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Biomedical subjects

A M Thomson

Publications and source records attributed to A M Thomson.

At least 109 records · Page 6Linked to original sources

The action of picrotoxin on the interspike interval in rat supraoptic neurones.

Effects of gamma-aminobutyric acid (GABA) antagonists on cells of the supraoptic nucleus have been investigated in isolated slices of rat hypothalamus. Bicuculline had no effect on firing patterns or the minimum interspike interval. Picrotoxin reduced the minimum interspike interval and caused long-lasting bursts of high-frequency spikes, an effect that persisted even when synaptic transmission was blocked. We suggest, that in this case, picrotoxin is not acting primarily as a GABA antagonist but as a blocker of chloride channels, thereby altering the cell properties that regulate the minimum interval.

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Selective blockade of an excitatory synapse in rat cerebral cortex by the sigma opiate cyclazocine: an intracellular, in vitro study.

In isolated slices of rat cortex, intracellularly recorded responses of pyramidal neurones to N-methylaspartate (NMA) and glutamate and responses to stimulation of the underlying white matter were compared and challenged with the sigma opiate cyclazocine. Cyclazocine blocked responses to iontophoretically applied NMA and one component of the postsynaptic response to stimulation, but left other postsynaptic events and responses to glutamate intact. These results are consistent with the view that sigma opiates act as selective NMA antagonists and block synaptic events mediated by NMA receptors.

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Regular firing patterns of suprachiasmatic neurons maintained in vitro.

Cells of the suprachiasmatic nucleus (SCN) recorded in vitro display a characteristic firing pattern. Unlike many other central neurons, they have the ability to fire at a constant low rate with fixed interspike interval. This regularity is most pronounced at firing rates above 3-5 spikes/s. Spontaneous firing below 3 spikes/s was less regular but became increasingly regular as the firing rate was increased. Similarly, regular discharges became irregular when the firing rate was reduced below 3-5 spikes/s. The mean spontaneous firing rate was 5.6 +/- 1.6, range less than 1 to 12 spikes/s and cells were resistant to attempts to increase their rate of firing beyond 15-20 spikes/s. Statistical analysis showed that the firing patterns of all the cells studied formed a single continuous population in terms of their interspike interval distributions, and that these distributions were a function of the firing rate. Addition of either of two commonly used anesthetics, urethane or sodium pentabarbitone, disrupted previously stable, regular activity.

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Correlations between the firing of supraoptic neurones in slices of rat brain.

These experiments were an attempt to study the possible interactions between cells of the supraoptic nucleus. In isolated brain slices pairs of supraoptic neurones were recorded simultaneously either with a single electrode or with two electrodes and cross-correlograms produced. Correlations were demonstrated in 22 of the 82 pairs studied and were found to be more common between closely neighbouring pairs of cells. Ten of the correlations indicated that the spikes of one cell followed spikes in the other cell. The correlations of another 10 pairs indicated that the cells were coactivated. In only 2 pairs was there a correlation indicative of an inhibitory connexion. That these correlations could result either from synaptic connexions within the nucleus, or from coactivation of cells from an extranuclear site is discussed.

Animals↗

Supraoptic neurons sustain high frequency firing when extracellular Ca2+ is replaced with other divalent cations in rat brain slices.

In slices of hypothalamus, maintained in vitro, the discharge of supraoptic neurons in standard artificial cerebrospinal fluid was compared with that produced when extracellular Ca2+ was replaced with Mg2+, Co2+ or Mn2+. Interspike interval histograms were constructed for periods before, during and after replacement of extracellular Ca2+. Of the 31 cells recorded in normal medium, 16 fired slowly and irregularly, 9 were phasic, 3 fired continuously at more than 3 spikes/s and 3 produced short, high frequency bursts of activity that were separated by slow irregular discharge. Interspike interval distributions were broad showing little preference for any one interval and intervals shorter than 30-50 ms were rare. The cell firing rate could be increased by the electrophoretic application of glutamate and under these conditions, the interval distributions became narrower as shorter intervals predominated. However, when cells discharged above 20 spikes/s, the spike amplitude declined rapidly and became indistinguishable from the noise. Replacement of extracellular Ca2+ with Mg2+, Co2+ or Mn2+ produced reversible changes in interspike interval distribution, although no consistent change in mean firing frequency was observed. Supraoptic neurons were now able to maintain relatively high frequency discharge (15-25 spikes/s) for longer periods; firing either continuously or periodically, and interspike intervals became grouped more closely at the shorter end of the normal distribution. However, no very short interspike were recorded. Less than 2% of all recorded intervals were shorter than 30 ms, even in cells exposed to test medium for 1-3 h and excited by application of glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)

