells in the motor cortex. A current hypothesis attributes the disease to the loss of a muscle-derived neurotrophic factor acting in concert with the normal age-related deterioration and loss of motoneurones. The roots of this hypothesis are traced through research based mainly on the developing neuromuscular system, and in particular on the age-related processes of natural motoneurone death during embryogenesis: the neonatal reduction of polyneuronal innervation and the age-dependent variations in motor nerve terminal sprouting in response to partial denervation. A consideration of the disease process itself in association with the review of earlier work provide the background for the present work which reexamines ultrastructurally the chromatolytic and later responses to axotomy and the muscle-dependent factors responsible for the reformation of the Nissl bodies.

Animals↗
PubMed1986

Involvement of the dorsal root ganglion in acute experimental allergic encephalomyelitis in the Lewis rat. A histological and electrophysiological study.

Histological and electrophysiological studies were performed in Lewis rats with acute experimental allergic encephalomyelitis (EAE) in order to determine the extent of dorsal root ganglion (DRG) involvement. Histological studies showed inflammation and demyelination in both the central nervous system (CNS) and peripheral nervous system (PNS). The DRG was the most affected region of the PNS and its involvement increased caudally. Nerve conduction abnormalities were demonstrated in the regions of the lumbar, sacral or coccygeal DRGs in some of the rats with EAE. However, the overall DRG involvement was much less severe, both histologically and functionally, than what we recently found in rabbits with EAE. Conduction through the lumbar dorsal root entry zone was normal. We conclude that lesions of the afferent pathway to the spinal cord do not contribute significantly to the disturbances of hindlimb motor function in Lewis rats with EAE.

Animals↗
PubMed1986

Effects of sagittal medullary section on high-frequency oscillation in rabbit phrenic neurogram.

Six rabbits were anaesthetized with chloralose and urethane and were subjected to sagittal section of the medulla in the region of obex to a few mm rostral to obex. The sections had an initial rostro-caudal length of 4 mm and were gradually extended until the respiratory rhythms on the two sides of the animal, as seen in phrenic discharges, became dissociated. High-frequency oscillation in the phrenic discharge, assessed either by visual inspection of the neurogram or by cross-correlation between the discharges in the two phrenic roots on one side, was abolished by sections for which the intensity of the phrenic discharge was hardly affected. These sections were smaller than those required to dissociate the respiratory rhythms on the two sides of the animal.

Animals↗
PubMed1985

Target dependence of Nissl body ultrastructure in cat thoracic motoneurones.

The effects on Nissl body (NB) ultrastructure of muscle reinnervation or neuroma formation were determined in cytochemically identified cat thoracic motoneurones subjected to axotomy by either nerve crush or nerve section with proximal ligation. Normal NB ultrastructure comprised highly ordered lamellae of rough endoplasmic reticulum (RER) with associated linear arrays of unbound polyribosomes. This ultrastructural orderliness was lost following axotomy, with or without light microscopic chromatolysis. While NBs were seen in the light microscope at late stages following both nerve crush or ligation, normal NB ultrastructure was only observed following nerve crush. An inductive effect of the periphery on NB ultrastructure is proposed and the implication of NB ultrastructure discussed in relation to protein synthesis.

Animals↗
PubMed1985

The respiratory activity of human levator costae muscles and its modification by posture.

The activation of the levator costae, a set of axial muscles inserted between each rib and the vertebra immediately rostral, has been studied electromyographically in a human subject, standing upright, with head erect ('neutral' posture). Caudal levator costae muscles (T9, and T10) are active during eupnoea. Periodic activity in phase with inspiration occurs in admixture with different levels of tonic activity that is strongly influenced by posture. Postural changes and various voluntary respiratory manoeuvres which should lengthen or shorten the levator costae muscles increase and decrease, respectively, their activity in the 'neutral' posture. The tonic activity was most readily enhanced by contralateral flexion of the spine, and this could bring to threshold phasic activity not otherwise present. Conversely, ipsilateral flexion could abolish both phasic and tonic components. Active expiratory efforts and static voluntary relaxation of the respiratory muscles could diminish or abolish levator costae activity. Paradoxically, chest-directed inspiratory efforts maintained at elevated lung volume with open glottis could also diminish or abolish levator costae activity. We attribute this to shortening of the levator costae muscles and unloading of their muscle spindles by the elevation of the ribs due to the action of the external intercostal and parasternal muscles. The results are discussed in relation to the mechanical coupling between the diaphragm and the lower rib cage; emphasis is given to the possible independent motions of the lower two or three ribs and the abductor action of their corresponding levator costae muscles, based on anatomico-physiological considerations.

