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D M Armstrong

Publications and source records attributed to D M Armstrong.

At least 91 records · Page 5Linked to original sources

Response of septal cholinergic neurons to axotomy.

In the present study we employed quantitative morphometric techniques to assay the response of septal cholinergic neurons following unilateral transection of the fimbria/fornix and supracallosal stria. Analysis of 50-micron-thick tissue sections with a Quantimet 920 image analysis system demonstrated a reduction in ChAT immunoreactivity as early as 1 day following denervation. This decrease was associated with a drop in the number of labeled cells ipsilateral to the lesion and a decrease in the area of cholinergic perikarya on the lesioned and nonlesioned side of the septum. The response at 1 day, however, was transient, and at 4 days the number of labeled neurons was not significantly different from controls. By 8 days we observed a dramatic reduction in the number and size of ChAT-positive cells ipsilateral to the lesion and a reduction in the size of cholinergic perikarya on the contralateral (i.e., nonlesioned) side. These values persisted throughout the remainder of the study. To assess more completely the morphologic response of neurons to axotomy than can be determined in 50-micron-thick tissue sections, we embedded the adjacent immunolabeled tissue section in Epon and then serially sectioned it to a thickness of 0.75-1.0 micron. By using this method, we were able to measure the area, length, and width of the cell, the area of the nucleus and nucleolus, and the position of the nucleus (i.e., eccentricity). Measurements were performed on ChAT-labeled and nonlabeled cells. The results of our studies demonstrate that cholinergic and noncholinergic cells responded to axotomy in a characteristic yet different fashion from each other and that this response could be quantitatively assayed. In general, labeled and nonlabeled cells on the lesioned side of the septum shrink in response to denervation. This shrunken state was reflected in measurements of cellular area, length, width, and nuclear area. Moreover, other measurements of cellular morphology (i.e., area of the nucleolus, position of the nucleus) indicate that none of the neuronal populations examined in the present study displayed morphologic evidence of regeneration. Our results indicate a dramatic loss of cholinergic perikarya ipsilateral to the lesion. Moreover, although a few neurons do persist they do so in a shrunken state. These data provide an essential baseline for the second study in this series, which will evaluate the effect of nerve growth factor on the survival of denervated septal neurons.

Animals↗

The cerebellar corticonuclear projection from lobule Vb/c of the cat anterior lobe: a combined electrophysiological and autoradiographic study. I. Projections from the intermediate region.

The present study examines the projection to the cerebellar nuclei of Purkinje cells in particular sagittal zones within the intermediate region of the cerebellar cortex. The boundaries between the zones were delimited electrophysiologically on the basis of their climbing fibre input so that a small volume (10-120 nl) of 3H-leucine could be injected into the centre of a chosen zone. The subsequent uptake and orthograde transport of labelled material by the Purkinje cells was studied autoradiographically. It was found that the smallest injections resulted in injection sites restricted to a single cortical zone and extremely reproducible results could be obtained using such a combined electrophysiological/autoradiographic technique. Larger injections sometimes spread to a neighbouring zone but the resultant terminal labelling within the deep nuclei was invariably consistent with the results obtained from smaller injections. The c1 and c3 olivocerebellar zones, which are known to receive climbing fibre input transmitted from the ipsilateral forelimb via a dorsal funiculus spino-olivo-cerebellar pathway (DF-SOCP), were found to project to partially overlapping regions within nucleus interpositus anterior (NIA). No projection to nucleus interpositus posterior (NIP) was demonstrated for either zone. No distinction could be seen between the terminal fields for the medial and lateral halves of the c1 zone which are, however, known to receive their climbing fibre input from quite separate regions within the inferior olive. The c2 zone, which was delimited on the basis of its climbing fibre input which is transmitted from both forelimbs via a lateral funiculus SOCP, was found to project exclusively to interpositus posterior. The hemispheral d1 zone was found to project to the transitional region where interpositus anterior and the dentate nucleus adjoin.

Animals↗

The cerebellar corticonuclear projection from lobule Vb/c of the cat anterior lobe: a combined electrophysiological and autoradiographic study. II. Projections from the vermis.

