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N Robbins

Publications and source records attributed to N Robbins.

At least 19 recordsLinked to original sources
PubMed1998

Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1.

Long-term potentiation (LTP) of the Schaffer collateral/commissural inputs to CA1 in the hippocampus was shown to consist of N-methyl-D-aspartate receptor (NMDAR) and voltage-dependent calcium channel (VDCC) dependent forms. In this study, the relative contributions of these two forms of LTP in in vitro hippocampal slices from young (2 mo) and old (24 mo) Fischer 344 rats were examined. Excitatory postsynaptic potentials (EPSP) were recorded extracellularly from stratum radiatum before and after a tetanic stimulus consisting of four 200-Hz, 0.5-s trains given 5 s apart. Under control conditions, a compound LTP consisting of both forms was induced and was similar, in both time course and magnitude, in young and old animals. NMDAR-dependent LTP (nmdaLTP), isolated by the application of 10 microM nifedipine (a voltage-dependent calcium channel blocker), was significantly reduced in magnitude in aged animals. The VDCC dependent form (vdccLTP), isolated by the application of 50 microM D,L-2-amino-5-phosphonvalerate (APV), was significantly larger in aged animals. Although both LTP forms reached stable values 40-60 min posttetanus in young animals, in aged animals vdccLTP increased and nmdaLTP decreased during this time. In both young and old animals, the sum of the two isolated LTP forms approximated the magnitude of the compound LTP, and application of APV and nifedipine or genestein (a tyrosine kinase inhibitor) together blocked potentiation. These results suggest that aging causes a shift in synaptic plasticity from NMDAR-dependent mechanisms to VDCC-dependent mechanisms. The data are consistent with previous findings of increased L-type calcium current and decreased NMDAR number in aged CA1 cells and may help explain age-related deficits in learning and memory.

2-Amino-5-phosphonovalerate↗
PubMed1992

Neural cell adhesion molecule in aged mouse muscle.

Expression of the neural cell adhesion molecule was compared in endplate and non-endplate regions of skeletal muscles of mature and old CBF-1 mice, in order to determine whether age-related changes in neuromuscular morphology were correlated with age changes in neural cell adhesion molecule expression. Three muscles were examined: two (soleus and sternomastoid) showed age-related regionalization of nerve terminals as one manifestation of increased synaptic remodelling while the third (diaphragm) did not. Relative neural cell adhesion molecule content in these muscles was measured by densitometry of immunoblots after concentration by affinity chromatography. Expression of the major 140,000 mol. wt form of neural cell adhesion molecule, which was most abundant in the endplate region, was increased in sternomastoid and soleus of old compared to adult mouse, but was unchanged with age in diaphragm. A 70,000-80,000 mol. wt presumably proteolytic polypeptide fragment of neural cell adhesion molecule was increased in immunoblots of all old muscles. Immunocytochemical studies of skeletal muscles showed no difference in neural cell adhesion molecule cellular distribution in mature vs old mice, but in motor nerve of sternomastoid, the number of neural cell adhesion molecule-positive nerve fibers was increased in old mice. Several lines of evidence indicated that partial denervation was rare in old CBF-1 mice, and therefore could not account for the findings above. Selective increase of 140,000 mol. wt neural cell adhesion molecule expression in the junctional regions of those muscles of old mice which show neuromuscular remodelling indicates that this adhesion molecule may play a role in the age-related instability of motor nerve terminals.

Aging↗
PubMed1992

Compensatory plasticity of aging at the neuromuscular junction.

Several age-related phenomena observed at the neuromuscular junction (NMJ) can be viewed as adaptations to cellular deficits. These compensatory mechanisms, which maintain functional and morphologic integrity, are those present in the adult animal. In the study of compensatory mechanisms with age, the choice of an appropriate animal model is important. Three adaptations are discussed: maintenance or increase of transmitter release despite reduced supply of synaptic vesicles; functional reactive sprouting after partial denervation despite reduced axonal transport; and maintenance of nerve terminal integrity in the face of increased outgrowth and retraction. In all cases, successful adaptation in old animals is obtained at the expense of a more fragile system. Either the compensations themselves or the resulting vulnerability may alter the reactions of the aging nervous system to changes in external and internal milieu.

Adaptation, Physiological↗
PubMed1992

Persistent fever in association with infective endocarditis.

