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Biomedical subjects

O Holmes

Publications and source records attributed to O Holmes.

At least 19 recordsLinked to original sources
PubMed1994

The intracortical neuronal connectivity subserving focal epileptiform activity in rat neocortex.

In the anaesthetized rat, regions of the somatosensory cortex have been subpially isolated, leaving intact the cortical blood supply and the connectivity via the white matter. Application of penicillin or strychnine into layer IV of intact cortex resulted in enhancement of amplitude and prolongation of evoked potentials together with the appearance of spontaneous epileptiform discharges. Within a partially isolated region of cortex, spontaneous and evoked potentials occurred as in normal cortex, but application of convulsant drug resulted in no changes in evoked potentials and in no spontaneous spiking. With incisions for which the surface profile measured 0.9 x 0.9 mm, full-depth isolation resulted in interruption of the propensity for epilepsy, whereas half-depth incisions left epileptic manifestations unimpaired. With the surface profile measuring 0.5 x 0.5 mm, half-depth isolation was sufficient to prevent epileptic activity. Results from isolated regions of various geometries and sizes indicated that the ability of cortical neurones to generate epileptic activity depends on the amount of connectivity with surrounding cortex. The propensity of cortex to become epileptic is thus a mass action effect and the 'epileptic neuronal aggregate' is operationally different from anatomically based modular organizations such as thalamo-cortical or cortico-cortical columns. In the small barrel field of the somatosensory cortex, partial isolations that prevented the appearance of spontaneous epileptiform spiking contained many barrels, indicating that a single thalamo-cortical module contains insufficient inherent lateral connectivity to support epileptiform activity. Theoretical considerations indicated that the excitability of a neurone depends both on its monosynaptic connections with other neurones and on the connectivity of these latter with neurones further afield. The interruption of epileptiform activity by partial isolation could be mimicked by a computer model in which connectivity was mediated via short synaptic paths. The model exhibited self-sustaining synchronized neural activity that could be prevented by interruption solely of polysynaptic paths.

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PubMed1993

Phases in the development of a penicillin epileptiform focus in rat neocortex.

Somatosensory evoked potentials and potentials evoked by direct cortical stimulation were recorded from layer IV of the somatosensory area of the cerebral cortex in urethane anaesthetised rats. Penicillin was expelled electrophoretically from the tip of a drug-filled micropipette at constant rates into layer IV. Small fluxes of penicillin (with electrophoretic currents of -50 to -90 nA) resulted in the appearance, after a delay of 1-2 min, of an enhancement of amplitude in the voltage of both types of evoked potential, unaccompanied by any prolongation of the waveform or spontaneous focal epileptiform discharges. The amplitude of the enhanced evoked potential exhibited a strength-response curve which was a scaled-up version of the curve before penicillin, the scaling factor reflecting the enhancement of amplitude. As the interval between a pair of stimuli was increased, the magnitude of the response to the second stimulus recovered, following a time course similar to that before penicillin. With larger fluxes of penicillin (with electrophoretic currents of -250 to -1000 nA) the amplitude of evoked potentials rose more rapidly and to a higher level; as the concentration of penicillin rose, this enhancement of amplitude led into a second phase, in which there was additionally an increase in the duration of the evoked potentials and the appearance of spontaneous epileptiform discharges. The evoked potentials in this situation showed physiological properties different from those before penicillin application. The strength-response curve exhibited a discontinuity, indicating the evoked potential to be the sum of a physiological response and an epileptiform discharge, the former being graded with stimulus strength and the latter being all or none.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1987

Comparison of penicillin epileptogenesis in rat somatosensory and motor cortex.

The relative sensitivities of somatosensory and motor areas of the cerebral cortex in penicillin epileptogenesis were compared in urethane-anaesthetized rats. Penicillin was applied electrophoretically from a fluid-filled micro-electrode. Spontaneous focal interictal epileptiform discharges were detected by a nearby recording electrode. In motor cortex, every cortical layer was less sensitive in penicillin epileptogenesis than the corresponding layer in somatosensory cortex; epileptic spikes occurred later, were of lower amplitude and were less frequent. In motor cortex, the sensitive depth extended from the deep part of layer III to the upper part of layer V. It seemed possible that penicillin applied to motor cortex might be producing its effects by diffusing back to the sensitive somatosensory area. This was excluded by applying penicillin to motor cortex whilst recording from both somatosensory and motor areas and demonstrating that the spikes were found in motor but not in somatosensory cortex.