The present study is an investigation of the efferent pathways from Purkinje cells within particular sagittal zones of the vermal region of the cat cerebellar cortex. A combined electrophysiological/autoradiographic technique was used, in which a small volume (10-120 nl) of 3H-leucine was injected into the centre of a chosen cortical zone after the mediolateral extent of the zone had been delimited electrophysiologically on the basis of its climbing fibre input. Study of the uptake and orthograde transport of labelled material by the Purkinje cells showed that the smallest injections gave rise to injection sites which were restricted to a single zone and to terminal labelling which was very reproducible between cases. Larger injections usually resulted in spread of labelled material to neighbouring zones but the resultant distribution of terminal labelling was nevertheless consistent with that arising from smaller injections. The x zone, which receives climbing fibre input transmitted from the ipsilateral forelimb via a dorsal funiculus spino-olivo-cerebellar pathway (DF-SOCP), was found to project to the junctional region between nucleus fastigius and nucleus interpositus posterior (NIP). The b zone, which lies laterally in the vermis and receives climbing fibre input transmitted from both forelimbs (and both hindlimbs) via a slower conducting SOCP, was found to project, not to the cerebellar nuclei proper, but to the ipsilateral lateral vestibular nucleus. The projection of the third zone within the vermis, the a zone, was not examined but it is generally agreed that this zone projects mainly to nucleus fastigius.

Animals↗

A ladder paradigm for studying skilled and adaptive locomotion in the cat.

A circular horizontal ladder is described which is suitable for studying skilled and adaptive locomotion in the cat. Four mechanisms built into the ladder require the animal to adapt its normal walking by making either corrective manoeuvres following an unpredictable disturbance, or anticipatory changes informed by vision. In addition to these features, the ladder incorporates a servo-controlled boom to ensure that the cat is almost completely free of any restraint or drag which might otherwise be imposed by leads carrying foot contact, electromyographic and neuronal signals from the animal to the recording equipment. The apparatus is proving in use to be reliable and easy to operate, and our preliminary results clearly implicate supraspinal motor centres in controlling the skilled and adaptive behaviour which the ladder requires.

Adaptation, Physiological↗

Relation of pontine choline acetyltransferase immunoreactive neurons with cells which increase discharge during REM sleep.

The purpose of this study was to determine whether neurons in the medial pontine reticular formation with high discharge rates during REM sleep could be localized in regions of the brainstem having neurons displaying choline acetyltransferase immunoreactivity. Six cats were implanted with sleep recording electrodes and microwires to record extracellular potentials of neurons in the pontine reticular formation. Single-units with a S:N ratio greater than 2:1 were recorded for at least two REM sleep cycles. A total of 49 units was recorded from the pontine reticular formation at medial-lateral planes ranging from 0.8 to 3.7 mm. The greatest proportion of the units (28.6%) showed highest discharge during active waking and phasic REM sleep compared to quiet waking, non-REM sleep, transition into REM sleep or quiet REM sleep periods. A percentage (20.4%) of the cells had high discharge associated with phasic REM sleep periods while 8.2% of the cells showed a progressive increase in discharge from waking to REM sleep. Subsequent examination of the distribution of choline acetyltransferase immunoreactive cells in the PRF revealed that cells showing high discharge during REM sleep were not localized near presumed cholinergic neurons. Indeed, we did not find any ChAT immunoreactive somata in the medial PRF, an area which has traditionally been implicated in the generation of REM sleep. These results suggest that while increased discharge of PRF cells may be instrumental to REM sleep generation, these cells are not cholinergic.

Animals↗

Complex spikes in Purkinje cells in the lateral vermis (b zone) of the cat cerebellum during locomotion.

1. Complex spikes (c.s.s) due to climbing fibre input were recorded from forty-one Purkinje cells in the lateral part of the vermis (i.e. the b zone) of lobule V of the cerebellum in cats walking on a moving belt or a horizontal ladder. Most cells were near the tips of the folia making up the lobule and some were shown by antidromic invasion to project to the ipsilateral lateral vestibular nucleus. In all cells c.s.s. could be evoked through mechanical stimuli delivered manually to the neck and/or trunk and/or the limb girdles and/or the proximal parts of the limbs. 2. During walking c.s.s. occurred at rates which ranged in different cells from 0.8 to 2.55/s (i.e. ca. 0.8 to 2/step). When activity was averaged across many successive steps the probability of c.s. occurrence was never completely constant throughout the step cycle, but no tendency was detected for c.s.s to recur at any precisely fixed time during the cycle. 3. When ladder locomotion was perturbed because a rung underwent an unexpected 2 cm descent when stepped on, some cells generated a c.s. at short latency in a proportion of trials. Such responses were well time-locked to the onset of rung movement but not to its cessation (which they often preceded). 4. For perturbations of either forelimb the earliest displacement-related c.s. occurred in different cells between 40 and 64 ms after the onset of rung movement. In different cells c.s.s occurred in from one out of five to three out of four perturbed steps (mean ca. two out of five steps). Eight out of seventeen cells responded to perturbation of the forelimb ipsilateral to the cell and five out of ten responded to contralateral perturbations. 5. Perturbation of the ipsilateral hind limb was accompanied by c.s.s in four out of nine cells and latency was usually longer (by ca. 30-40 ms). One cell showed a decrease in the probability of c.s. occurrence. Insufficient data were obtained for a systematic study of responsiveness to perturbation of the contralateral hind limb. 6. Cells showed different patterns of limb specificity, responding to perturbation of one, two or all of the three limbs studied. In total, c.s.s accompanied perturbation of at least one limb in thirteen out of twenty cells studied (65%).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Choline acetyltransferase immunoreactivity in neuritic plaques of Alzheimer brain.

