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Biomedical subjects

M Armstrong-James

Publications and source records attributed to M Armstrong-James.

At least 37 records · Page 2Linked to original sources
PubMed1988

The effect of thiamine deficiency on the structure and physiology of the rat forebrain.

Dietary thiamine deficiency, enhanced by pyrithiamine administration in adult rats, produces overt lesions in the brain that are especially prominent in the thalamus. The present study was undertaken to determine whether the thalamic lesions could be correlated with alterations in the physiological properties of neurons in the thalamus and somatosensory cortex. The regimen for experimentally inducing thiamine deficiency produced large lesions in the thalamus of every case; the lesions included most, if not all, of the neurons in the intralaminar thalamic nuclei. The extent of the lesion in the intralaminar thalamus was highly correlated with the loss of bilaterally synchronous spontaneous activity in the cerebral cortex. This correlation was seen in animals analyzed as early as 1-18 hr after the appearance of opisthotonus, the crisis state of thiamine deficiency, and as late as 2-9 weeks of recovery following thiamine replacement therapy. The loss of bilateral synchronous bursting neuronal activity following intralaminar thalamic lesions is consistent with the proposed role of the intralaminar thalamus as a pacemaker for rhythmic cortical activity (Armstrong-James et al., Exp. Brain Res., 1985; Fox and Armstrong-James, Exp. Brain Res. 63: 505-518, 1986). The location and size of the central lesions within the thalamus suggest that the observed neuronal loss could result from a nonhemorrhagic infarction in the ventromedial branches of the superior cerebellar arteries. Experimental thiamine deficiency also produced alterations in the receptive field properties of the somatosensory cortex neurons in all animals examined. Changes in cortical receptive field properties were correlated with the destruction of sensory relay neurons in the thalamic ventrobasal complex. The loss of the central lateral thalamic input to the cortex and the loss of somatosensory relay neurons in the ventrobasal thalamus in experimental thiamine deficiency produce alterations in cortical function which may contribute to deficits in memory and cognition analogous to those which characterize Korsakoff's psychosis in humans.

Animals↗
PubMed1988

Influence of anesthesia on spontaneous activity and receptive field size of single units in rat Sm1 neocortex.

Spontaneous and cutaneously driven unit activity was recorded in the hindfoot region of rat Sm1 neocortex under controlled intravenous infusion, at three selected rates, of the steroid anesthetic agent Althesin. Increasing depth of anesthesia decreased average spontaneous firing rates of 67 single units from 2.5 to 11 Hz during light anesthesia to 0 to 2.5 Hz in deep anesthesia. Thresholds to cutaneous stimulation for 58 units were innocuous (from 15 to 190 micron) using a 5-ms ramp displacement of the skin in the center receptive field. Responses from 13 sites on the hindfoot were classified according to response probability for each of the 58 units in reply to stimuli at 1.5 times center receptive field threshold. Small receptive fields were seen only under conditions of deep anesthesia, considerable expansion of both center and excitatory surrounds occurring with lighter anesthesia. Mean values for total receptive field size (center plus surround excitatory receptive field) were 10.8, 7.8, and 3.4 sites, respectively, for light, moderate, and deep anesthesia. The size of the receptive field was also influenced by stimulus repetition rate; moderate increases of this and anesthetic depth could eliminate substantial receptive fields. Surround inhibition of evoked activity was more effective in deeper anesthesia with little effect in light anesthesia. We suggest that receptive field expansion in light anesthesia arises from a relative increase in excitability of afferent pathways and an accompanying increase in the preponderance of surround excitation vis à vis surround inhibition.

Alfaxalone Alfadolone Mixture↗
PubMed1987

Spatiotemporal convergence and divergence in the rat S1 "barrel" cortex.

