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A K Wright

Publications and source records attributed to A K Wright.

At least 19 recordsLinked to original sources
PubMed2004

Death of dopaminergic neurones in the rat substantia nigra can be induced by damage to globus pallidus.

Parkinson's disease is a debilitating disorder that results from the death of dopaminergic neurones in the substantia nigra. Subthalamic nucleus neurones use glutamate as their neurotransmitter and send excitatory projections to the substantia nigra. Changes in both the mean firing rate and firing pattern of neurones of the subthalamic nucleus have been found in patients with this disease. This has led to the suggestion that hyperactivity of the subthalamic nucleus may be involved in the pathology of the dopaminergic neurones. Subthalamic nucleus lesions or treatment with glutamatergic antagonists can be neuroprotective in animal models of Parkinson's disease but until now there has been no direct evidence that hyperactivity of subthalamic nucleus neurones can lead to downstream cell death. Here we show that lesions of the rat globus pallidus (a treatment that has been shown to increase subthalamic nucleus neuronal activity) result in a significant reduction of the number of dopaminergic neurones in the substantia nigra.

Animals↗
PubMed2001

Identification of the source of the bilateral projection system from cortex to somatosensory neostriatum and an exploration of its physiological actions.

Microinjections of cholera toxin B subunit were made into the area of the neostriatum that receives input from the primary somatosensory barrel cortex (SI) in the rat. Studies of the cortices then allowed retrograde identification of the cortical cells supplying the striatal input. When injections were restricted to the neostriatum, retrograde labelling was found in layer V of both SI cortices. Ipsilateral to the injection, cells were retrogradely filled with toxin in all parts of the barrel field, in adjacent parietal cortex, in the motor cortex and in prefrontal areas. A similar distribution across cortical areas was seen contralaterally; however, the stained cells in the SI were between rather than within barrel columns. An earlier anterograde study suggested two inputs from the SI to the neostriatum. The present results indicate that one input to the somatosensory area of the neostriatum arises bilaterally from neurons between the barrels of the SI, while the topographic pathway from below the barrels is present only ipsilaterally. These anatomical results indicate that separate stimulation of the two corticostriatal pathways from the barrel cortex is possible. Electrical stimulation of the contralateral cortex will activate the bilateral pathway, while electrical stimulation of the whisker pads activates the barrels and hence the topographic pathway. Neurons in the somatosensory region of the striatum responded to stimuli in the contralateral cortex and in the contralateral whisker pad. In spite of very different path lengths, stimuli via the two routes gave rise to excitatory postsynaptic potentials in the striatal cells with similar latencies. The excitatory postsynaptic potentials to whisker pad stimulation had a rapid rise time and usually resulted in at least one action potential. Responses to stimulation of the contralateral cortex rose to a peak more slowly and were more variable in latency, but also gave rise to an action potential in the majority of cases. All the neurons had the physiological characteristics of medium-sized densely spiny cells and after intracellular filling with biocytin had the appropriate morphology. In summary, we propose that two corticostriatal pathways arise from layer V cells in the barrel area of the somatosensory cortex; one is bilateral and arises from cells mainly below the septa, while a topographical pathway arises from cells below the barrels. Both pathways can raise the spiny output cells of the striatum to firing threshold. The latencies from the contralateral cortex imply slowly conducting fibres with considerably more temporal dispersion than the pathway from below the barrels, which we excited from the contralateral periphery.

Animals↗
PubMed2000

Corticofugal axons from adjacent 'barrel' columns of rat somatosensory cortex: cortical and thalamic terminal patterns.

The cortical representations of the vibrissae of the rat form a matrix in which each whisker has its own area of cortex, called a 'barrel'. The afferent pathways from the periphery travel first to the trigeminal nuclei and thence via the ventroposteromedial thalamus (VPM) to the cortical barrels have been described in detail. We have studied the output from barrels by filling adjacent areas of the primary somatosensory cortex (SI) with either Phaseolus vulgaris leucoagglutinin (PHA-L) or biotinylated dextran amine (BDA) and demonstrating the course and terminations of the axons that arise within the barrel fields. The method not only dramatically illustrates the previously described corticothalamic pathway to VPM but also demonstrates a strict topography in the cortical afferents to the thalamic reticular nucleus (RT). Cells supplying the RT projection are found below the barrels in layer IV. Connections to the posterior thalamus, on the other hand, have no discernible topography and are derived from cortical areas surrounding the barrels. Thus the outputs of these 'septal' areas return to the region from which they receive thalamic input. The corticocortical connections are also visible in the same material. Contralateral cortical connections arise from the cells of the septa between barrels. The projections to secondary somatosensory area (SII) are mirror images of the barrel pattern in SI with rather more overlap but nonetheless a recognisable topography.

