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T A Sears

Publications and source records attributed to T A Sears.

At least 19 recordsLinked to original sources
PubMed1995

Spontaneous synchronized neural activity in decerebrate gallamine-paralysed cats.

In decerebrate cats paralysed with gallamine, over a period of several days there develops a remarkable synchronization of discharge in widely different motor nerves throughout the body, including intercostal nerves and limb nerves. These discharges are also in synchrony with slow waves approximately 100 ms in duration in the inferior olive. The slow waves and discharges are at first irregular and only weakly synchronized, but become increasingly strongly synchronized and by about the fourth day exhibit a strong 6-8 Hz rhythm. The degree of synchronization is greater the lower the end-tidal CO2 concentration. Transection of the spinal cord at a high cervical level breaks the synchrony and may abolish the discharge in the nerves, but the slow waves in the inferior olive continue rhythmically. It was shown, however, that gallamine injected subdurally at cervical vertebra 7 or lumbar vertebra 7 has a direct excitatory action on the spinal cord. Slow waves in the inferior olive are elicited by gallamine in the decerebrate, spinalized and decerebellectomized cat, and therefore must originate in the brainstem. Gallamine is known to act directly on olivary neurons and the slow waves may originate in the inferior olive, but further experiments are needed to determine what other structures it affects. The condition of the cat a few days after decerebration and paralysis resembles the clinical condition of reticular reflex myoclonus and it is suggested that the genesis of the myoclonus may be similar in the two conditions.

Animals↗
PubMed1993

Ultrastructure of gamma-motoneurons after temporary or permanent interruption of peripheral target contact.

The paradigm of nerve crush, vs. nerve transection and ligation, was used to examine the effects of temporary or permanent interruption of peripheral target contact on the ultrastructure of cat thoracic gamma-motoneurons. The normal, highly ordered ultrastructure of Nissl bodies was lost 8 days after axotomy. Nissl bodies remained disorganised up to 305 days after nerve transection and ligation. In contrast, normal ultrastructural orderliness was restored for many of the Nissl bodies of gamma-motoneurons 64 days following nerve crush. A decrease in the area of the Golgi apparatus was found 64 days following both nerve crush and nerve transection with ligation. Other organelles were unaltered.

Animals↗
PubMed1993

Contralateral projections of thoracic respiratory interneurones in the cat.

1. Retrograde neuronal transport following small iontophoretic injections of horseradish peroxidase was used to investigate the location of neurones projecting to the thoracic ventral horn of the cat. 2. A concentration of labelled neurones was seen in the contralateral medial ventral horn at the immediately opposite rostrocaudal position. 3. The participation of respiratory interneurones in the projection was investigated by means of spike-triggered averaging, as follows. 4. Spike trains of single interneurones whose firing patterns were related to the central respiratory cycle were recorded extracellularly in the thoracic ventral horn of anaesthetized, paralysed cats. Firing patterns were defined by the construction of cycle-triggered histograms. 5. Spike-triggered averaging of the signal from an extracellular tungsten microelectrode in the opposite ventral horn was performed to test for the presence of axonal, terminal or focal synaptic potentials. 6. At least one of these types of potential was found for 34/55 units. Terminal potentials were found for thirty-one units, accompanied by focal synaptic potentials for twenty-seven units. Potentials were found for units with all types of firing patterns. Units whose activity elicited these potentials were generally located in the medial half of the ventral horn. 7. We conclude that at least 60% of the respiratory interneurones project to the immediately opposite ventral horn.

Action Potentials↗
PubMed1993

Functional identities of thoracic respiratory interneurones in the cat.

1. Spike-triggered averaging was used to reveal focal synaptic potentials (FSPs) in the thoracic ventral horn resulting from impulses in individual respiratory interneurones situated in the contralateral ventral horn of the same segment (T6 or T7) in anaesthetized paralysed cats. 2. FSPs were of two types, negative-going or positive-going, and were of the same sign at each of several sites for each unit. These two types were interpreted as indicating excitatory or inhibitory actions respectively. 3. The positive-going FSPs were almost all the result of activity in the most strongly modulated, phasic respiratory interneurones, whereas most of the negative-going ones were derived from neurones with a continuous tonic component in their firing patterns. 4. Positive-going FSPs (particularly those from inspiratory neurones) were generally found at more ventral sites in the ventral horn than negative-going ones. 5. It is suggested that an important role for the phasically active interneurones is to provide phasic inhibition, which is combined with largely tonic excitation to produce strong respiratory modulation in the activity of other neurones in the thoracic spinal cord, particularly in motoneurones. However, some groups of respiratory interneurones, such as a group of tonic inspiratory ones which are located more dorsally than the phasic inspiratory ones, may not receive such phasic inhibition.