The size and response magnitude of receptive fields were evaluated for cells in the rat cortical barrel-field by using standard vibrissal deflections of 1.14 degrees. Such stimuli fell within the plateau region of stimulus-response curves. The response of all neurones to all vibrissae within and surrounding centre-receptive fields were analysed for probability and latency of response. It was found that cells in supragranular layers had small centre-receptive fields (average 1.6 vibrissae) with small excitatory surrounds (1.5 vibrissae) while cells in the granular layers had small, powerful centre-receptive fields (1.4) with moderately large excitatory surrounds (2.6). Neurones in infragranular layers possessed large but weak centre-receptive fields (2.6) with large surrounds (3.5). Sixty-four neurones in layer IV were studied, the precise locations of which were identified by using dye lesioning and cytochrome oxidase staining. There were no differences in receptive field size for cells within septa and barrel hollows, but the latter were twice as likely to produce two or more spikes per stimulus from the principal vibrissa (65% against 33%). Histological analysis showed that the principal vibrissa was synonymous with the appropriate vibrissa for the barrel on 86% (55 of 64) of occasions. A quantitative analysis of convergent input to three neighbouring barrels (E1, E2, and D1) showed considerable graded overlap of receptive field surrounds, although facial hair adjacent to the mystacial pad only influenced cells on the edge of the barrel-field. Individual vibrissae exhibited significant divergent input to adjacent inappropriate barrels, being preferentially directed to distant septal rather than barrel hollow cells. An analysis of latencies showed that 40% of barrel hollow cells and 48% of barrel septal cells responded at short (less than 10 ms) latencies to their appropriate vibrissa. In contrast, responses to inappropriate vibrissae were overwhelmingly of long latency (10-greater than 30 ms), only 2% of inappropriate responses from barrel hollow cells and 13% from septal cells being of short latency. These results suggest that direct inputs largely project to appropriate barrels. The possibility that divergent inputs are generated by intracortical mechanisms is discussed.

Animals↗
PubMed1986

The role of the anterior intralaminar nuclei and N-methyl D-aspartate receptors in the generation of spontaneous bursts in rat neocortical neurones.

The nature of spontaneous unitary activity of rat neocortex was investigated during slow wave sleep and urethane anaesthesia. Neurones in layer IV and V locations fired in a burst-pause pattern at a low burst repetition rate (0.5-4 per second) during both stage 3/4 sleep and urethane anaesthesia. Occasionally an alternative mode of firing (spindle clusters), associated with focal spindle wave activity, was also found to occur in both states. Using dual microelectrode implants it was found that the onset times of bursts (but not spindle clusters), coincided in the same and opposing cortices, whether in functionally similar or disparate areas. The highest probability was that burst onsets occurred simultaneously (resolution = 2.56 ms, interquartile range = 40 ms). Spontaneous unitary activity was investigated in the thalamus for temporal correlation with spontaneous unitary activity in neocortex under urethane anaesthesia. Neurones of the anterior intralaminar group (aIL) consistently fired in a burst-pause pattern such that each aIL burst showed a strong tendency to precede a cortical burst. Unilateral electrical stimulation of the aIL nuclei evoked widespread bilateral entrainment of cortical bursts. In contrast stimulation of VPl, or cutaneous sites, evoked only short duration spike responses together with burst abolition in the appropriate restricted Sml area. Ionophoresis of NMDA (N-Methyl D-Aspartate) onto Sm1 neurones increased the probability of cortical burst responses to aIL stimulation in addition to decreasing the latency by 20-40 ms (n = 11). Ionophoresis of 2APV (2-amino 5-phosphono valeric acid) caused simultaneous abolition of spontaneous cortical bursts and bursts evoked by aIL stimulation. Short latency responses to cutaneous and VPl stimulation were unaffected by ionophoresis of 2APV sufficient to cause burst elimination, suggesting that this pathway does not operate via a 2APV sensitive receptor mechanism. Anatomical features of the aIL nuclei and their overall cortical projection pattern are discussed in relationship to these findings. The activation of cortical NMDA/APV sensitive receptors by aIL afferents in the "spontaneous" generation of bursts in cortical cells is discussed.

Action Potentials↗
PubMed1985

Modulation of neostriatal activity by iontophoresis of ascorbic acid.