Animals↗
PubMed1999

Double anterograde tracing of outputs from adjacent "barrel columns" of rat somatosensory cortex. Neostriatal projection patterns and terminal ultrastructure.

The sensory input to the neostriatum from groups of cortical cells related to individual facial vibrissae has been investigated at both light- and electron-microscopic resolution. The purpose of the study was to establish the extent to which corticostriatal input maintains the anatomical coding of spatial information that is present in cortex. A double anterograde tracing method was used to identify the output projections from groups of adjacent neurons in different barrel columns, so that the anatomical relationships between two groups could be studied throughout their length. Adjacent whiskers are represented in adjoining cortical barrels and an examination of corticostriatal projections from these reveals two patterns of projection. In one, the anatomical topography is partially preserved; the barrels are represented in adjoining, discrete, areas of the somatosensory neostriatum. In the second projection pattern, the neostriatal innervation is diffuse and adjacent barrels are represented in overlapping regions of the neostriatum. Moreover, the fibres are thinner, have smaller boutons, and are present in both the ipsilateral and contralateral neostriatum. The two systems also enter the neostriatal neuropile separately. The discrete topographic system enters the adjacent neostriatum as collaterals which leave the descending corticofugal fibres at right angles, while the diffuse system enters directly from the corpus callosum at an acute angle. Examination of the neostriatal terminal fields by correlated light and electron microscopy, shows that characteristic axospinous terminals on spiny neurons are made by both groups of cortical fibres, although they differ in their size and morphology. It is concluded that at least two corticostriatal pathways arise from the barrel cortex. One connection maintains some of the anatomical code implicit in the barrel pattern of primary somatosensory cortex, but another, more diffuse, system is overlaid upon it which may carry different information from this complex area of cortex.

3,3'-Diaminobenzidine↗
PubMed1997

Cell-mediated cytolysis of equine herpesvirus-infected cells by leukocytes from young vaccinated horses.

The objective of this study was to determine whether the administration of modified-live equine herpesvirus (EHV-1) to young horses with residual maternal antibodies stimulated EHV-specific cytolytic responses, and whether these responses were crossreactive between EHV-1 and EHV-4. Eighteen clinically normal Belgian cross-foals were used in the study and were commingled in two adjacent pens. Skin biopsies were harvested from 16 foals within 24 h of birth and fibroblast cultures were established, expanded and cryopreserved. Beginning at approximately 10 weeks of age, 10 randomly chosen foals were inoculated on days 0, 21, and 43 of the study with a vaccine containing modified-live EHV-1. Blood mononuclear leukocytes were obtained on days 0, 32, and 50 for the assessment of EHV-specific cytolytic activity using 5 h and 18 h chromium release assays. EHV-1-specific antibodies were assessed by enzyme-linked immunosorbent assay using serum collected on days -21, 0, 32, and 50 of the study. Lymphocyte blastogenic tests and bioassays for interferon activity were conducted on day 50. After two vaccinations, mononuclear leukocytes from seven of ten vaccinated foals had cytolytic activity against autologous EHV-1 cells and leukocytes from six of ten lysed EHV-4-infected cells when tested in an 18 h assay. This activity was enhanced by exogenous interleukin 2 and was markedly reduced using target cells from unrelated horses. Cytotoxicity was not detected in a 5 h assay following in vitro stimulation of leukocytes. After three vaccinations, blood leukocytes from 6/6 vaccinated foals and 0/6 unvaccinated foals had proliferative responses EHV-1. There were no significant differences in interferon production by leukocytes from these foals. Twelve foals tested had low concentrations of (maternal) EHV-1-specific antibody prior to vaccination. Five of eight foals tested had increases in EHV-specific antibodies, while 4/4 commingled unvaccinated foals had a decrease or no change in EHV-specific antibodies. These results demonstrate cytotoxic cellular immune responses can be induced in young horses with maternal antibodies following administration of modified-live vaccine.