Action Potentials↗
PubMed1991

Focal blockade of single unit synaptic transmission by iontophoresis of antagonists.

We have assessed the use of iontophoresis for investigating the pharmacology of synaptic transmission from individual presynaptic neurones in-vivo, by modifying extracellular focal synaptic potentials (FSPs) recorded by spike-triggered averaging. FSPs from two types of excitatory neurone (muscle spindle primary afferents and expiratory bulbospinal neurones) and from one inhibitory interneurone were studied in the thoracic ventral horn of anaesthetized cats. The antagonist of excitatory amino acids at non-NMDA receptors, DNQX, blocked the FSPs from the first two, as did bicuculline for the third. Thus the FSPs were generated by excitatory amino acids acting via non-NMDA receptors and GABA, respectively. The postsynaptic neurones were probably motoneurones. Merits and limitations of the method are discussed.

Animals↗
PubMed1991

The effects of opiates on the respiratory activity of thoracic motoneurones in the anaesthetized and decerebrate rabbit.

1. Efferent discharges were recorded from inspiratory and expiratory intercostal nerve filaments (T2-T10) in artificially ventilated, anaesthetized or decerebrate rabbits with or without vagotomy. 2. Hypocapnic apnoea was used to study the fractional end-tidal CO2 (FET,CO2)-dependent tonic discharges of the expiratory motoneurones, the FET,CO2 threshold for rhythm generation and the FET,CO2 response curve of both inspiratory and expiratory burst activity. 3. Incremental doses of morphine (e.g. 1 mg kg-1 I.V.) produced slowing of the respiratory rhythm due to prolongation of the expiratory duration and an elevation of the FET,CO2 threshold for rhythm generation. Eventually apnoea supervened with associated tonic firing of the expiratory motoneurones. At the elevated levels of FET,CO2 bursts of inspiratory activity, with concomitant phasic inhibition of the tonic expiratory activity, could occur either spontaneously or following sensory stimulation. The peak integrated activities of these bursts were closely similar to the values obtained for corresponding levels of FET,CO2 before the administration of morphine. 4. Tonic expiratory activity responded to increased levels of FET,CO2, as it had during hypocapnic apnoea prior to morphine, by an increased discharge frequency of single units or recruitment of new units. 5. All of these effects of morphine were immediately reversed by naloxone (100 micrograms kg-1). 6. Naloxone (greater than 100 micrograms kg-1), without pre-treatment with morphine, led to an increase in respiratory frequency due to a shortening of the expiratory duration and a dose-dependent reduction in the FET,CO2 threshold for rhythm generation. There was little alteration either in the inspiratory response to FET,CO2 during rhythm or in the FET,CO2 response of the expiratory output whether expressed as tonic activity during hypocapnic apnoea or phasic activity following the onset of rhythm. 7. Thus opiates act upon the mechanisms of rhythm generation without depressing the FET,CO2 drive as expressed either as phasic or tonic activation of the motoneurones.

Animals↗
PubMed1990

A threshold effect of the major isoforms of NCAM on neurite outgrowth.