Iontophoresis (20-80 nA) of ascorbic acid (AA) accelerated the firing rate of approximately one-third of the neurons tested in the anteromedial neostriatum of anesthetized rats. When administered to neostriatal neurons that were activated by the simultaneous ejection of glutamic acid (GLU), AA excited more than two-thirds of the cells examined, including many that were not excited by AA alone. At ejection currents above 80 nA, AA further increased the activity of some GLU-activated neurons, but suppressed the firing rate of others. Electrochemical quantification of AA ejection during iontophoresis indicated that the concentration of AA at the tip of the recording electrode was within reasonable physiological limits. It is concluded that endogenous AA may modulate neuronal activity in the neostriatum.

Animals↗
PubMed1985

Threshold effects of N-methyl D-aspartate (NMDA) and 2-amino 5-phosphono valeric acid (2APV) on the spontaneous activity of neocortical single neurones in the urethane anaesthetised rat.

Spontaneous activity of single neurones in neocortex was sampled using pairs of microelectrodes in rats anaesthetised with urethane. In confirmation of previous studies, many cells recorded from middle layers characteristically fired in bursts, the onset times of which were synchronous both unilaterally and bilaterally. Iontophoresis of 2APV onto such cells either caused an abolition of bursts or a reduction in spikes per burst. In the latter case action potentials which occurred later in the burst were preferentially abolished. Iontophoresis of NMDA onto the same cells caused a prolongation of bursts with minimal effect on intraburst interspike interval. In interactive trials with the two drugs the effect of NMDA could be abolished by 2APV, and NMDA counteracted the effect of 2APV. It is concluded that spontaneous burst generation in neocortex during urethane anaesthesia is generated through a cortical NMDA/2APV-sensitive receptor mechanism.

Action Potentials↗
PubMed1983

Effects of ionophoresed noradrenaline on the spontaneous activity of neurones in rat primary somatosensory cortex.

Changes in spontaneous activity of rat S1 cortical neurones with identified receptive fields were investigated in reply to ionophoresed noradrenaline (NA). Extracellular levels of NA were maintained constant by continuous electrochemical analysis at the carbon fibre recording tip of the multibarrel micro-electrode. In the absence of NA there were clear differences in spike amplitude, firing rate and pattern of firing of deep (800-1400 micron) and superficial (0-800 micron) cells. Superficial cells responded to low (5 X 10(-8) to 5 X 10(-7) M) NA concentrations with simple inhibition. Recovery occurred within a minute or so of extracellular NA concentrations falling below detectable (10(-8) M) levels. Increases in local concentration merely stopped cells firing. In contrast, cells located in the deep zone could often be excited by very low NA concentrations (less than 10(-8) M), with inhibition occurring at levels 10-100 times greater. Most cells, however, were inhibited, with threshold doses for a 50% change in firing rate much higher than for superficial cells. Some cells in the deep zone showed sustained increases in firing rate following an ionophoretic trial. This could occur for periods of up to 1 h after ceasing a trial. Such effects could be produced by levels as low as 10(-7) M-NA. Interspike interval analysis for deep cells suggested that their spontaneous activity resembled that established for slow-wave sleep. During and after excitation by NA the pattern of firing of small groups of these cells changed to that established for the waking state. The effect could persist for up to 1 h following a short (2-5 min) ionophoretic trial.

Action Potentials↗
PubMed1982

Dendrite spikes recorded extracellularly from dorsal horn neurones.

(1) Extracellular action potentials were recorded from laminae IV--VI dorsal horn cells, using multibarrel carbon fibre micro electrodes. The amplitude and shape of the extracellular spike, the receptive field, and the response to iontophoretic glutamate ion, were investigated for each cell. (2) Of the 172 units isolated, 48 (28%) could be recorded from over a range of microelectrode tip depths greater than 100 micrometers. The sensitivity of these 'trackable' cells to glutamate was investigated at different depths; 13/48 (27%) had zones where they were insensitive to glutamate. (3) From the data on spike shapes and glutamate sensitivity, it is argued that dendritic spikes can occur in these cells.

Action Potentials↗
PubMed1982

The responses of neurones of the superficial dorsal horn to ionophoretically applied glutamate ion.

