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J Bagust

Publications and source records attributed to J Bagust.

At least 37 records · Page 2Linked to original sources

The effect of bicuculline and baclofen on the dorsal root-ventral root reflex in the isolated spinal cord.

1. In the lumbar spinal cord, 10(-6) M bicuculline reduces the inhibition of the dorsal root-ventral root (DR-VR) reflex produced by lateral stimulation of the spinal cord. The inhibition returns on washing in control artificial cerebrospinal fluid (ACSF). 2. Baclofen (10(-6) M) inhibits the monosynaptic DR-VR reflex which returns on washing in control ACSF. 3. This suggests an involvement of GABAA receptors in the lateral inhibition and GABAB receptors in the DR-VR reflex system. 4. The increased activity seen following bicuculline or tubocurarine probably resets the "set point" of neural activity to a lower level.

Action Potentials↗

Modulation of GABA-mediated inhibition in rat cerebellar slices by benzodiazepine receptor ligands.

1. Extracellular recordings were made from the Purkinje cell layer of rat cerebellar slices. Compounds were perfused over the slice and bipolar stimulating electrodes placed in the external layer of the slice close to the recording electrode. 2. Stimulus-evoked inhibition of Purkinje layer cell activity was sensitive to bicuculline methiodide and picrotoxin, suggesting it was gamma-aminobutyric acid (GABA) mediated. The benzodiazepine ligands RU 32007 and Ro 19-0528 reversibly increased the period of inhibition, as did pentobarbital. This benzodiazepine effect was antagonised by Ro 15-1788. 3. Five inverse agonists all reduced the period of stimulated inhibition and this effect was reversed by Ro 15-1788, suggesting the involvement of benzodiazepine receptors. 4. It is concluded that this system provides a convenient physiological and possibly quantitative model for studying the action of benzodiazepine receptor ligands.

Animals↗

Tubocurarine and strychnine block Renshaw cell inhibition in the isolated mammalian spinal cord.

1. Stimulating a lumbar dorsal root (A) of an isolated mammalian spinal cord preparation sets up a reflex (DR-VR) in the corresponding ventral root (A) of that segment. 2. If an adjacent motor root (B) is antidromically stimulated 100 msec before the dorsal root A is stimulated, it inhibits the ventral root A response. (i.e. Renshaw cell inhibition of A through antidromic stimulation of recurrent collateral of B). 3. Stimulation of the lateral side of the spinal cord 5 mm rostral to the DR-VR reflex sets up a powerful inhibition of the reflex. 4. The inhibition is abolished by tubocurarine, or by strychnine indicating that the lateral stimulation is activating a cholinergic and a glycinergic pathway. 5. Addition of tubocurarine increases the steady "spontaneous" activity in the motor roots. 6. Addition of tubocurarine and 10(-3) M magnesium produces long lasting rhythmic bursting activity in the motor roots that persists even after 45 min of washing. 7. The isolated mammalian spinal cord preparation in addition to having active sensory, motor, and interneurones, has active Renshaw cells that can be studied using this preparation free from any blood-brain barrier and so are easily permeated by tubocurarine, etc.

Action Potentials↗

Quantitative analysis of gamma-aminobutyric acid (GABA) receptors of Purkinje cell layer from rat cerebellar slices.

1. Extracellular recordings were made from Purkinje cell layer of rat cerebellar slices. Cell activity was sensitive to both magnesium and manganese ions. 2. Glutamic and aspartic acids both excited cell activity while gamma-aminobutyric acid (GABA), muscimol, taurine, beta-alanine and delta-aminolaevulinic acid all inhibited activity. 3. The sensitivity to GABA varied with depth while no such effect was observed with muscimol. 4. Bicuculline methiodide, picrotoxin and pitrazepin blocked the action of muscimol with pA2 values of 5.92, 5.97 and 5.71 respectively. 5. The benzodiazepines flurazepam and RU 32007 both potentiated the GABA inhibition and this potentiation was blocked by Ro 15-1788, a benzodiazepine antagonist.

Animals↗

Differential sensitivity of dorsal and ventral root activity to magnesium and 2-amino-5-phosphonovalerate (APV) in an isolated mammalian spinal cord preparation.

Spontaneous activity emerging from the isolated hamster spinal cord simultaneously along the ventral and dorsal lumbar roots was shown by inter-spike interval analysis to have different firing patterns. Ventral root firing was reduced in solutions containing 1 mM magnesium or sub-micromolar concentrations of 2-amino-5-phosphonovalerate (APV), whereas the activity in the dorsal roots was unchanged. Differences in sensitivity to magnesium and APV were also shown on the evoked ventral and dorsal root reflexes, with the dorsal root reflex being unaffected, and the ventral root reflex exhibiting a long latency component that was sensitive to magnesium and APV. These results indicate that NMDA receptors are involved in the generation of part of the ventral root responses in the spinal cord, but not in the generation of the dorsal root reflex and spontaneous dorsal root activity.