Interactions between recognition molecules on the surface of neuronal growth cones and guidance cues present in the local cellular environment are thought to account for the growth of neurites in the highly stereospecific manner that contributes to correct target cell innervation. In vitro assays have been used to identify candidate molecular components of this system, either directly by demonstrating their ability to promote neurite outgrowth, or indirectly by the ability of specific antibodies to inhibit neurite outgrowth. The role of the neural cell adhesion molecule (NCAM) in pathway finding is not fully understood. Some immunological studies support a positive role; others do not, and it has been reported that purified NCAM does not support neurite outgrowth. We have previously shown that an arbitrary biochemical index of neurite outgrowth, the relative level of immunoreactive neurofilament protein, is increased when human and rat dorsal root ganglion neurons are cultured on monolayers of cells expressing transfected human NCAM. But, the complexity of growth precluded a simple morphological analysis and we did not determine the 'dose-response' relationship between NCAM expression and neuronal response. Here, we report on the morphology of rat cerebellar neurons cultured on monolayers of 3T3 cells transfected with complementary DNAs encoding all of the main NCAM isoforms found in cells such as astrocytes, Schwann cells and skeletal muscle. The data indicate that both transmembrane and glycosyl-phosphatidylinositol linked NCAM isoforms are potent substrates for neurite extension. A critical threshold value of NCAM expression is required for increased neurite outgrowth. Above this threshold, small increases in NCAM induce substantial increases in neurite outgrowth.

Animals↗
PubMed1989

Organelle changes in cat thoracic alpha- and gamma-motoneurons following axotomy.

Horseradish peroxidase was used as a retrograde marker to identify the cell bodies of cat thoracic alpha- and gamma-motoneurons 8 days following axotomy. A quantitative ultrastructural comparison revealed changes in Nissl bodies, the Golgi apparatus, mitochondria and lysosomes for axotomised alpha-motoneurons, while axotomised gamma-motoneurons only showed changes in Nissl bodies and nuclear pores.

Animals↗
PubMed1988

Respiratory interneurones in the thoracic spinal cord of the cat.

1. The discharges of spontaneously firing neurones, whose activity was modulated in phase with the central respiratory cycle, were recorded in the thoracic ventral horn (T3-T9) of anaesthetized, paralysed cats. 2. Out of 310 neurones, forty-six were positively identified as motoneurones by antidromic activation or spike-triggered averaging, fifty-four were positively identified as interneurones by antidromic activation from other spinal cord segments and ninety were indirectly identified as interneurones by virtue of their positions or firing rates as compared to the motoneurones. 3. Units were classified as inspiratory (64%), expiratory (25%) or post-inspiratory (7%) according to the times of their maximum firing rates. The remaining 4% consisted of units whose discharges were either strongly locked to the respiratory pump cycle or did not fit into the other categories. All but one of the motoneurones were classified as inspiratory or expiratory. 4. Inspiratory and expiratory units were further classified as early, late or tonic according to the starting times of their discharges in the respiratory cycle. The interneurones (both positively and indirectly identified) included more of the early and tonic categories and more fast-firing units than did the motoneurones in both the inspiratory and expiratory groups. 5. The locations of the motoneurones corresponded to the known positions of the intercostal and interchondral motor nuclei, including clear segregation of inspiratory and expiratory populations. The locations of neither the interneurones nor the unidentified units were segregated according to their firing patterns. These neurones were concentrated in the medial half of the ventral horn and were found generally more dorsally than the positions of the motoneurones, though their positions overlapped considerably with this group. 6. The axons of the positively identified interneurones were identified from one to five segments caudally and mostly contralaterally, but were not traced to their terminations. Some axons were located by microstimulation and found to run in the ventral or ventromedial white matter. Conduction velocities covered a wide range, 8 to around 100 m/s, mean 53 m/s. 7. Preliminary calculations indicate that there may be almost 10 times more respiratory thoracic interneurones as respiratory bulbospinal neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1988

The development of voltage-dependent ionic conductances in murine spinal cord neurones in culture.

The development of voltage-dependent ionic conductances of foetal mouse spinal cord neurones was examined using the whole-cell patch-clamp technique on neurones cultured from embryos aged 10-12 days (E10-E12) which were studied between the first day in vitro (V1) to V10. A delayed rectifier potassium conductance (Ik) and a leak conductance were observed in neurones of E10, V1, E11, V1, and E12, V1 as well as in neurones cultured for longer periods. A rapidly activating and inactivating potassium conductance (IA) was seen in neurones from E11. V2 and E12, V1 and at longer times in vitro. A tetrodotoxin (TTX) sensitive sodium-dependent inward current was observed in neurones of E11 and E12 from V1 onwards. Calcium-dependent conductances were not detectable in these neurones unless the external calcium concentration was raised 10-to 20-fold and potassium conductances were blocked. Under these conditions calcium currents could be observed as early as E11. V3 and E12, V2 and at subsequent times in vitro. The pattern of development of voltage-dependent ionic conductances in murine spinal neurones is such that initially leak and potassium currents are present followed by sodium current and subsequently calcium current.