Extracellular spikes were recorded from neurones in the marginal zone and substantia gelatinosa of the cat lumbar spinal cord using low-noise carbon fibre microelectrodes. Ionophoretic ejection of glutamate ion was used to distinguish soma/dendrite from axon spikes. The receptive fields of the units and their response to percutaneous electrical stimulation was investigated. The majority of units had low-threshold receptive fields on the hair and skin of the toes and foot. The receptive fields indicated a convergence of different modality afferents onto single cells. Ionophoretic glutamate acted synergistically with the action of the natural transmitter from the low-threshold afferents onto the substantia gelatinosa cells.

Action Potentials↗
PubMed1981

Quantitative ionophoresis of catecholamines using multibarrel carbon fibre microelectrodes.

Carbon fibre microelectrodes can be used to measure the local concentration of ionophoretically ejected catecholamines in vitro or in vivo. The method can also be used to measure the transport number for the materials. The concentration measurement takes about 20 ms and can be repeated at up to about 10 Hz without electrode poisoning or deterioration. This paper describes in detail the methodology of the technique and the apparatus required.

Animals↗
PubMed1980

Quantification of noradrenaline iontophoresis.

Several problems are encountered when iontophoresis is used to study the effects of putative neurotransmitters. The most significant is that it is not usually practical to estimate the concentration of drug obtained at the tip of the microelectrode by a current of a given strength. The usual methods, albeit rarely used, include measurement of transport numbers, the use of ion-sensitive microelectrodes and quantitative fluorescent microscopy. With the exception of the ion-sensitive microelectrodes developed for acetylcholine, these techniques are elaborate and time consuming, and cannot be routinely applied to every electrode used. Furthermore, conventional multibarrel microelectrodes have high-impedance recording barrels and thus often display low signal-to-noise ratios when recording single-cell activity, the noise being increased during iontophoresis. We describe here a technique with largely overcomes the problem of low spike signal-to-noise ratio in conventional multibarrel electrodes, and which, unlike the latter, also allows precise determination of the concentration of noradrenaline in the environment of the cells, which affects its excitability. The recording and iontophoretic properties of these electrodes have been described previously. The use of these electrodes to quantify precisely iontophoresed noradrenaline by adapting polarographic techniques is described.

Animals↗
PubMed1980

Slow waves and unitary activity evoked by cutaneous stimulation from the rat cuneate nucleus.

Depth profiles of averaged evoked potentials (AEPs) and simultaneously generated unitary activity have been recorded from the cuneate nucleus of the rat in response to controlled tactile stimulation of the ipsilateral forepaw. Four separate components of the AEPs were isolated, N1, N2, P, and N3. N1 corresponds to the classical N wave previously described by other workers; four fractions of N1 are described. The classical P wave which follows N1 reverses at 150--350 micrometers depth to become a negative wave of identical time course, the N2 wave, at deeper locations. N2 peaks deeper than N1 within the non-relay portion of the cuneate nucleus, or below in the subnuclear reticular formation where it is the only significant evoked component. Its strong susceptibility to high Mg++ C.S.F. superperfusion suggests a polysynaptic origin. It is argued that the depth distribution and time course of N2 does not support its function relating to depolarisation of primary afferents (PAD) in the vicinity of synaptically driven cuneate cells. Alternative possibilities for its origin are discussed. An additional sustained component of the AEP, the N3 component, is described and evaluated. N3 is co-extensive with N1, has a long time course and simple exponential decay, and is the component most resistant to high Mg++ C.S.F. superperfusion. A similar component to N3 has been described by previous workers in the spinal cord, where it has been shown to arise from glia depolarised by K+ effluxing from discharging afferents and cells. A similar origin for N3 is suggested, and its possible involvement with PAD discussed.

Afferent Pathways↗
PubMed1979

Carbon fibre microelectrodes.

A technique for making recording microelectrodes containing an ultrafine carbon fibre is described. This technique can be used for single- and multi-barrel microelectrodes. These microelectrodes not only have a very low signal-to-noise ratio comparable with that found in tungsten microelectrodes but are simpler to make. When used in a multi-barrel array for iontophoretic application of drugs the carbon fibre microelectrode has many advantages over a fluid electrolyte-filled recording barrel, including very high signal-to-noise ratio and relative immunity to spike distortion during application of iontophoretic current.

Animals↗