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PubMed1984

Bicuculline epileptogenesis in the rat.

Bicuculline has been applied electrophoretically from a fluid filled microelectrode at different depths within the primary somatosensory area of the cerebral cortex of rats anaesthetized with urethane. The delay between onset of drug application at a constant rate and onset of spontaneous focal interictal epileptiform discharges (FIEDs), detected by a nearby recording microelectrode, was least when bicuculline was applied at a depth of 0.65 mm below the pial surface. The subsequent frequency of FIEDs and their voltage excursion were also greatest at this depth. The relationship between the delay of onset of epileptiform spiking and the depth of drug application was very similar to that previously determined for penicillin. This similarity of the sensitivity profiles suggests that the epileptogenic actions of the two agents may be attributable to a common mechanism. At low concentrations, both agents specifically block GABAergic inhibitory synaptic transmission in brain tissue. This is likely to be the mechanism of their epileptogenic effects. Other synaptic and non-synaptic mechanisms cannot, however, be ruled out because of the high concentrations which are achieved locally when a chemical is applied from a point source.

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PubMed1982

Penicillin epileptogenesis in the rat: diffusion and the differential laminar sensitivity of the cortex cerebri.

When penicillin is applied electrophoretically from a fluid-filled microelectrode into the substance of the somatosensory cortex of the rat under urethane anaesthesia, the latent period for production of interictal epileptic spikes is least when the electrode lies 0.7 mm below the cortical surface. With low electrophoretic currents of --50 to 100 nA the increase in latent period as the tip of the electrode is placed further and further away from this level can be quantitatively accounted for by the time taken for penicillin to diffuse and to reach a threshold concentration throughout a critical mass of tissue at the 0.7 mm level. With these low currents, the generators of the interictal spikes are confined to a band of cortex centred at the 0.7 mm level. This is true even when the penicillin is applied away from the sensitive layer; in this circumstance the duration of electrophoresis needed to evoke interictal spikes is greater but when they do eventually appear the spikes are generated at the 0.7 mm layer. Histologically, the sensitive layer has been identified as the deep part of layer III. So far as the generation of interictal spikes is concerned, there is no evidence that, with low electrophoretic currents, penicillin has effects other than at the deep part of layer III; all the available evidence indicates that the penicillin has to diffuse to this layer and produces its effects there.

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PubMed1970

Interaction of cortical evoked potentials in the rat.

1. Unitary and mass potentials were recorded with glass micropipettes at different depths in and around the primary somatosensory area of the cortex in rats anaesthetized with urethane; in addition, surface mass potentials were recorded with chlorided silver ball electrodes. Potentials were evoked by stimuli to the contralateral forepaw and the contralateral cortex. Observations were confined to potentials evoked within 20 msec of stimulation.2. If forepaw stimuli were applied at times when the cortex was not showing spontaneous activity, one component of the evoked response was a widespread depth negativity. This was accompanied by a smaller surface positivity which had the same time course. It could be recorded over the same area of cortex. Unitary activity was found with the same latent period and spatial distribution as the depth negativity. These components of the evoked mass and unitary responses to forepaw stimulation were absent if times of spontaneous cortical activity were chosen for delivering the stimuli.3. Contralateral cortical stimuli evoked mass activity similar to the component of the mass response to forepaw stimulation described in 2. Stimuli given simultaneously to the two sites elicited less unitary activity than the sum of the unitary activity evoked by the two stimuli separately. The mass activity exhibited the interactions which would be expected on the hypothesis that it is generated by the unitary activity. The time course of the interaction is described.4. The interaction was confined to the components of the evoked potentials which were only present if stimuli were applied when the cortex was quiescent. Stimuli applied when the cortex was active evoked mass and unitary potentials which showed no interaction.

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