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N L Strominger

Publications and source records attributed to N L Strominger.

At least 19 recordsLinked to original sources

Gracile, cuneate, and spinal trigeminal projections to inferior olive in rat and monkey.

In the cat, somatosensory nuclei send substantial projections to the inferior olive, where they terminate in a somatotopic fashion. Although the organization of the cat inferior olive has been used to interpret data from other species, published data suggest this organization may not occur universally. The present study investigated whether the inferior olive in albino rats and cynomolgus monkeys receives the same brainstem somatosensory inputs, whether these inputs are organized somatotopically and, if so, how the organization compares with that in the cat. Projections from the gracile, cuneate and spinal trigeminal nuclei were labeled with wheat germ agglutinin conjugated to horseradish peroxidase or with biotinylated dextran. The results were compared with data from cats (Berkley and Hand [1978] J. Comp. Neurol. 180:253-264). In the rat and monkey, the gracile, cuneate and spinal trigeminal nuclei all project to the contralateral inferior olive, where each nucleus has a distinct preferred terminal field. As in the cat, projections to the medial accessory olive and caudal dorsal accessory olive did not terminate in a precisely organized fashion. Projections to the rostral dorsal accessory olive, however, formed a clear somatotopic map. These somatotopic maps differed from those in the cat in that input from the trigeminal nucleus was confined rostrally, so that the caudal end only received input from the gracile and cuneate nuclei. These data indicate that similar organizational principles characterize the somatosensory projections to the inferior olives of the three species. Nevertheless, distinct species differences occur with regard to the details of this organization.

Animals

The connectivity of the area postrema in the ferret.

The area postrema (AP) is the chemosensitive trigger zone for the emetic reflex. We have investigated the connectivity of the AP and adjacent solitary complex (SC) to identify possible sites of the motor emetic center. The AP and SC were infused with HRP or WGA-HRP in 30 ferrets that were perfused transcardially after 24-72 h. A block from the pons to upper cervical spinal cord, and one with hypothalamus and basal forebrain, was cut at 50 microns, reacted, and mounted. Data support the conclusion, at variance with those from other preparations, that in ferrets the AP has reciprocal connections only with the SC, which serves as a relay in both ascending and descending pathways between AP and higher levels of the neuraxis. Connectivity of the SC with brain stem and forebrain structures including the rostral ventrolateral medulla, parabrachial nuclei, paraventricular nucleus, and amygdala was demonstrated. At least in ferrets, our results suggest that the motor emetic center must be located within the SC. While this may not apply to all species, it is also possible that some reports of AP projections elsewhere were results of label within the SC. Alternatively, the somewhat different pattern of emesis in the ferret as compared to the dog (greater role for vagal inputs in response to radiation and cytotoxic drugs, lesser role for humoral inputs) may reflect differences in AP connectivity.

Animals

The central connections of the vagus nerve in the ferret.

The vagus nerve mediates emesis due to gastric irritation. The central representation of the vagus in the ferret was studied to establish how the nerve is connected to areas important in the regulation of emesis. In a series of 10 ferrets, WGA-HRP injections (10 microliters) were made into the nodose ganglion. After 24-48 h, animals were reanesthetized and perfused transcardially. A block extending from the pons to upper cervical spinal cord was cut at 50 microns and sections reacted. Nodose ganglion injections of WGA-HRP produced labeling of vagal preterminal segments in the ipsilateral dorsal vagal complex including all subnuclei of the solitary complex where the medial and subgelatinous subnuclei received the densest input, the area postrema (AP), which contained a modest amount of terminal label, and the dorsal motor nucleus of the vagus (DMX). Contralateral terminal label, quantitatively much less, was similarly distributed except that within the solitary complex it was limited to the medial and subgelatinous subnuclei. Retrogradely labeled cells formed ipsilateral dorsomedial and ventrolateral columns, corresponding, respectively, to the DMX and the nucleus ambiguus (including retrofacial and retroambiguus).

Animals

Behavioral studies of emetic sensitivity in the ferret.

The ferrets' responsiveness to several known and putative emetic agents was evaluated using a variety of agents that were injected subcutaneously and/or intravenously. Apomorphine was consistently emetic at relatively high doses (100 micrograms/kg) when injected subcutaneously in large male ferrets (> or = 1.4 kg). The responsiveness to apomorphine was anomalous in that subcutaneous injections produced a more consistent response than intravenous ones. In addition, ferrets rapidly become tolerant or tachyphylactic to subcutaneously administered apomorphine. Area postrema ablation, but not abdominal vagotomy, rendered ferrets refractory to the emetic effects of apomorphine. This species, relative to dog and humans, proved to be insensitive to a variety of pharmacologic agents including angiotensin II, gastrin, histamine, Leu-enkephalin, neurotensin, serotonin, and vasopressin. Cisplatin elicited forceful retching and emesis. Emetic responses were obtained with substance P and Met-enkephalin in individual animals but were inconsistent. Sensitivity to DAGO [D-Ala2,MePhe4,Gly-ol5 enkephalin] was variable. Results of this study indicate that the ferret is not an optimal model for all forms of emesis.