2-Amino-5-phosphonovalerate↗

The dorsal root reflex in isolated mammalian spinal cord.

1. The dorsal root reflex has been investigated in an isolated preparation of adult mammalian spinal cord. 2. Both evoked and spontaneous activity can be recorded from the cord in the dorsal spinal roots. 3. The spontaneous activity has a characteristic pattern of firing in bursts of action potentials. Spontaneous and evoked activity are optimum at temperatures between 25 and 27 degrees C; little activity can be detected above 35 degrees C. 4. The spontaneous dorsal root activity has been shown to be correlated with negative potentials in the dorsal horn of the cord, and intracellular recordings made from primary afferent fibres have shown spontaneous primary afferent depolarizations (PAD) which underlie the generation of the spontaneous dorsal root activity. 5. The evoked dorsal root reflex has been shown to spread up to 16 spinal segments both rostrally and caudally from the stimulated dorsal root, and to the contralateral side of the cord. 6. The spontaneous dorsal root activity in widely separated segments has been shown by cross-correlation analysis to be linked both ipsi- and contra-laterally. 7. The significance of such a widespread system for the generation of PAD is discussed.

Afferent Pathways↗

Analysis of extracellular potentials using an IBM PC.

1. A system has been developed for using IBM PC-compatible computers in combination with a Grafitek Data Logging Interface to record spike trains on magentic discs for later analysis. 2. The times and amplitudes of spikes detected on two input channels are recorded, together with a third channel containing information on computer-generated stimuli and keyboard-activated event markers. In excess of 50,000 spikes can be recorded with a computer having 640 k of Random Access Memory. 3. The recorded spike trains can be reconstructed on the computer monitor and keyboard-controlled window discriminators can be used to select the spikes for analysis by amplitude. 4. The same recorded data can be analysed to produce displays of spike count against time, amplitude histograms, inter-spike interval histograms, peri-stimulus time histograms(PSTH), raster displays and auto- and cross-correlations between activity on the two channels. Each spike is identified by number, allowing easy location of the start and finish of the section of data to be analysed, and the PSTH, raster and correlation analyses allow pretriggering to investigate event occurring before stimulation. 5. The axes of the displays histograms can be adjusted to produce optimum displays, and hard copy can be produced on dot matrix printers or digital plotters. 6. Quantitative analysis enables comparison between different recordings and treatments.

Animals↗

The effect of diaminopyridines on the activity recorded in the dorsal roots of isolated spinal cord.

1. The diaminopyridines (DAP) increase the activity recorded in the dorsal roots of an isolated hamster spinal cord preparation. 2. The threshold for 3,4 DAP was 3 x 10(-6) M and the maximum effect was 10(-4) M. The threshold for 2,3 DAP was 3 x 10(-4) M and the maximum effect was at 10(-3) M. The threshold for 2,6 DAP was 10(-4) M and its maximum effect was at 3 x 10(-2) M. 3. When compared with the monoamino pyridines (AP) 4 AP was the most effective and the order of potency was 4 AP greater than 3,4 DAP greater than 2,3 DAP greater than 2 AP = 3 AP greater than 2,6 DAP. 4. Treatment with AP increased the activity simultaneously recorded in the dorsal and ventral roots, but whilst that in the dorsal root continued after washing away the amino pyridine, that in the ventral root ceased for a period of time. 5. There are indications that the amino pyridines may differently affect dorsal and ventral interneurones.

Aminopyridines↗

The effect of aminopyridines on the activity recorded in the dorsal roots of an isolated hamster spinal cord preparation.

1. The aminopyridines (AP) increase the activity recorded on the dorsal roots of an isolated hamster spinal cord preparation. 2. The threshold for 4-AP was 4 X 10(-6) M and the maximum effect was 3 X 10(-5) M. The threshold for 2AP and 3AP was 3 X 10(-5) M and the maximum effect was at 10(-3) M. 3. It took longer for the preparation to recover on washing from treatment with 4-AP than from 2-AP or 3-AP. Washing often showed a transient increase in activity. 4. Treatment with AP changed the pattern of firing so that the activity after treatment and prolonged washing showed a bursting pattern. 5. The activity recorded in the dorsal roots is generated within the spinal cord and may be related to activity of central pattern generators.

Action Potentials↗

Crossed reflex activity in an entire, isolated, spinal cord preparation taken from juvenile rodents.

