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N L Strominger

Publications and source records attributed to N L Strominger.

At least 19 recordsLinked to original sources

Cross-modal innervation of primary visual cortex by auditory fibers in congenitally anophthalmic mice.

Auditory-visual cross-modal innervation was examined in control (sighted, ZRDCT-N) and congenitally anophthalmic (eyeless, ZRDCT-AN) mice using electrophysiological recording and pathway tracing with carbocyanine dyes. Electrophysiological data demonstrate that the primary visual cortex of congenitally eyeless, blind, mice receives auditory stimuli. Neuroanatomical data demonstrate a direct connection between the inferior colliculus (IC) and visual cortex. Our experiments provide new information about how the brain adapts to the loss of sight.

Adaptation, Physiological↗

Differential actions and excitotoxicity of glutamate agonists on motoneurons in adult mouse cervical spinal cord slices.

Electrical activity was recorded from motoneurons in adult mouse cervical spinal cord (C4-8) slices. Motoneurons showed almost no response to ionophoretic application of N-methyl-D-aspartic acid (NMDA) in both control and Mg(2+)-free media, but very sensitive to kainate (KA) and amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). Bath perfusion of KA, AMPA or glucose/O(2) free Krebs-Ringer solution, but not bath perfusion of NMDA, caused membrane depolarization within 3 min and beading of the dendrite trees after more than 10 min perfusion. Our results indicate that adult motoneurons have few or no NMDA receptors.

Animals↗

Physiological and anatomical properties of the suprachiasmatic nucleus of an anophthalmic mouse.

Congenitally anophthalmic mice (ZRDCT-AN) have circadian rhythms which 'free-run' and are not light modulated. Their rhythms differ from those of controls in: duration of circadian period, length of active phase, and pattern/intensity of activity. Three different populations have been described based upon wheel-running: rhythmic with stable period, rhythmic with unstable period and arrhythmic. Circadian rhythms are generated by neurons in the suprachiasmatic nuclei (SCN) of the hypothalamus. To better understand whether intrinsic properties of SCN neurons differ in anophthalmic and sighted mice, we examined the electrical activity of these neurons in slices, using single unit recordings, ionophoresis and bath perfusion of agonists and antagonists of known SCN neurotransmitters. Lucifer yellow was injected to characterize morphology. In controls, in daytime, units fired at a higher rate (44% at >/=5 Hz) than at night (21% at >/=5 Hz) and with regular interspike intervals versus irregular intervals nocturnally. In anophthalmics four firing patterns were observed as follows: (1) irregular at <5 spikes/s (70% of the total); (2) regular at >/=5 spikes/s; (<10%); (3) irregular bursts (20%); (4) regular bursts (<1%). Most neurons were inhibited by GABA, but a few were excited in controls. Blocking synaptic transmission with low Ca(2+)/high Mg(2+) increased the frequency and regularized the pattern of previously irregular discharges both in anophthalmics and controls. Bicuculline (10(-5) M), a GABA(A) antagonist, had a similar effect. These data suggest that the characteristic irregular firing pattern of anophthalmics, and of controls at night, results from extrinsic, at least in part, GABAergic input.

Action Potentials↗

Rat motoneuron cell death in development correlates with loss of N-methyl-D-aspartate receptors.

New techniques were applied for maintaining viable motoneurons in rat cervical spinal cord slices to study electrical and morphological properties from postnatal day (PD) 2-49. Lucifer Yellow injections showed nine to 12, or more, viable motoneurons/slice at PD2, reduced to two to three in lamina IX by PD9. At PD2 and from PD14 onward healthy motoneurons were electrically similar to those of adults. Motoneurons exhibited variable electrical properties and morphology around PD5. They were sensitive to kainate and AMPA at all ages. The sensitivity to N-methyl-D-aspartate (NMDA) was significant at PD2, less at PD9 and virtually absent at PD14. Our observations suggest that NMDA receptors play a role in regulation of motoneuron survival in the early postnatal period, but are lost from adult motoneurons.

Age Factors↗

Intracellular activity of rat spinal cord motoneurons in slices.

Using a modification of Aghajanian and Rasmussen's techniques, we have developed an adult rat cervical spinal cord slice preparation in which motoneurons remain viable. Key factors are replacement of all sodium ions in the perfusion medium with sucrose during cutting and incubation, and gentle manipulation of the tissues to prevent root damage during removal. Intracellular recordings were confirmed as motoneuronal by intracellular injection of Lucifer yellow, allowing visualization of dendrites and cell body, and showing an axonal bleb at the cut end in the ventral root. Over 50 neurons were recorded for periods of between 30 min and 4 h. Cervical motoneurons (n=10) had an average membrane potential of -62 mV, average input resistance of 24 M(Omega), and showed no spontaneous activity. Ionophoresis application of the glutamate agonists, AMPA and NMDA, revealed potent excitation by AMPA but little or no response to NMDA. While NMDA receptors reportedly are prominent in developing rodent motoneurons, these observations indicate otherwise in the adult. Upon prolonged ionophoresis, or bath application, depolarizing responses to AMPA led to depolarization and spike inactivation that was often irreversible. The apparent lack of desensitization of AMPA responses, usually seen in other neurons, may underlie the unique vulnerability of motoneurons to excitotoxic damage.

Action Potentials↗

Effects of acetylcholine and GABA on neurons in the area postrema of Suncus murinus brainstem slices.

Slices (400 microm) containing the area postrema were prepared from three Japanese house musk shrews. Data reported are from 16 representative units. Units fell into one of three separate groups with spontaneous firing rates of 36-41/s, 16-18/sec. and 6-8/sec., possibly reflecting different set points of an endogenous pacemaker. Most neurons did not respond to ionophoresis of GABA or ACh. In those that did, ACh briefly increased spike frequency in a dose-dependent manner. The firing pattern suggests that the membrane potential was depolarized strongly, coupled with an extremely large conductance increase. Bath perfusion of curare, but not atropine, inhibited the response. Ionophoresis of GABA caused strong inhibition. The data show Suncus AP contains neurons that are sensitive to nicotine and GABA and may be emetogenic.

Acetylcholine↗

Imiquimod-elicited emesis is mediated by the area postrema, but not by direct neuronal activation.

The immunomodulator, imiquimod, has been shown to have antiviral and antitumor properties in animal models. It also has been reported to alter cytokine levels in both animals and humans. However, because imiquimod appeared to be emetic, studies were conducted to determine the degree of sensitivity, and the pathways involved. Subcutaneous administration of > or = 10 mg/kg imiquimod to ferrets elicited emesis with latencies as short as 2'; 12 and 15 mg/kg were optimal doses. Emetic responsiveness was eliminated by complete ablation of the area postrema, but was unaffected by bilateral supradiaphragmatic section of the vagus nerve. This indicates that the emesis is produced by an activation of the chemoreceptor trigger zone B the area postrema. Ferret brain stem slices (450 microm) were preincubated in oxygenated Krebs-Ringer and then mounted in a submerged slice recording chamber. Extracellular recordings of spontaneous and ionophoretically evoked activity of area postrema neurons were obtained for up to 8 h, while the effect of bath-applied imiquimod was determined. Under control conditions, neurons showed a low frequency spontaneous discharge. Introduction of imiquimod (concentration range, 1 x 10(-7) to 5 x 10(-8)M) had no effect on neuronal firing. With ionophoresis of glutamate from an independent micropipette, a brief excitatory response was obtained. We conclude that imiquimod does not directly excite area postrema neurons. It is likely that imiquimod causes synthesis and release of some unknown emetic substance(s), very possibly cytokines.

Aminoquinolines↗

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↗