Animals

Morphometric and experimental studies of the red nucleus in the albino rat.

Cytoarchitectural observations showed that the red nucleus of the albino rat consists of three distinct neuronal populations. Neurons with coarse Nissl bodies occupy the caudal end of the red nucleus and extend in diminishing number to the rostral tip. Neurons with finely granular Nissl material are the predominant cell type at the rostral tip of the red nucleus and interdigitate with the coarse neurons except at the caudal end of the nucleus. Coarse neurons, in contrast to fine neurons, are multiangular in contour and tend to be larger, although the two populations overlap in size. A population of interneurons, almost entirely smaller than the other cell types and less numerous, is ubiquitous within the red nucleus. Injections of horseradish peroxidase (HRP) at different levels of the spinal cord established that the coarse neurons on the contralateral side are the source of the rubrospinal tract and are topographically organized. The dorsal-medial part of the red nucleus emits axons which project to the cervical cord and the ventral-ventrolateral part of the nucleus to the lumbar cord. The thoracic cord receives projections from rubral neurons at intermediate positions. Further, coarse neurons from the entire rostrocaudal axis of the red nucleus contribute fibers to the rubrospinal tract.

Animals

Localization of adenosine deaminase and adenosine deaminase complexing protein in rabbit brain.

Adenosine deaminase and adenosine deaminase complexing protein have been localized in rabbit brain. Brains fixed in paraformaldehyde or in Clarke's solution were blocked coronally. Blocks from brains fixed in paraformaldehyde were either frozen in liquid nitrogen or embedded in paraffin. Tissue fixed in Clarke's solution was embedded in paraffin. Sections from each block were stained by the peroxidase-antiperoxidase method for adenosine deaminase or complexing protein using affinity-purified goat antibodies. Adenosine deaminase and complexing protein did not co-localize. Adenosine deaminase was detected in oligodendroglia and in endothelial cells lining blood vessels, whereas complexing protein was concentrated in neurons. The subcellular location and appearance of the peroxidase reaction product associated with individual cells was also quite distinctive. The cell bodies of adenosine deaminase-positive oligodendroglia were filled with intense deposits of peroxidase reaction product. In contrast to oligodendroglia, the reaction product associated with most neurons stained for complexing protein was concentrated in granular-appearing cytoplasmic deposits. In some instances, these deposits were clustered about the nuclear membrane. Staining of neurons in the granular layer of cerebellum was an exception. Granule cells were lightly outlined by peroxidase reaction product. Cerebellar islands, also referred to as glomeruli, were stained an intense uniform brown. These results raise the possibility that oligodendroglia and blood vessel endothelia, through the action of adenosine deaminase, might play a role in controlling the concentration of extracellular adenosine in brain. They do not, however, support the suggestion that complexing protein aids in adenosine metabolism by positioning adenosine deaminase on the plasma membrane.

Adenosine Deaminase

Histopathology of the late-onset motor neuron degeneration (Mnd) mutant in the mouse.

The motor neuron degeneration (Mnd) is characterized by a progressive deterioration of motor function (stiff-legged gait, abnormal limb placements and grasping, and finally paralysis; moving from rear to forelimbs). There is a dramatic degeneration of spinal cord motor neurons, more severe in the lumbosacral than in the other regions, as well as variable pathology in the lower cranial nerves. Upper motor neurons of the red nucleus, reticular formation of the pons and medulla, and restricted areas of the cerebral cortex are also affected. Degenerating motor neurons share many characteristics seen in the human disease amyotropic lateral sclerosis, including loss of Nissl substance, increases in lipofuscin and abnormal cytoplasmic inclusions. Additionally, Mnd, like ALS, is a disease of later life.

Amyotrophic Lateral Sclerosis

Bilateral internuclear ophthalmoplegia with absence of convergent eye movements. Clinicopathologic correlation.