We have observed dystrophic choline acetyltransferase (ChAT)-positive processes surrounding the amyloid core of neuritic plaques in human neocortex, amygdala and hippocampus, using a polyclonal anti-human ChAT antiserum. These data, and those from studies of the aged monkey by other investigators, provide a morphologic counterpart for the biochemical abnormality of the cholinergic system in Alzheimer's disease and senile dementia of the Alzheimer type.

Aged↗

Ultrastructural characterization of choline acetyltransferase-containing neurons in the basal forebrain of rat: evidence for a cholinergic innervation of intracerebral blood vessels.

The ultrastructural morphology and vascular associations of cholinergic neurons in the horizontal limb of the nucleus of the diagonal band of Broca (nDBBhl) and amygdala of rat were determined by the immunocytochemical localization of choline acetyltransferase (ChAT), the acetylcholine biosynthetic enzyme. Within the nDBBhl peroxidase reaction product was distributed throughout the cytoplasm of selectively labeled neuronal perikarya and dendrites. Labeled perikarya were characterized by an oval cell body (7-10 microns X 17-26 microns in diameter) in which was located a large nucleus and often a prominent nucleolus. Dendrites were by far the most numerous immuno-labeled profiles in the nDBBhl. The labeled dendrites had a cross-sectional diameter of 0.4-4.6 microns and contained numerous mitochondria and microtubules. Approximately 10% of all immunolabeled dendrites received synaptic contacts from unlabeled presynaptic boutons. In contrast to the relatively large number of ChAT-labeled dendrites within the nDBBhl, ChAT-positive axons were less frequently observed and immunolabeled axon terminals were never detected. The labeled axons had an outside diameter of 0.4-1.4 micron and were myelinated. The absence or relative paucity of immunolabeled terminals in the nDBBhl indicates that most if not all of the cholinergic perikarya within this nucleus are efferent projection neurons. The nDBB is known to have widespread projections to many areas of the neocortex, hippocampus, and amygdala. In the present study we examined the amygdala and observed many ChAT-labeled axon boutons. The immunolabeled varicosities contained numerous agranular vesicles and although ChAT-positive terminals were in direct contact with unlabeled neuronal elements within the amygdala, few if any synaptic densities were detected in a single plane of section. With respect to the vasculature, immunolabeled perikarya and dendrites within the nDBBhl and axon terminals in the amygdala were often in direct apposition to blood vessels. In many instances the labeled profile was observed lying directly on the basal lamina of a capillary endothelial cell. In no instance, however, were membrane densities observed. The presence of cholinergic neuronal elements contacting the vessel wall provides morphologic evidence suggesting that the neurogenic control of cerebral vasculature is in part mediated via a cholinergic mechanism.

Amygdala↗

The distribution of choline acetyltransferase in the rat amygdaloid complex and adjacent cortical areas, as determined by quantitative micro-assay and immunohistochemistry.

The distribution of choline acetyltransferase (ChAT) within the amygdaloid complex has been studied to evaluate what should primarily represent the terminal field of the cholinergic projection from the basal forebrain. Two currently available methods have been combined for the comparison: immunohistochemistry with a monoclonal antibody against ChAT, by a double peroxidase-antiperoxidase procedure, and quantitative histochemistry involving micro-assay of the ChAT activity of contiguous microdissected samples. Both methods indicate prominent ChAT activity in the basolateral amygdaloid nucleus (especially rostrally), the nucleus of the lateral olfactory tract (especially layer II), and the amygdalohippocampal area. Regions of lower ChAT activity were not accurately represented by the immunohistochemistry, but could be discriminated by the quantitative assays. Lowest activity was found in the medial nucleus of the amygdala. Most other regions had activities at least as high as average brain or neocortex. Gradients of enzyme activity were found within several regions, including the basolateral and lateral amygdaloid nuclei and the nearby posterior piriform cortex. In the piriform cortex, a region of particularly high ChAT activity was found at its medial edge near the nucleus of the lateral olfactory tract. The immunohistochemical method shows a few intensely reactive somata in layer III within this zone. Comparison of the results seen with immunohistochemistry and quantitative histochemistry suggests an advantage in using them together, since their respective strengths and weaknesses tend to complement each other.