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Slow, regular discharge in suprachiasmatic neurones is calcium dependent, in slices of rat brain.

The Ca2+ dependence of suprachiasmatic firing patterns was studied in isolated hypothalamic slices. Single neurones were first recorded in a standard artificial cerebrospinal fluid and then followed through a change to a medium in which the Ca2+ was replaced with Mg2+, Co2+ or Mn2+. These test media caused disruption of the normal, slow, regular firing patterns of suprachiasmatic neurones. Some interspike intervals were shorter and some longer than any recorded under normal conditions, for a given firing frequency. In the absence of Ca2+, these cells could not be driven to fire more regularly as they fired more rapidly during glutamate applications. In contrast, in the presence of Ca2+ more slowly and irregularly firing suprachiasmatic cells can be driven to fire regularly if their firing rate is increased. The effects of these test media were reversible. When Ca2+ was replaced with Ba2+, a bursting pattern of discharge resulted. Periods of high frequency discharge, possibly superimposed on Ba2+ spikes, alternated with periods of slow, regular firing or silence. It is concluded that Ca2+ is necessary for the maintenance of regular firing in suprachiasmatic neurones. The possibility that Ca2+ channels similar to those present in other slow, regularly firing central neurones, play an important role in suprachiasmatic activity, is discussed.

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The electrical properties of neurones of the rat suprachiasmatic nucleus recorded intracellularly in vitro.

Stable intracellular recordings were obtained from 22 suprachiasmatic neurones in isolated brain slices. These cells were characterized by resting potentials of about -60 mV, high input resistances, relatively short time constants and action potentials of short duration. The action potentials were preceded by a slow depolarization and followed by a relatively brief afterhyperpolarization and long-lasting increase in membrane conductance. Current-voltage relations were usually linear between 0 and 80 mV negative to the resting potential. Postsynaptic potentials were evoked in these cells by electrical stimulation of the optic chiasm or contralateral suprachiasmatic nucleus. Both excitatory postsynaptic potentials, which evoked action potentials, and inhibitory postsynaptic potentials were recorded. Synaptic potentials were associated with an increase in membrane conductance. Action potentials evoked by synaptic activation were sometimes followed by up to three small, fast potentials. Small fast potentials were not seen to occur spontaneously, or to follow spontaneous, or current-evoked spikes, nor were they evoked by synaptic potentials that failed to evoke action potentials. The suprachiasmatic nucleus is essential for the generation of normal biological rhythms in mammals. The input it receives from the optic nerve is thought to be important in this role. It is hoped that these preliminary intracellular studies will form a basis for further work on the inherent properties of suprachiasmatic neurones and their responses to visual input.

Animals↗

Properties of motor units in a small foot muscle of Xenopus laevis.

1. Extensor digitorum longus IV muscle (EDL IV) of Xenopus laevis was isolated together with its nerve and the 8th and 9th spinal roots. Motor units were functionally isolated and their properties investigated. 2. The motor unit isometric twitch and tetanic tensions, contraction time and axon conduction time and distance were measured. Axon conduction velocity and twitch:tetanus ratio were calculated. 3. The distributions of motor unit properties were continuous and showed no tendency to separate into types. 4. Axon conduction velocity was directly related to unit tetanic tension (expressed as a percentage of whole muscle tetanic tension and to twitch:tetanus ratio and inversely related to contraction time. Unit tetanic tension was directly related to twitch:tetanus ratio and inversely related to contraction time. Contraction time was inversely related to twitch: tetanus ratio. Possible explanations for these relationships are discussed. 5. The units of EDL IV show a greater resistance to fatigue than fast units of other amphibian muscles. There was no separation of units into fatiguable and fatigue resistant types.