A case of bilateral internuclear ophthalmoplegia of long duration with autopsy confirmation is reported. The main features of the syndrome included paresis of ocular adduction upon attempted lateral gaze, horizontal nystagmus in the abducting eye, and an absence of converging eye movements. Examination of Weil-stained sections revealed multiple plaques of demyelination. The medial longitudinal fasciculus was demyelinated bilaterally in the upper pons-caudal midbrain. The oculomotor, trochlear, and abducens nuclei appeared relatively well preserved. The internal capsule was severely damaged. Large cyst-like structures were centered in the anterior limb bilaterally and extended caudally to the level of the genu. Plaques of demyelination were present bilaterally in the posterior limb. The left side of the internal capsule was more severely affected than the right. It is thought that convergence in this case may have been eliminated by interruption of fibers from the frontal eye fields and/or other cortical areas in their descent through the internal capsule.

Carcinoma, Small Cell

Radiation-induced emesis in the dog: effects of lesions and drugs.

Dogs exposed to 8 Gy 60Co gamma mid-abdominal irradiation exhibited emesis with an average latency of 102 min and an average of 7.4 episodes over 96 min. There were no significant changes in dogs subjected to a chronic bilateral subdiaphragmatic vagotomy, but emesis was prevented by ablation of the area postrema. Indomethacin pretreatment also prevented radiation-induced emesis in two of seven dogs and in the remainder reduced the average number of episodes. Domperidone pretreatment prevented radiation-induced emesis in all of four dogs tested. In electrophysiological studies recording from the area postrema the chemosensitive neurons were found to be normally silent in anesthetized preparations but excitable by a variety of emetic agents. After irradiation of the abdomen spontaneously active neurons were found with a discharge pattern that mirrored the behavioral pattern of postirradiation emesis. These studies are consistent with radiation-induced emesis being humorally mediated in the dog and implicate dopamine and/or prostaglandins as possible mediators.

Animals

Banding of rubro-olivary terminations in the principal inferior olivary nucleus of the chimpanzee.

An electrolytic lesion centered just dorsal to, and grazing the superior surface of, the rostral red nucleus (RNr) was produced stereotactically in a single chimpanzee. Perikarya of the ipsilateral RNr exhibited retrograde cell changes, demonstrating interruption of its efferent fibers. The degenerated rubro-olivary tract was followed in silver impregnated material to the ipsilateral compact part of the pedunculopontine nucleus, pontine reticular formation and inferior olivary complex. Within the inferior olivary complex, terminations were banded and restricted to the principal subnucleus.

Animals

Morphological changes in the cochlear nuclear complex in primate phylogeny and development.

The primate cochlear nuclear complex exhibits several characteristic morphological differences in the various primate families from Lorisidae through Hominidae. The most striking differences occur in the organization of the dorsal cochlear nucleus in which the laminar pattern becomes progressively obscured. Granule cells form an external granular layer as well as being intermixed within the molecular and pyramidal layers in slow lorises and squirrel and rhesus monkeys. Whereas a prominent external granular layer remains in chimpanzees, granule cells are scant in other portions of the nucleus. Human adults lack an external granular layer. A small number of granule cells occur but with inconstant distribution. Primates lack the linear array of pyramidal cells oriented perpendicularly to the epithelial surface as seen in cats. The granule cell layer exhibits similar regression in development of the human cochlear complex. The external granular layer is prominent in the fetus but rapidly decreases in size after birth. It achieves its adult form prior to 18 months. The data suggest that neuronal attrition, or programmed cell death, may be the major mechanism accounting for the alterations that occur in the human granule cell layer. Other differences in cytoarchitecture, within the great apes and humans, include decreases in the small and giant cell populations of the cochlear complex. These changes, in consort with the organizational changes and reduction of granule cells as noted above, suggest a trend towards reduced intranuclear integration at the level of the cochlear nucleus coupled with encephalization of the auditory system.

Adult

Effects of age and strain differences on the red nucleus of the mouse mutant Dystonia musculorum.

The mouse mutant Dystonia musculorum exhibits pathological changes in the magnocellular neurons of the red nucleus. The present study shows that allelic differences occur in the age of onset and severity of this pathology. The magnocellular neurons of the Jackson allele (dtJ) almost completely disappear prior to 4 weeks of age while some of these cells are retained in the adult of the Albany strain (dtAlb). However, acetylcholinesterase histochemistry suggests that the remaining rubral neurons in dtAlb are nonfunctional. This pathology may contribute to the severe locomotor disturbances seen in these animals.

Acetylcholinesterase

Neurotoxicity and protein binding of 2,5-hexanedione in the hen.

