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F R Edwards

Publications and source records attributed to F R Edwards.

53 records · Page 3Linked to original sources

Nonuniform release probabilities underlie quantal synaptic transmission at a mammalian excitatory central synapse.

1. Excitatory postsynaptic potentials (EPSPs) evoked by impulses in single group I muscle afferents were recorded in dorsal spinocerebellar tract (DSCT) neurons in the spinal cords of anesthetized cats. Fluctuations in the amplitude of these single-fiber EPSPs were determined from measurements of EPSP peak amplitude and contaminating noise (800-4600 trials). 2. In a previous study at this connection, we found that these single-fiber EPSPs fluctuated in amplitude between approximately equal, or quantal, increments. However, these quantal fluctuations could not be described by simple binomial statistics (39). In the present study we have applied further analysis procedures to the same single-fiber EPSPs to formulate a more appropriate probabilistic model of transmission at this connection. 3. In the first stage we have demonstrated that each single-fiber EPSP is composed of the sum of a number (3-30) of uniform quantal events, and that there is extremely little variability in the amplitude of the single quantal event. 4. In a further procedure, we have demonstrated that these quantal fluctuations can be described by a compound binomial model in which each underlying quantal event is associated with a particular, but independent, release probability. The results of this analysis indicate that the probability of transmitter release varies considerably between release sites at this connection. (The use of such a compound binomial model reemphasized previous warnings concerning the interpretation of the results of all statistical models of quantal release. Problems regarding the non-unique nature of N, the total population of quantal events, and other such difficulties are discussed.) 5. A model of transmission at this connection is proposed, in which there are a number of "active" release sites, exhibiting generally high release probabilities, and a number of "reserve" release sites, with zero, or close to zero, release probability. The physiological consequences of such a scheme are discussed.

Afferent Pathways↗

The probabilistic nature of synaptic transmission at a mammalian excitatory central synapse.

The synaptic connection between single group I afferents and dorsal spinocerebellar tract (DSCT) neurons in the cat spinal cord has been studied in an attempt to gain insight into the mechanisms of excitatory synaptic transmission in the mammalian CNS. Fluctuations in the amplitude of single group I fiber EPSPs in DSCT neurons were examined using a numerical deconvolution procedure to reduce the effects of contaminating noise. In general, it was found that single fiber EPSPs fluctuate in peak amplitude between discrete levels separated by equal or quantal increments. Many previous studies have proposed simple binomial statistics as a general model of quantal synaptic transmission. In the present study we show that simple binomial statistics do not describe the fluctuations in amplitude of single group I fiber EPSPs in DSCT neurons. It is suggested that nonuniformities in the probability of transmitter release from release site to release site explain the failure of the binomial model to describe the EPSP fluctuation pattern at this synapse. Nonuniform quantal transmission is proposed as a more adequate description of excitatory synaptic transmission in the mammalian CNS.

Animals↗

Force-sensitive interneurons in the spinal cord of the cat.

The input-output properties of interneurons mediating spinal reflexes were investigated by extracellularly recording the response of interneurons to excitation from muscle receptors in the ankle extensor muscles of decerebrated, spinal cats. A population ofinterneurons in the intermediate region ofthe spinal cord is potently excited by increases in muscle force. Unlike the discharge of Golgi tendon organs, which accurately encodes moment-to-moment variations in the force of a single muscle, the discharge of these interneurons depends in a dynamic and usually nonlinear way on the force in several muscles. Powerful input from unidentified mechanoreceptors in muscle, presumably free nerve endings, is at least partly responsible for these properties. These force-sensitive interneurons are more likely to mediate clasp knife-type inhibition than simple negative force feedback.

Animals↗

Use of BCG as an immunostimulant after resection of carcinoma of the lung: a two-year assessment of a trial of 500 patients.

BCG (Glaxo) (0.5 ml = 5 X 10(6) organisms) was given subdermally to 250 patients ten days after resection of a lung carcinoma to stimulate the immune system. Increased activity of lymphocytes and macrophages could possibly result in the destruction of small extrapulmonary tumour deposits that were previously unidentified. The two-year survival of this group of patients was compared with 250 controls not receiving BCG after operation. A comparative analysis of the sex, histological types, and lymph node involvement in relation to the survivals occurring in these two groups showed that the administration of BCG by the method described produced a numerically greater survival rate, which was particularly noticeable in the women. None of these figures, however, is statistically significant. It would be unwise to draw any final conclusion until a five-year survey has been completed.

BCG Vaccine↗

Use of BCG as an immunostimulant in the surgical treatment of carcinoma of lung: a five-year follow-up report.

Sixty consecutive surviving patients treated with subdermal BCG (5 X 10(6) organisms) have been followed up for five years after resection of lung carcinoma. A control group of the previous 60 consecutive surviving patients not treated with BCG was similarly studied. We found no statistical evidence that the administration of BCG by the method described influenced the five-year survival rate, nor has any effective action upon involved lymph nodes or small metastases been demonstrated.