An entire (not hemisected) spinal cord preparation taken from hamsters weighing up to 40 g is described, in which crossed and uncrossed reflex activity could be evoked from the lumbar ventral roots following stimulation of the lumbar dorsal roots. This activity persisted at higher temperatures in the complete spinal cord than was previously found for hemisected cords, and was obtained in tissue taken from larger animals.

Action Potentials↗

Demonstration of the synaptic origin of primary afferent depolarisation (PAD) in the isolated spinal cord of the hamster.

Intracellular recordings have been made from 31 primary afferent fibres within the dorsal horn of an isolated mammalian spinal cord. In 17 fibres stimulation of an adjacent dorsal root evoked primary afferent depolarization (PAD); these fibres also showed spontaneous depolarizations. Replacement of the calcium in the perfusing medium by manganese blocked both evoked and spontaneous activity showing them to be of synaptic origin. Observations on the effects of current injection and of bicuculline support an involvement of GABA in the generation of PAD.

Action Potentials↗

An investigation of the dorsal root reflex using an in vitro preparation of the hamster spinal cord.

A detailed description is given of an hemisected spinal cord preparation from adult golden hamsters and this preparation has been used to investigate the physiology of the dorsal root reflex. In addition to antidromic reflex discharges which could be recorded from lumbar dorsal roots following stimulation of adjacent dorsal roots or the dorsal columns, spontaneous firing was also recorded from the dorsal roots. This activity reached a peak at 27 degrees C and was abolished at temperatures above 35 degrees C. Both the evoked and the spontaneous dorsal root activity were demonstrated to be travelling antidromically along the dorsal roots out of the cord, and replacement of the calcium in the bathing medium by manganese showed them to be of synaptic origin. Stimulation of a lumbar dorsal root was found to evoke a reflex in up to 4 adjacent spinal segments in both rostral and caudal directions, and a period of depressed activity was demonstrated following both evoked and spontaneous discharges. A time-locked relationship was found between the dorsal root reflex and the slow dorsal horn potential recorded from within the spinal cord.

Animals↗

An isolated mammalian brainstem-spinal cord preparation suitable for the investigation of descending control of motor activity.

An in vitro, hemisected brainstem-spinal cord preparation which allows bulbo-spinal interactions to be investigated, has been developed using 25-33 g golden hamsters. Spinal reflexes showing both monosynaptic and polysynaptic components were recorded from the lumbar ventral roots following stimulation of the corresponding dorsal roots. Trains of conditioning stimuli delivered to the caudal region of the medulla caused inhibition of the monosynaptic component and potentiation of the polysynaptic component of the spinal reflex.

Animals↗

Effects of bath-applied GABA on the firing pattern of cells in an in vitro preparation of mammalian cerebral cortex.

The patterns of spontaneous firing recorded from 25 cells in slice preparations of rat cerebral cortex were characterised using inter-spike interval plots (ISI). Histograms of the ISI showed two peaks having modal values of 20 and 82ms, corresponding to episodes of high frequency bursts of action potentials, and a lower frequency, steady pattern of activity. Bath-applied GABA was shown to reversibly block the bursting activity, but had little effect on the lower frequency component. This effect of GABA could be abolished by the simultaneous application of bicuculline.

Action Potentials↗

Spread of activity in thick cortical slices.

Slices of the hamster cerebral cortex 700-800 micron thick have been demonstrated to be viable when maintained in a bath perfused with oxygenated CSF at 30 ml/min. In such thick slices activity has been shown to spread over both hemispheres following stimulation of the corpus callosum; and seizure activity, suggestive of epilepsy, can be induced by the inclusion of penicillin, pentylinetetrazole, bicuculline or picrotoxin in the CSF.

Animals↗

Synaptic and non-synaptic components of the dorsal horn potential in isolated hamster spinal cord.

Slow negative potentials, evoked by stimulation of the lumbar dorsal roots, have been demonstrated in the dorsal horn of an isolated, hemisected spinal cord preparation from golden hamsters. Paired stimuli revealed a period of partial suppression of this slow potential persisting for up to 2 s following the conditioning stimulus, but with high stimulation frequencies this effect was masked and above 20 Hz a tetanic train of stimuli produced a smoothly rising potential. The response evoked by tetanic stimulation was shown to consist of two components, a manganese-sensitive, synaptically generated component, and a manganese-resistant, frequency-dependent element. Treatment with 10(-4) M 4-aminopyridine blocked the manganese-resistant tetanic response but did not reduce the manganese-sensitive component. Bicuculline, picrotoxin and tubocurare had little effect upon the tetanic response, but 10(-3) M procaine blocked it completely. The possibility that the manganese-resistant response was due to the release of potassium ions is considered.

4-Aminopyridine↗