Previous studies in this laboratory have demonstrated 2,5-dimethylpyrrole adduct formation during in vitro exposure of protein amino groups to the neurotoxic n-hexane metabolite 2,5-hexanedione (2,5-HD). The present investigation reports in vivo pyrrole adduct formation in neural and nonneural protein from 2,5-HD-treated animals. Adult, White-Leghorn hens were given daily doses of either 200 or 70 mg 2,5-HD/kg, po, for up to 55 or 135 days, respectively. Additional animals were given 70 mg/kg for 63 days and then allowed to recover for 72 more days. Protein separation by gel electrophoresis followed by staining with a pyrrole-specific reagent yielded evidence of widespread adduct formation in protein from serum, liver, kidney, brain, and purified myelin. Binding was particularly strong in serum albumin nd myelin basic protein. Quantitation of the adduct in these tissues revealed that its formation reached peak levels at 20 days in high dose and 30 days in low-dose animals. Levels subsequently declined, suggesting the presence of a clearance mechanism capable of removing altered protein during continuing 2,5-HD exposure. Protein from animals on the recovery regimen contained no detectable pyrrole adduct. Pyrrole adduct formation was also detected in neurofilament protein preparations, although protein yields were too low to allow assessment of clearance. Hens at both dosages displayed clinical signs indicative of CNS and PNS neuropathy. Histologic findings included axonal swelling and degeneration in peripheral nerve and some spinal cord nerve tracts. A hypothesis is proposed involving differential clearance of pyrrole adduct from neural vs nonneural tissue to explain the mechanism of action and target organ specificity of 2,5-hexanedione.

Animals

Ascending pathways from the monkey superior colliculus: an autoradiographic analysis.

The autoradiographic tracing method has been used to analyze the distribution of ascending tectofugal pathways in the rhesus monkey. Our findings show that axons which arise from deep collicular neurons terminate within several dorsal thalamic nuclei which in turn project upon the frontal eye fields (area 8) and the inferior parietal lobule (area 7). Both of these cortical areas are functionally quite similar to the deep colliculus, and we suggest that ascending channels from the deep tectum must account, at least in part, for these functional similarities. The present autoradiographs reveal projections to several nuclear zones previously not identified as deep collicular targets in the monkey. Such targets include the visceral cell columns of the oculomotor complex, the rostral interstitial nucleus of the medial longitudinal fasciculus, and the magnocellular division of the ventral anterior nucleus. Deep tectal input also has been shown to terminate quite extensively within the paralamellar region of the mediodorsal nucleus and in the parafascicular nucleus; very little input to the central lateral and centromedian nuclei was observed. Radioisotope injections restricted to the superficial layers reveal dense projections to the parabigeminal nucleus, the pretectum, the inferior and lateral pulvinar nuclei, and to the ventral and dorsal lateral geniculate nuclei. Transported protein within the dorsal lateral geniculate nucleus occupied the "S" layers and the interlaminar zones.

Animals

Sequential auditory and visual discriminations after temporal lobe ablation in monkeys.

Studies in the monkey have shown that cortex outside of the primary projection areas in the superior temporal gyrus and in the inferotemporal region in important for the execution of some auditory and visual descriminations. In this study, six monkeys were trained to perform four auditory and two visual discriminations. Retention tests were given prior to bilateral removal of the anterior part of the lateral surface of the superior temporal gyrus, the inferotemporal region, or both areas together. Superior temporal ablations elicited severe deficits on some auditory discriminations. Inferotemporal ablations caused little or no impairment on visual discriminations. This negative finding is attributed to the sequential rather than spatial mode of presentation of visual stimuli, and to overtraining. A single monkey trained on a spatial visual pattern problem without overtraining was impaired. Another monkey tranied to perform an auditory reverse intensity discrimination exhibited a deficit in ability to perform the problem after removal of auditory cortex within the lateral fissure.

Animals

An autoradiographic study of the rubroolivary tract in the rhesus monkey.

Autoradiographic tracing methods were employed to study the course and distribution of the rubroolivary tract following unilateral injections of tritiated leucine into the rostral red nucleus of seven rhesus monkeys. A topographic organization of projections to the ipsilateral principal nucleus of the inferior olivary complex was demonstrated. Lateral and medial portions of the rostral red nucleus projected to medial parts of the dorsal and ventral laminae of the principal inferior olive respectively; neurons in intermediate lateralities emitted fibers which terminated in lateral parts of the principal olive. Injections involving the oral end of the rostral red nucleus elicited label overlying the medial accessory olive in addition to the principal nucleus. Projections to the medial accessory olive may have arisen from the rostral end of the red nucleus and/or the immediately adjacent tegmentum. There were no projections to the dorsal accessory olive. Fibers of rubral origin also were distributed ipsilaterally to several reticular nuclei including the pedunculopontine, pontis oralis, caudalis, and gigantocellularis.

Animals