Aged↗

Interaction between inhibitory and excitatory synaptic potentials at a peripheral neurone.

1. The interaction between inhibitory and excitatory synaptic potentials in neurones lying in the submucous plexus of guinea-pig ileum has been examined. 2. It was found that during an inhibitory conductance change, electrotonic potentials were more depressed in amplitude than were excitatory synaptic potentials. 3. It is suggested that inhibitory conductance changes may have only a slight effect on the impedance seen by excitatory synaptic currents as much of the excitatory synaptic current flow is likely to be capacitive. 4. A part of the depression of excitatory synaptic potential amplitude was not associated with changes in electrical properties of neurones and it is suggested that inhibitory transmitter may reduce the release of excitatory transmitter.

Action Potentials↗

Statistical fluctuations in charge transfer at Ia synapses on spinal motoneurones.

1. Net inward charge is calculated for unitary Ia e.p.s.p.s. evoked in spinal motoneurones. Fluctuations in this charge are used to describe the fluctuations in transmission at the Ia synapse. 2. The statistical details of variation in transmission at Ia synapses are largely obscured by noise, arising from spontaneous activity and recording apparatus. 3. A computational procedure is described, which utilized the measured statistical properties of the recording noise, and the measured charge histogram of the evoked e.p.s.p. (with noise) to calculate the variations in charge due to the e.p.s.p. alone. 4. The fluctuation in charge transmission at Ia synapses are, in general, non-quantal. Nor are they described by binomial or Poisson statistics. 5. It is suggested that the basic mode of transmission at a single terminal is all-or-none. The fluctuations result from the combined effect of failures at several terminals arising from a single afferent fibre. This hypothesis is supported by further analysis of these results in a subsequent paper (Edwards, Redman & Walmysley, 1976a).

Animals↗

Non-quantal fluctuations and transmission failures in charge transfer at Ia synapses on spinal motoneurones.

1. The origins of fluctuations in charge transfer during the generation of Ia e.p.s.p.s have been investigated. The discrete components which make up the fluctuating e.p.s.p. have been separated. 2. Some e.p.s.p.s fluctuate between two different amplitudes and time courses. These fluctuations have been analysed to show that charge transmission always occurs at one synaptic location, but not always at a second synaptic location. 3. The failures in transmission were study by stimulating the afferent fibre at different frequencies. Although different probabilities of failure were obtained at different frequencies, there was no systematic change in probability with increasing frequency. 4. Single afferents were tetanized and histograms of charge transfer computed during post-tetanic potentiation (p.t.p.). Only half of the units studied showed any p.t.p. In those that did, evidence was found for a decrease in the probability of failure during potentiation. 5. The results could not be used to distinguish between failure of the impulse to always propagate into the terminals, and failure of the terminals to release transmitter following adequate depolarization. 6. The fluctuations in transmission at a single synapse can be described by a binomial process with n = 1 and p less than or equal to 1. Junctional mechanisms consistent with this description are discussed. Alternative mechanisms which associate failures with failure of impulse transmission at afferent fibre branch points are also suggested.

Action Potentials↗

The effect of polarizing currents on unitary Ia excitatory post-synaptic potentials evoked in spinal motoneurones.

1. Depolarizing and hyperpolarizing currents were applied to motoneurones in which unitary Ia e.p.s.p.s were evoked. The results concentrate on those e.p.s.p.s which had time courses which were compatible with somatically located synapses. 2. No reversal of these e.p.s.p.s was observed. Depolarizing currents up to 150 nA simply reduced the peak amplitude. 3. Hyperpolarizing currents caused little, if any, increase in the peak amplitude of the e.p.s.p. The time course of decay became briefer as the membrane was hyperpolarized. 4. Changes in decay time course of the e.p.s.p. which accompanied depolarization and hyperpolarization could be attributed to changes in membrane conductances, rather than to changes in synaptic current time course. 5. The failure of the e.p.s.p. to increase with hyperpolarization was shown to be due to the failure of the synaptic current to increase, rather than to the shunting of anomalous rectification. 6. Chemical and electrical transmission are evaluated against these results and those of the preceding papers.

Action Potentials↗

Chondroma of the trachea: report of a case and review of the literature.

Chondroma of the trachea is an extremely rare neoplasm. A patient is described who required surgical treatment for this abnormality on three separate occasions over a nineteen-year period. The last two instances represent either local recurrence or new primary growths. The most recent presentation was that of a very large mediastinal mass causing tracheal compression, dysphagia, and superior vena caval obstruction. The clinical and pathological features of chondromas of the tracheobronchial tree are discussed. Because of its recognized potential for local recurrence, a localized chondroma of the trachea is best managed by tracheal resection.

Chondroma↗