Fever persisting despite adequate antimicrobial therapy for endocarditis can be an ominous sign. To evaluate the significance of persistent fever in this situation, we reviewed the records of patients at three hospital affiliates of Albert Einstein College of Medicine. Twenty-six patients with 27 episodes of endocarditis and fever lasting for > or = 2 weeks despite appropriate antimicrobial therapy were identified and compared with a matched cohort of 26 patients with endocarditis but without prolonged fever. The median duration of fever in the former group was 35 days. Cardiac infection caused fever in 13 of these patients, seven of whom had myocardial abscesses. Additional causes of infection included drug treatment, nosocomial transmission of pathogens, and pulmonary emboli. Sixteen patients required cardiac surgery (seven on an emergent basis), whereas only two controls underwent such a procedure (P < .001). Twenty-two patients with persistent fever and five controls developed nosocomial complications (P < .001). Six patients with fever died, five from endocarditis-related complications. Thus persistent fever often indicates complicated endocarditis. We present an approach for the evaluation of the patients affected by this condition.

Adolescent↗
PubMed1991

Plasticity of presynaptic and postsynaptic elements of neuromuscular junctions repeatedly observed in living adult mice.

In order to assay the extent of ongoing synaptic remodelling in adult mouse neuromuscular junctions, dynamic structural changes of identified neuromuscular junctions were monitored in vivo over periods up to three months. Nerve terminal outgrowths as small as 1 micron were detectable with a new fluorescent tetanus toxin C-fragment stain combined with fluoresceinated alpha-bungarotoxin to stain postsynaptic acetylcholine receptors. With limited illumination, the new stain did not affect miniature endplate potential frequency, nor morphometric parameters of repeatedly observed neuromuscular junctions. At each observation, areas of presynaptic nerve terminal extending beyond underlying acetylcholine receptor ('preprojections'), and areas of acetylcholine receptor without overlying nerve terminal ('postprojections') were measured. Regions of the neuromuscular junction in which nerve terminal-postsynaptic acetylcholine receptor complexes either 'lengthened' or 'shortened' between observations were also measured. The total area of pre- and postprojections (relative to total junctional area) remained the same over three months but most had been replaced; only 20% of preprojections gave rise to lengthenings, the rest retracted or were unchanged. Lengthening and shortening of branches were about 1-2% of junctional area per month. These more permanent changes occurred against a background of ongoing transient nerve terminal outgrowth and retraction (which constituted 80% of all neuromuscular junction shape changes from one observation to the next, compared with 20% for the postsynaptic component). Breaks in the continuity of the underlying acetylcholine receptor were also observed between observations as were instances where acetylcholine receptor continuity was re-established. A newly observed form of plasticity was a shift in position and angle of pre-existing branches. Establishment of new acetylcholine receptor-positive synaptic regions was mostly preceded by nerve terminal outgrowth on the previous observation. In animals in which spontaneous wheel-running increased locomotor activity approximately tenfold over a period of 35 days, the findings were identical to those in unexercised mice. In summary, in the adult neuromuscular junction, the nerve terminal, not the postsynaptic component, is the dynamic entity, continually changing shape on the scale of micrometers, with relatively small permanent changes. These ongoing exploratory excursions may supply the substrate for synaptic plasticity, which would involve regulation of the dynamics or stability of nerve outgrowth.

Animals↗
PubMed1991

Mode of enlargement of young mouse neuromuscular junctions observed repeatedly in vivo with visualization of pre- and postsynaptic borders.

The dynamics of structural remodelling during growth of synapses was studied in identified living neuromuscular junctions observed three times at four-day intervals in three- to five-week-old mice. Nerve terminals and acetylcholine receptors in pectineus muscle were stained and visualized with fluorescent ligands of tetanus toxin C-fragment and alpha-bungarotoxin, respectively. In most observations, about 2.5% of nerve terminal area was observed without underlying acetylcholine receptor (termed 'preprojection'), and about 0.4% of acetylcholine receptor without overlying nerve terminal ('post-projection'). Neither overall synaptic growth nor prevalence of pre- and postprojections was affected by repeated observation. In sequential observations, about 80% of the preprojection area at one observation had acquired underlying acetylcholine receptor four days later, while 20% retracted or showed no change. Although approximately one-half of postprojections were also precursors of synaptic regions, their absolute contribution to synaptic growth was small, and some had originated from nerve terminal retraction. Eight per cent of the disparities between pre- and postsynaptic components in second or third observations were the result of nerve terminal outgrowth or retraction. In the four-day intervals, there was about 7.5% lengthening but also about 3% shortening of synaptic area. Preprojectional induction of acetylcholine receptor accounted for at least 25% of lengthening, and apparent concurrent growth at ends or sides of branches accounted for most of the rest (although level of resolution limits this conclusion). Only about 10% of lengthening was attributable to central intercalary growth. In summary, the pectineus neuromuscular junction grows mainly by nerve terminal outgrowth giving rise four days later to underlying acetylcholine receptor and by conjoint lengthening of synaptic complexes but with relatively little contribution by initial acetylcholine receptor extension or intercalary growth. Growth of the neuromuscular junction is not monotonic: nerve terminals retract and synaptic branches shorten as net lengthening proceeds. Compared with non-growing adult neuromuscular junctions, nerve terminal preprojections in growing neuromuscular functions are more prevalent and more likely to give rise to new synaptic regions.