4-Aminopyridine↗
PubMed1988

Ultrastructure of interneurons within motor nuclei of the thoracic region of the spinal cord of the adult cat.

Alpha (greater than 40 microns) and gamma (less than 30 microns) motoneurons in inspiratory motor nuclei of the thoracic spinal cord of the adult cat were labelled retrogradely by the intramuscular injection of HRP. Small (less than 30 microns) unlabelled neurons within 200-300 microns of labelled motoneurons were analysed qualitatively and quantitatively with both the light and electron microscope. Most of these small unlabelled neurons had inconspicuous nucleoli, wrinkled nuclear membranes, low numbers of nuclear pores, and Nissl bodies which were either small or had the form of an amorphous perinuclear band. Such Nissl bodies were composed primarily of aggregates of polyribosomes within which short fragments of granular endoplasmic reticulum were distributed. Alpha and gamma motoneurons in contrast had prominent nucleoli, smooth-contoured nuclei, more nuclear pores and large, discrete Nissl bodies. Such Nissl bodies were composed primarily of several lamellae of granular endoplasmic reticulum with linear arrays of polyribosomes arranged between individual cisternae. Alpha motoneurons had most synaptic terminals on their cell bodies, gamma motoneurons had least and small unlabelled neurons had intermediate values. Synaptic terminals of the S-, F- T- and C-type were observed on alpha motoneurons, whereas only S- and F-types were observed on gamma motoneurons and small unlabelled neurons. Since they were unlabelled and differed morphologically from both alpha and gamma motoneurons, but were similar to small interneurons described elsewhere in the spinal cord and brain, it is suggested that the small unlabelled neurons located in the external intercostal and levator costae motor pools are interneurons. The functional significance of some of the morphological features which distinguish interneurons from motoneurons is discussed.

Animals↗
PubMed1987

Identification and electrophysiological investigations of embryonic mammalian motoneurones in culture.

The retrograde transport of fluorochromes from muscle was used to label embryonic rat motoneurones in vivo. The fluorescent motoneurones were subsequently detected in cultures of dissociated spinal cord neurones using an image-intensification video camera, the images from which allowed identification of the motoneurones under phase-contrast microscopy. Such motoneurones were mostly phase dark, often with a multipolar appearance and were detectable for up to 4 days in culture. Whole-cell patch-clamp recordings from these motoneurones demonstrated mean input resistances of 635 M omega and resting membrane potentials of -65 mV; action potentials could be evoked and, under voltage-clamp, inward and outward currents were present.

Animals↗
PubMed1987

Spatio-temporal characterization of intercostal activity during breathing in the cat.

It is envisaged that the motor control of the intercostal musculature--an assembly of mobile structures--can be characterized in terms of a conceptual spatially continuous control function, that underlies the discretely distributed muscular activity and reflects an inferred global dynamic control of the thoracic cage during breathing. The global control function is estimated by the spatio-temporal pattern obtained by averaging in time and space and interpolation of multichannel simultaneous intercostal EMG recording in the anaesthetized cat. Different examples of the experimental preparation in the presence of stimuli of different kinds are analysed. The resultant signal patterns are found to be self-consistent and capable of exhibiting systematically differing features in systematically differing experimental conditions, thus supporting the validity of the analysis and the choice of the estimator. It is concluded that a more detailed analysis of the requirements of this approach is then warranted. Such requirements are discussed, and, specifically, results that bear on the adequacy of spatial sampling rate are presented. It is suggested that such methods offer a promising approach in the study of motor control strategies of the respiratory apparatus.

Algorithms↗
PubMed1987

Intercostal muscles and purring in the cat: the influence of afferent inputs.

Feline purring has previously been reported as originating in a central oscillator, independent of afferent inputs, and also as not involving expiratory muscles. Here we show, via electromyographic recordings from intercostal muscles, quantified by cross-correlation, that expiratory muscles can be involved and that even if the oscillator is central, reflex components nevertheless play a considerable part in the production of the periodic pattern of muscle activation seen during purring.

Animals↗
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↗