Chin↗
PubMed1985

The detection of monosynaptic connexions from inspiratory bulbospinal neurones to inspiratory motoneurones in the cat.

Simultaneous recordings were made of the discharges of inspiratory bulbospinal neurones and phrenic or external intercostal alpha-motoneurones in the anaesthetized cat. The connexions between these neurones were studied by the construction of cross-correlation histograms from their discharges. Peaks observed in the cross-correlation histograms were divided into three groups on the basis of their time courses: narrow, medium-width and high-frequency oscillations (h.f.o.). Narrow peaks were defined as having half-widths less than 1.1 ms and medium-width peaks as having half-widths greater than this, while h.f.o. was characterized by periodic waves in the range 60-120 Hz. H.f.o. peaks were interpreted as being derived from the well known periodic synchronization of medullary inspiratory neurones in this frequency range. The time courses and latencies of the medium-width peaks could be quantitatively explained by a simple model representing excitation of the motoneurones by bulbospinal neurones whose discharges showed synchronization within +/- 1 ms of the reference spike, together with temporal dispersion in bulbospinal axons having a distribution of conduction velocities given by the measurements of this study. Such an explanation was essential for some of the medium-width peaks, whose latencies were short compared to the conduction times to the spinal cord for their own axons, but for other medium-width peaks oligosynaptic excitation of the motoneurones from the identified bulbospinal neurones was another possible explanation. The narrow peaks were of appropriate durations for monosynaptic connexions and were all at appropriate latencies (0.6-2.4 ms after the calculated arrival time of the bulbospinal impulse in the segment concerned). It is concluded from the observations of narrow peaks that monosynaptic excitation exists between inspiratory bulbospinal neurones and both phrenic and external intercostal motoneurones. However, because of the existence of presynaptic synchronization, as shown by the presence of the medium-width peaks, such a conclusion is predicated upon being able to discriminate against such an effect. The model showed that this restriction applies just as much to the measurements of excitatory post-synaptic potentials (e.p.s.p.s) by spike-triggered averaging as it does to cross-correlation measurements. We suggest that the discrimination against presynaptic synchronization here was possible only because the long conduction distance created temporal dispersion in the synchronized presynaptic impulses.

Action Potentials↗
PubMed1985

The distribution of monosynaptic connexions from inspiratory bulbospinal neurones to inspiratory motoneurones in the cat.

Monosynaptic connexions were sought between bulbospinal inspiratory neurones and inspiratory motoneurones of the C5 phrenic nerve or the intercostal nerves of up to six segments in the anaesthetized cat; they were identified by the presence of narrow peaks in cross-correlation histograms constructed from the spontaneous discharges of these neurones. About half of the bulbospinal neurones tested with the phrenic gave a monosynaptic connexion, as did just under half of those tested with the intercostal nerves. Some neurones gave connexions to both. For pairs of bulbospinal neurones and intercostal nerves, connexions were seen in 50 out of 295 instances (17%). No evidence was found of systematic patterns of connexions to different segments. Some neurones gave connexions to adjacent segments, others up to five segments apart. Bulbospinal neurones were not equipotent at giving connexions to the intercostal motoneurones. If a neurone gave a connexion to one segment, it was more likely to give connexion to another segment than chance would predict. The neurones with strong connexions were concentrated rostral to obex in the ventral respiratory group; neurones in both the caudal part of the ventral group and in the dorsal group gave weaker connexions. Regional variation within the medulla in the proportions of neurones giving connexions to the phrenic motoneurones was not seen, in particular neurones of the dorsal group (eight out of sixteen) and the ventral group (five out of eleven) were equipotent. When the strength of the connexions was assessed by k, the ratio of the peak count in the cross-correlation histogram to the base-line count, the mean strength was similar for the peaks seen for the phrenic (k = 1.113) and the intercostal (k = 1.114) motoneurones. However, because, on a segment-by-segment basis, fewer connexions were seen for the intercostals, the over-all mean value of k (absence of a narrow peak taken as k = 1.0) was stronger for the phrenic (k = 1.055) than for the intercostals (k = 1.019). For the phrenic, the apparent strength of connexion (assessed by k) was considerably stronger for the motoneurones giving large spikes than for those giving small ones. The same result was probably also true for the intercostals. With several assumptions, the total depolarization during inspiration derived monosynaptically in phrenic or intercostal motoneurones was calculated and found to be low, about 1 mV for the intercostals and 3-4 mV for the phrenic.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Vulnerability of the dorsal root ganglion in experimental allergic encephalomyelitis.