Aging↗
PubMed1990

Motor nerve terminal restoration after focal destruction in young and old mice.

Regeneration of soleus motor nerve terminals after focal destruction by black widow spider venom (BWSV) or its active factor alpha-latrotoxin (LTx) was compared in young and old CBF-1 mice. The object was to determine whether previously reported delayed regeneration after nerve injury in old rodents was due to altered removal of debris, or delay or aberrancy in structural or functional restoration of the neuromuscular junction. In addition, the use of a new fluorescent technique permitted for the first time quantitation of the accuracy of early nerve terminal regeneration in mammalian muscle. Immunohistochemical and electron micrographic studies showed no age difference in destruction of terminals and removal of debris 2 days after toxin application. The indirect twitch and structural reinnervation (measured with flourescent techniques) returned to an equal extent in young and old mice beginning at 3 days after LTx treatment. BWSV (as opposed to LTx) delayed regeneration 1 day in young but not in old mice. On the first day of reinnervation, there was perisynaptic outgrowth in both young and old mice, although in the latter, there was a higher incidence of aberrant outgrowth. The relation between return of twitch strength and recovery of nerve terminal area (measured in teased zinc iodide-stained preparations) showed no age dependency. We conclude that factors cited to explain altered reactive sprouting in the aging CNS do not apply to regeneration of peripheral motor nerve terminals. However, it is possible that the aberrant regrowth observed at the neuromuscular junction in old mice will pertain to the aging CNS. Altered axonal rather than nerve terminal regeneration is the likely source of delayed peripheral nerve regeneration in old animals.

Aging↗
PubMed1990

Differential effects of age on neuromuscular transmission in partially denervated mouse muscle.

The response of the neuromuscular junction to expansion of the motor unit after partial denervation (section of L5 root) was compared in soleus muscles from young (5-8 month) and old (25-30 month) mice. The object was to determine the relative capacity of young and old motor neurons to adapt to an enlarged functional field of innervation, and to delineate physiological parameters that are compromised under these conditions. Neuromuscular function was studied at 30, 60, and 120 d after partial denervation. The initial (18-23) and postoperative number (5-8) of motor units was the same in both age groups. Twitch strength declined in proportion to loss of motor units at 30 d but returned completely (young) or nearly completely (old) by 60 d. In old but not young muscle, the safety factor (assayed by twitch depression in low calcium) was decreased even before functional sprouting had occurred, indicating a reduced safety factor in nondenervated junctions. The proportion of fibers with "long" latencies (delay between stimulation and endplate potential) increased transiently (at 30 d) in young muscle but persisted without recovery at 120 d in regenerated junctions in old muscle. After partial denervation, decline in miniature endplate potential (mepp) amplitude, in mepp frequency, and in estimated quantal content of evoked release was relatively more pronounced in old than in young mice, and in the case of mepp amplitude and frequency, more persistent. Mepp amplitude was also decreased in presumed nondenervated junctions of old muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1990

Age differences in morphology of reinnervation of partially denervated mouse muscle.