Animals↗
PubMed1995

Effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics in neonatal foals.

Thirteen clinically normal Belgian-type foals were used to study the effects of high doses of oxytetracycline on metacarpophalangeal joint kinematics. Seven foals (treatment group) received 2 doses of oxytetracycline (3 g, IV). The first dose was given when foals were 4 days old; the second dose was given 24 hours later. Six foals (control group) received 2 doses of saline (0.9% NaCl) solution (15 ml, IV) at equivalent time periods. All foals were videotaped at a walk twice: immediately prior to the first treatment and 24 hours after the second treatment. The tapes were digitized, and metacarpophalangeal joint angle was measured along the palmar surface of the limb during 3 strides. The angular data were normalized for time, and data from the 3 strides were averaged to describe a representative stride. Repeated measures ANOVA was used to test for differences between groups and within groups over time. Values for stride duration, stance phase percentage, and minimum metacarpophalangeal joint angle obtained before treatment were not significantly different from values obtained after treatment. Maximum metacarpophalangeal joint angle, which occurred during the stance phase of the stride, and range of joint motion were significantly increased for foals in the treatment group, compared with foals in the control group.

Animals↗
PubMed1993

Potassium cyanide protects Escherichia coli from complement killing by the inhibition of C3 convertase activity.

The exact mechanism by which deposited C5b-9 complexes kill Gram-negative bacteria is unclear. It has been proposed that during complement activation the membrane attack complex triggers an energy dependent process in Gram-negative bacteria that mediates destruction of the inner membrane. This observation in part resulted from the survival of Gram-negative bacteria that were incubated with an uncoupler (DNP) or an inhibitor (KCN) of oxidative phosphorylation during complement activation. In a reexamination of this issue we employed potassium cyanide (KCN) to block energy dependent pathways and observed a dose dependent inhibition of C9 uptake on E. coli J5 during serum incubation, suggesting that cyanide was interfering with complement activation. To verify the effect on complement activation we chose specifically to study the effects of KCN on the C3 convertase of the classical pathway. Sensitized sheep erythrocytes were employed as our model system. This system allowed us to construct a series of stable intermediates that were used to test the effect of cyanide on the formation and activity of precursors of the classical pathway C3 convertase. The data illustrate that the concentrations of potassium cyanide that inhibit complement killing of J5 also inhibit C3 convertase activity on sensitized sheep erythrocytes. The results of this study refute the principal observation made by other investigators, that potassium cyanide protects bacteria from complement killing by inhibiting bacterial energy dependent pathways that spark inner membrane destruction. A better scenario is that the organisms survive because cyanide inhibits complement activation.

Animals↗
PubMed1991

Serotonin hyperinnervation after foetal nigra or raphe transplantation in the neostriatum of adult rats.

Embryonic nigral or raphé grafts implanted in the dopamine-depleted neostriatum contain serotonergic neurones and give rise to a serotonergic hyperinnervation of the host striatum. No similar pattern of hyperinnervation is observed in rats with striatal tissue grafts, rats with nigral grafts implanted in the intact striatum, or rats with lesions alone. These observations suggest that striatal dopamine denervation induces some target-derived trophic factors that stimulate fibre growth from serotonergic as well as dopaminergic neurones.

Animals↗
PubMed1990

Glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes are increased in the hypothalamus of androgen-insensitive testicular feminized (Tfm) mice.

In the hypothalamus of androgen-insensitive testicular feminized (Tfm) mice the normal pattern of immunohistochemical staining for glial fibrillary acidic protein (GFAP) is markedly different from normal. Along the borders of the third ventricle and in the dorsomedial and arcuate nuclei, the numbers of stained astrocytes are increased. The usual ordered array of tanycytic processes is obscured by a tangle of GFAP-stained stellate glial cells. GFAP immunostaining in other regions of the Tfm forebrain is similar to that in normal mice. These results suggest that the distribution of reactive glia in the hypothalamus may have been changed as a consequence of the genetic defect in Tfm mice.