The dorsal (posterior) root ganglion is a relatively neglected part of the nervous system from the clinical point of view. In recent studies on the pathophysiology of experimental allergic encephalomyelitis (EAE), the main animal model of multiple sclerosis, the DRG of the rabbit was shown to be the site of extensive inflammation and demyelination and of focal conduction block in a high proportion of the large diameter afferents. The resulting severe functional peripheral deafferentation accounts for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. The vulnerability of the DRG is due to a deficient blood-nerve barrier and possibly also to a susceptibility of the branch point of the ganglion neurone to demyelination-induced conduction block. These and other studies in experimental animals suggest that in man the DRG may be a preferential (but neglected) site of focal structural and functional abnormalities in inflammatory and also other neurological diseases.

Action Potentials↗
PubMed1984

Electrical activity of mouse motor nerve terminals.

Focal extracellular recording was made from presynaptic motor nerve terminals made visible directly in in vitro preparations of mouse intercostalis intimi muscles. The demonstration of a net inward current distally in these terminals at sites of transmitter release allow the conclusion that the mammalian terminal is electrically excitable, contrary to a recent claim that it is not.

Animals↗
PubMed1984

The pathophysiology of acute experimental allergic encephalomyelitis in the rabbit.

Clinical, histological and electrophysiological studies were performed on rabbits with acute experimental allergic encephalomyelitis (EAE). The clinical features were similar to those previously described, with the notable exception of the new findings of areflexia, respiratory slowing and hypothermia. The histological findings were also similar to those previously reported, with inflammatory demyelinating lesions both in the central and peripheral nervous system, especially the dorsal root ganglia. Electrophysiological studies performed one to nine days after the onset of neurological signs demonstrated conduction block in a high proportion of the large diameter afferents in the lumbosacral and thoracic dorsal root ganglia. Single fibre studies with spike-triggered averaging confirmed the conduction block in the dorsal root ganglia. That the conduction block was due to demyelination was indicated by slowing of conduction in large diameter fibres, normal conduction in unmyelinated fibres and the specific effects of temperature and of the potassium channel blocking agent, 4-aminopyridine. These conduction abnormalities in the peripheral nervous system, focused on the dorsal root ganglia, account for the postural disturbance, hypotonia, ataxia and areflexia in rabbits with EAE. Such conduction block is likely to mask the expression of any lesions of the central nervous system that alone could produce similar signs. The implications of these findings for the human demyelinating diseases are discussed.

Afferent Pathways↗
PubMed1984

Restoration of function in external intercostal motoneurones of the cat following partial central deafferentation.

The activity of external intercostal motoneurones in the cat was studied under anaesthesia and paralysis before and after partial central deafferentation caused by single or double ipsilateral hemisections of the thoracic spinal cord. The normal efferent inspiratory discharges recorded from external intercostal nerve filaments caudal to the upper lesion were greatly reduced acutely, but activity of approximately normal intensity and phase at eupneoic levels of CO2 was restored within a few days and remained at similar levels for up to two years. The patterns of the restored activity were abnormal, with more discharges of alpha-motoneutrones during expiration than normal and a stronger modulation of the discharges by the respiratory pump than normal. A common abnormal component of the restored activity was a tonic discharge in hypocapnic apnoea, often modulated by the respiratory pump. This activity was never seen in normal animals or in those with acute lesions under similar conditions of anaesthesia. Synchronization of the discharges of alpha-motoneurones caudal to the upper lesion was studied by constructing cross-correlation histograms between paired groups of motoneurones, each group being represented by the discharges in one filament. Synchronization was stronger than normal, usually extending over a time course of +/- 20 to +/- 50 ms (broad-peak synchronization). This synchronization was particularly strong for the discharges in hypocapnic apnoea. We conclude that the restored activity was derived in large part from abnormal tonic (non-respiratory-phased) inputs, partly proprioceptive in origin, probably involving spinal cord interneurones with abnormally synchronized discharges. This conclusion is supported by intracellular measurements including respiratory drive potentials, synaptic noise and average common excitation potentials.

Action Potentials↗
PubMed1983

Trophism between C-type axon terminals and thoracic motoneurones in the cat.