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Polyneural innervation: mechanical properties of overlapping motor units in a small foot muscle of Xenopus laevis.

1. Extensor digitorum longus IV of Xenopus laevis was isolated together with its nerve and the 8th and 9th spinal roots. Motor units were functionally isolated, by splitting and stimulating ventral root filaments. 2. Motor units were stimulated separately and in pairs. Between many pairs, overlap of motor innervation was found (evidence of polyneuronal innervation of muscle fibres). Evidence for overlap was a deficit in the tension developed when the two units were stimulated together compared with the sum of the tetanic tensions developed when the two units were stimulated separately. This provided a measure of the extent of overlap. 3. Polyneuronal innervation was confirmed by intracellular recording from muscle fibres during stimulation of each motor axon. 4. For each motor unit, isometric twitch and tetanic tensions, twitch contraction time and the motor axon conduction time and distance were measured and axon conduction velocity and twitch:tetanus ratio were calculated. 5. The properties of the pairs of motor units found to overlap are reported and marked disparities between the properties of some units in overlapping pairs demonstrated. 6. Frequency distributions for the properties of motor units shown to overlap with others were not significantly different from those for total unit samples., Therefore polyneuronal innervation of muscle fibres occurs throughout the motor unit population of this muscle. 7. In several motor units the isometric twitches of several individual muscle fibres were recorded, each fibre being stimulated by intracellular current injection. It was found that contraction times of single fibres differed by up to 36% between muscle fibres in the same unit and that twitch tension varied by up to 400%.

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Electrical responses of muscle fibres in a small foot muscle of Xenopus laevis.

1. Extensor digitorum longus IV (EDL IV) of Xenopus laevis was isolated together with its nerve and the 8th and 9th spinal roots. Motor units were functionally isolated.2. Glass micro-electrodes were used to penetrate the muscle fibres and to record their electrical responses to stimulation of single motor axons, or the total motor supply to the muscle.3. Three types of electrical response were recorded from muscle fibres: an action potential in response to a single nerve stimulus (type 1), an action potential following repetitive nerve stimulation but not in response to single shocks (type 2) and end-plate potentials which summed to a plateau of depolarization during repetitive nerve stimulation without producing action potentials (type 3).4. In general muscle fibres giving type 1 responses belonged to fast motor units with high twitch: tetanus ratios; those giving type 3 responses, to small units with low twitch: tetanus ratios; and those giving type 2 responses, to units with intermediate properties.5. In many cases the several muscle fibres innervated by a single axon gave different responses to stimulation of that axon and a single muscle fibre might give different responses to stimulation of two single axons. Thus it was not possible to classify motor units or muscle fibres by electrical responses.6. Stimulation of the total motor supply to the muscle favoured the production of type 1 responses so that the proportion of muscle fibres giving type 1 responses was higher when the muscle nerve was stimulated than when single motor axons were stimulated. The proportion of fibres giving type 2 responses was lower, and the proportion of fibres giving type 3 responses was similar, in both cases. The implications of this are discussed.7. Low neuromuscular junctional efficacy is suggested as an explanation for fluctuating twitch tensions and low twitch: tetanus ratios in many motor units in this muscle, and may also affect the activity patterns imposed on the muscle fibres by the motor axons which supply them.

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Observations on the adequacy of breast-feeding.

The faltering of growth which frequently occurs in babies at the age of about 3 months in developing countries is sometimes attributed to insufficient food or to increased exposure to infection. The adequacy of breast-milk as a sole source of food for the young infant is examined in relation to the calculated average requirements for protein and energy. It is concluded that breast milk will fail to cover the energy needs of many infants after about 3 months unless a regulatory mechanism permits infants with higher than average requirements to obtain larger amounts of milk.

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