Androgen-Insensitivity Syndrome↗
PubMed1990

Distribution and synaptic contacts of the cortical terminals arising from neurons in the rat ventromedial thalamic nucleus.

Injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin within the ventromedial thalamic nucleus resulted in many filled fibres in the frontal areas of rat cerebral cortex. The fibres were restricted to the upper part of layer I except in a small area of motor cortex where terminals were also found in deeper layers. Terminals were also seen in the striatum, in parts of the mesencephalic reticular formation and occasionally in the contralateral ventromedial nucleus. There is some topographical order in the projection with medial and dorsal areas well represented in medial cortex while lateral parts of ventromedial nucleus are more directly related to the cortical area that receives the ventrolateral thalamic nucleus projection. Electron microscopic examination showed the terminals in layer I of cortex making synaptic contact with dendritic spines and small dendritic profiles that showed a very dense postsynaptic specialization. Neurons in the ventromedial nucleus could be antidromically driven from electrode positions along strips of cortex which could not be easily related to any known organizational pattern in the cortex. Thalamic neurons responding antidromically to only one stimulation site were more common when the stimulation was within motor cortical areas, suggesting that in this region a more restricted pattern of termination is the rule.

Animals↗
PubMed1989

Electrophysiological and anatomical observations concerning the pallidostriatal pathway in the rat.

Anatomical studies in several species have demonstrated a pallidostriatal pathway. We employed electrophysiological and anatomical methods to distinguish the neurones of this pathway from the two pallidocortical groups reported in the rat. Injection of fluorescent retrograde tracers, combined with immunohistochemistry for choline acetyltransferase, provided anatomical evidence of the distinction between neurones of the cholinergic pallidocortical projection and pallidal cells retrogradely labelled from the striatum. Extracellular recordings made in the globus pallidus of halothane-anaesthetised rats provided an electrophysiological description of the pallidostriatal pathway. In some animals neurones of this pathway were distinguished from pallidocortical neurones as a stimulating electrode, situated in the crus cerebri, permitted identification of neurones which projected through this region as well as to the striatum. Neither pallidocortical pathway is reported to have descending axons travelling in the crus cerebri at this point. A preliminary electrophysiological study was carried out in rats in which the dopamine-containing cells of substantia nigra had been destroyed by injections of 6-hydroxydopamine at least 6 months prior to the recording. In the globus pallidus on the lesioned side the mean firing rate of neurones was increased compared with controls. No specific change in firing pattern was noted but the neurones were more responsive to striatal stimulation suggesting that long-term dopamine denervation alters the sensitivity of neurones of globus pallidus.

Action Potentials↗
PubMed1982

Orthograde transport of Nuclear yellow: a problem and its solution.

Nuclear yellow injections into the striatum of rats led to staining of both neuronal and glial nuclei even after less than 24 h 'transport time'. The distribution of some of the glial nuclei suggested that the dye was being transported along the striato-nigral pathway. Staining in these areas was greatly reduced if kainic acid was co-injected with the Nuclear yellow.

Animals↗
PubMed1981

The role of dopamine in pontine intracranial self-stimulation: a re-examination of the problem.

Subsequent of their achieving stable rates of responding for electrical stimulation through electrodes implanted in the region of the brachium conjunctivum, rats were anaesthetized and 6-hydroxydopamine injected through an implanted guide tube into the area of lateral hypothalamus in which the ascending axons of dopamine-containing neurones are found. The resultant destruction of these axons had similar temporary effects on the behaviour of the animals whether it was ipsilateral or contralateral to the electrode. It is concluded that nigral or mesolimbic dopaminergic systems are not involved in pontine intracranial self-stimulation behaviour.

Animals↗
PubMed1978

The effect of chronic lithium administration on dopamine metabolism in rat striatum.

Striatal dopamine and its metabolites were studied in rats given lithium chloride in the diet. Results showed an increase in homovanillic acid and 3,4-dihydroxyphenylacetic acid levels but no significant change in dopamine concentration after 3 weeks of lithium administration. There was no change in tyrosine hydroxylase activity after 1, 2, and 3 weeks treatment. The results indicate an increase in the release and turnover of dopamine in the lithium-treated animals.

3,4-Dihydroxyphenylacetic Acid↗