1. Quantitative ultrastructural examinations of axon terminals synapsing with normal alpha-motoneurones in segment T9 of cat spinal cord provided estimates of their numbers, sizes and synaptic structure. One synapse, the C type, derived from short-axon propriospinal segmental interneurones, was studied in detail.2. The numbers, sizes and post-synaptic structure of normal C-type synapses at T9 were compared with similar estimates from material provided by cats subjected to partial central deafferentation by double spinal hemisection at T5 and T10 between 7 days and 2 years previously.3. The proportion of C-type synapses present progessively increased from 1% in normal cats to 8.8% 200 days following hemisection, and had still attained a level of 3.1% by 2 years; these increases imply that the absolute number of C-type synapses underwent increase.4. Mean sizes of C-type synapses increased from 4.0 mum (normal) to 5.8 mum (200 days) and retained their enlarged sizes up to 2 years (5.9 mum). Furthermore, while 84% of C-type synapses were under 6 mum in length in normal motoneurones, 48% were over 6 mum long 200 days post-operatively.5. The unique post-synaptic structure of C-type synapses also proliferated following partial central deafferentation of the motoneurones. The elongated cistern, increased numbers and individual lengths of lamellae of the associated underlying rough endoplasmic reticulum indicated a trophic interaction between the presynaptic C terminal and its post-synaptic motoneurone.6. Counts of ribosomes ;bound' to lamellae of the subsynaptic rough endoplasmic reticulum, and of the lamellae-associated polyribosomes interposed between individual lamellae for normal and 200 day post-operative C-type synapses indicated an over-all post-operative increase in capacity for local subsynaptic protein synthesis topographically directed towards this type of axon terminal.7. The observed greater increase in frequency of ribosomes ;bound' to the rough endoplasmic reticulum, together with an over-all proliferation of this structure, specificially indicated an increased capacity for synthesis of protein for utilization in sites remote from those of synthesis (e.g. a trans-synaptic passage of protein).8. A hypothesis is advanced on the basis of the above results relating both pre- and post-synaptic changes in structure to an increased functional activation of the segmental short-axon propriospinal interneurones forming the C-type synapses, as a compensatory response to partial central deafferentation of spinal motoneurones.

Afferent Pathways↗
PubMed1983

The spatial distribution of excitability and membrane current in normal and demyelinated mammalian nerve fibres.

Thresholds to electrical stimulation have been recorded, concurrently with the membrane currents of conducted impulses, at many positions along undissected single fibres in rat spinal roots. In normal myelinated fibres, distinct threshold minima invariably coincided with sites of inward current generation, and were therefore identified as nodes of Ranvier. Between nodes, the thresholds rose by an order of magnitude. At normal nodes, the charge thresholds were linearly related to stimulus duration, as predicted by computer simulations of a model myelinated fibre (Bostock, 1983). The strength-duration time constants averaged 64.9 +/- 8.3 microseconds (mean +/- S.D.) at 37 degrees C, and had a Q10 of 1/1.39. They were relatively insensitive to changes in inter-electrode distance, or to partial anaesthetization with tetrodotoxin. In fibres treated with diphtheria toxin 6-8 days previously, to induce paranodal or segmental demyelination, threshold minima were found both at nodes and in internodal regions generating inward membrane current. In these fibres strength-duration curves were of the same general form as at normal nodes, but with strength-duration time constants increased at widened nodes (up to 350 microseconds) and at excitable internodes (600-725 microseconds). Comparison with the computer model indicated that these changes were most likely due to exposure of axon membrane with a time constant much longer than that of the normal nodal membrane. In none of the demyelinated fibres examined have we found any evidence of hyperexcitability.

Animals↗
PubMed1983

Central and proprioceptive influences on the activity of levator costae motoneurones in the cat.

The role of central respiratory drive, muscle spindles and tendon organs in producing respiratory movements has been studied in the cat by recording from motoneurones supplying a set of small axial muscles inserted between each rib and the vertebra immediately rostral, the levatores costae. The levator costae muscles are active during normal inspiration but activity is progressively stronger in the muscles located in more caudal thoracic segments. Intracellular recordings from levator costae motoneurons show a characteristic central respiratory drive potential (c.r.d.p.), comprising phases of depolarization during inspiration alternating with expiratory phased hyperpolarization due to post-synaptic inhibition. Loading or unloading the levator costae muscles increases and decreases, respectively, their normal inspiratory activity. Electrophysiological and histological analysis of levator costae afferents reveals that each muscle contains three to five spindles and two to three tendon organs. By dissecting the levator costae nerve, afferent discharges from muscle spindle primary and secondary endings and those from tendon organs were recorded 'in continuity' and used to trigger an averager for analysing the synaptic potentials they evoke in levator costae motoneurones. Monosynaptic excitation and oligosynaptic inhibition originate from spindle (primary and secondary endings) and from tendon organ afferents respectively. Peculiarly a monosynaptic excitation has been evoked from a tendon organ. The action of the levator costae muscle on the respiratory movements of the ribs in the different thoracic spaces was analysed in relation to their anatomical properties and to the activity of the other respiratory muscles. The levator costae muscles, because of their relatively small size and well-defined population of proprioceptors, appear to provide a favourable preparation for studying the integrative action of the motoneurone.