Amygdala↗

Neuropeptides and NADPH-diaphorase activity in the ascending cholinergic reticular system of the rat.

A major group of cholinergic neurons is present in the midbrain and pontine tegmentum. These cells could be selectively stained using either monoclonal antibodies to choline acetyltransferase, the pharmacohistochemical acetylcholinesterase procedure, or reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry. Using these three techniques, the precise distribution of this cell group was determined. By combining these techniques with immunohistochemical staining for various neuropeptides, examples of peptide-cholinergic coexistence could be demonstrated in this cell group. Approximately 30% of these cholinergic neurons displayed substance P immunoreactivity. Most of these cells also showed corticotropin-releasing factor immunoreactivity and bombesin/gastrin-releasing peptide immunoreactivity. These results therefore provide evidence for the coexistence of various neuropeptides together with NADPH-diaphorase activity in the ascending cholinergic reticular system.

Acetylcholinesterase↗

Professional behavior in collaborative practice.

Cost containment, increased severity of illness, earlier patient discharge, and high staff turnover are causing nurse executives to implement new systems of health care delivery. One such delivery system, collaborative practice, strives to maximize efficient and effective use of staff, to improve nurse retention, and to enhance patient care. The authors present one approach to implementing collaborative practice and the empirical findings related to the system's impact on physician-nurse professionalism.

Connecticut↗

China visit.

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China↗

Somatostatin-like immunoreactivity within neuritic plaques.

Alzheimer's disease or senile dementia of the Alzheimer type (SDAT) is a progressive neurodegenerative disease that is characterized pathologically by two types of microscopic lesions in the neocortex: the neurofibrillary tangle and neuritic plaque. The concentration of neuritic plaques is correlated with significant reductions in the level of specific neurotransmitter and neuropeptide systems in autopsied brains of patients with SDAT, including decreased amounts of the tetradecapeptide, somatostatin. The clinical effects of reduced cortical somatostatin activity in patients with SDAT is unclear, nor is it known whether somatostatinergic neurons participate in either lesion. In the present study we employed light microscopic immunocytochemistry to determine whether somatostatin-containing neurons participate in the formation of neuritic plaques. Examination of selected cortical regions from autopsied brains revealed 20-50% of all neuritic plaques contained somatostatin-positive profiles indicating that processes of somatostatinergic neurons are associated with neuritic plaque formation.

Aged↗

Substance P immunoreactivity within neuritic plaques.

In the present immunocytochemical study we examined brain tissue of patients with Alzheimer's disease in order to determine the relationship of substance P (SP)-labeled processes to neuritic plaques. Swollen neuropeptidergic processes were consistently observed within a relatively small percentage of the plaques. These data provide a morphologic correlate to the biochemical finding that SP levels are reduced in the brain tissue of patients with Alzheimer's disease, and further indicate that Alzheimer's disease affects multiple neurotransmitter and neuropeptide systems.

Aged↗

Origin in the medial accessory olive of climbing fibres to the x and lateral c1 zones of the cat cerebellum: a combined electrophysiological/WGA-HRP investigation.

The climbing fibres to the x and lateral c1 zones of the anterior lobe of the cerebellum arise as branches of common stem olivary axons. Anatomical studies have shown that the c1 zone receives its climbing fibres from the dorsal accessory olive (DAO). It has, therefore, been assumed that the x-zone also receives its climbing fibres from this olivary subnucleus. The present study demonstrates that both the x-zone and the lateral part of the c1 zone in fact receive their climbing fibre input from the middle portion of the medial accessory olive (MAO) (approximate antero-postero-levels P10-13). Electrophysiological techniques were used to define the extent of these cerebellar zones and small volumes (15-50 nl) of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) were pressure injected into the defined zone. These small pressure injections resulted in injection sites with minimal spread to adjacent zones. The sensitive tetramethylbenzidine (TMB) reaction was used to visualize both the injection site and retrogradely labelled cells in the inferior olive. This combination of electrophysiological and neuroanatomical techniques gave extremely reproducible results. The results suggest that the zone previously named lateral c1 would be better designated cx.

Animals↗