Animals↗
PubMed1982

Excitatory post-synaptic potentials from single muscle spindle afferents in external intercostal motoneurones of the cat.

1. The discharges of muscle spindle afferents from the external intercostal muscles of anaesthetized, paralysed cats were recorded from dorsal roots in continuity. The dynamic responses, regularities of firing and conduction velocities of the afferents were measured and used to characterize the afferents as primary-like or secondary-like. 2. The synchronization of afferent discharges was investigated by the construction of cross-correlation histograms from the simultaneously recorded discharges of pairs of afferents. The discharges of primary-like afferents with high dynamic responses were found to be synchronized within a few msec. The cardiac pulse was a strong contributary factor in this synchronization. 3. Intracellular recordings were made from external intercostal motoneurones, and spike-triggered averaging was used to reveal unitary e.p.s.p.s evoked by muscle spindle afferents which were from the same spinal cord segment. Dorsal roots other than the rootlet containing the afferent were cut to prevent the synchronization of afferent discharges from affecting the averaged e.p.s.p.s. 4. For primary-like afferents the mean amplitude of the e.p.s.p.s was 171 microV and the mean connectivity (the proportion of motoneurones connected by one afferent) was between 42 and 48%. 5. The amplitudes and shapes of the e.p.s.p.s varied with the respiratory phase, usually being larger in inspiration than in expiration and sometimes also having a longer time course. In particular some e.p.s.p.s showed that components, only represent in inspiration, which were interpreted as indicating polysynaptic connexions gated by the respiratory cycle. 6. The results are discussed in comparison with the connexions of individual muscle spindle afferents from other muscles, with particular reference to the conduction velocities of the afferents.

Action Potentials↗
PubMed1982

The effects of single afferent impulses on the probability of firing of external intercostal motoneurones in the cat.

1. Recordings of afferent discharges from external intercostal muscle spindles were made from in-continuity dorsal roots of anaesthetized, paralysed cats and the afferents were characterized as described in the preceding paper (Kirkwood & Sears, 1982).2. The strengths and time courses of the raised probabilities of firing of external intercostal motoneurones evoked by the synaptic actions of impulses in the afferents were measured by constructing cross-correlation histograms from the discharges of the individual afferents and the discharges of the motoneurones, which were simultaneously recorded from the cut central ends of intercostal nerve filaments. Other dorsal roots, apart from the rootlet containing the afferent fibre, were cut to prevent afferent synchronization from affecting the results.3. Cross-correlation histograms involving single efferent discharges showed narrow peaks (mean half-width 0.99 msec) at monosynaptic latencies.4. This mean half-width is slightly longer than the mean rise-time of the e.p.s.p.s described in the preceding paper, but much shorter than the mean half-width of those e.p.s.p.s. These measurements, together with the shapes of individual histogram peaks thus confirm the prediction of Kirkwood & Sears (1978) that the shape of such a peak should be approximated by the time differential of the underlying e.p.s.p. plus the e.p.s.p. time course itself. Amplitudes of the peaks were also consistent with the predictions of Kirkwood & Sears (1978).5. The cross-correlation histograms involving multi-unit efferent discharges were entirely consistent with those involving single efferent discharges and were used to demonstrate the patterns of projections of individual afferents to different groups of intercostal motoneurones.6. Individual afferents excited alpha motoneurones of all spike sizes in the intercostal filament recordings but excitation of gamma motoneurones was not detected.7. Individual afferents excited motoneurones of the same segment and both adjacent segments, but no projection beyond these was detected.8. The amplitude of the multi-unit cross-correlation peak was taken as a measure of the over-all strength of the connexions to a given segment. When this amplitude was measured for motoneurones of the same segment as the afferent, for sixteen out of nineteen afferents there was a highly significant positive correlation with the conduction velocity of the afferent. The remaining three afferents gave a strength of connexion which appeared to be much stronger than would be expected from the rest of the population of afferents.9. The strength of connexion to adjacent segments was generally lower than to the same segment.

Action Potentials↗