The effect of age on the ability of motor neurons to develop and maintain an enlarged total axonal and synaptic volume was compared in soleus muscles of 5-8-month and 25-30-month mice, 30-120 d after partial denervation. Before and after partial denervation (transection of the L5 root), the total number of muscle fibers was the same in all muscles. However, in young animals, there was only some transient atrophy and hypertrophy mostly receded by 120 d, whereas in old muscle, a more prominent early atrophy was followed by persistent hypertrophy. Ectopic endplates were not found. In zinc-iodide-osmium (ZIO) stained preparations, muscle fibers with small nerve terminals were present at 60 d and were still present in old muscle at 120 d. Fluorescent staining of nerve terminals and acetylcholine receptors revealed that in young muscle, postsynaptic sites were nearly or completely reoccupied by 60 d. In old muscle, about 22% of former junctions were denervated, with the remainder minimally to fully reinnervated. At 60 d and thereafter, collateral sprouts originated from nodes of Ranvier in both young and old muscle and were remyelinated in young but mainly unmyelinated and remarkably tortuous in old animals. These results, confirmed with immunofluorescent strains for myelin basic protein and neurofilaments, account for many of the physiological findings (Jacob and Robbins, 1990). Motor unit size expanded 2.5 times in young and 2 times in old muscle at 60 d after partial denervation. However, the increment in total quantal output and nerve terminal volume per motor neuron was 60-100% greater than control in young but only 20-25% greater in old muscle, with little further recovery. This inability of the motor neuron in old mice to expand the field of innervation may reflect a limitation imposed by reduced axonal transport. The present findings may elucidate the muscle weakness in postpolio syndrome and amyotrophic lateral sclerosis.

Aging↗
PubMed1989

Hand protection and protection from hands: hand-washing, germicides and gloves.

A variety of soaps, detergents, germicides, and protective gloves are available for use by health care workers. Appropriate hand-washing and glove use will reduce the possibility of spread of infectious organisms from patient to staff, from patient to patient, and from staff to patient. Both hand-washing and glove use can have adverse effects. Excessive hand-washing, mechanical irritation from scrubbing, use of germicides, and wearing of gloves can result in irritant and allergic dermatitis. Dermatitis will result in an increased risk of infection to both the worker and the patient.

Cross Infection↗
PubMed1988

Filopodia, lamellipodia and retractions at mouse neuromuscular junctions.

In order to determine if mature motor nerve terminals retain structures associated with development such as filopodia and lamellipodia, we studied whole mounts of mature mouse neuromuscular junctions stained with both fluorescent-labelled tetanus toxin C-fragment and alpha-bungarotoxin, and employed electron microscopy in parallel. The rapid fluorescent stain may be of general usefulness. Both filopodia and lamellipodia were found, extending beyond the border of the established postsynaptic receptors. Filopodia often appeared in clusters, were devoid of a synaptic vesicle antigen, and many withdrew in response to cytochalasin D. Control experiments demonstrated that filopodia were not induced by the toxin treatment. The mean number of filopodia per endplate varied from about one in phasic muscle to three in tonic muscle, and was twice as great in immature mouse muscle. Postsynaptic receptor-rich regions without overlying terminals were less numerous than filopodial and lamellipodial projections without underlying receptors. Electron microscopy showed that lamellipodia contained actin-like filaments and immunoreactivity to actin, but no neurofilaments, microtubules, mitochondria or vesicles. Therefore, these structures would not be visualized by in vivo mitochondrial stains. The lamellipodia protruded into the gap between muscle and a closely overlying Schwann cell process. Lamellipodia occupied about 5% of the linear extent of the terminal arbor in whole mounts, but appeared in 16% of random electron micrographic fields. Thus, the lamellipodia and filopodia typical of developing terminals are present in adulthood and represent a distinctive specialization of the nerve terminal, which may interact with the adjacent Schwann and muscle cell. The frequency of filopodia is a function of age and of muscle or motoneuron type. We suggest that some of the factors known to regulate growth of filopodia and lamellipodia in vitro or in development may continue to act at adult presynaptic nerve terminals.

Animals↗
PubMed1988

Effect of partial denervation and terminal field expansion on neuromuscular transmitter release and nerve terminal structure.

The efficacy of evoked ACh release by intact and newly sprouted terminals in response to partial denervation and expansion of the motor neuron terminal field was studied in mouse soleus muscle after section of the L-5 spinal root. From 2 to 4 d after partial denervation until 90 d later, only 3-7 motor units of the normal 21 remained. Regeneration of the dissected nerve was prevented while the remaining motor units were sprouting. The indirect twitch, which was only 20% of direct twitch tension 2-4 d after nerve section, recovered between 28 and 50 d postoperatively. However, the depression of twitch in low Ca/high Mg solution, which was equal to control 2-3 d postoperatively, was 2-3 times more depressed than control by 50 d and remained so up to 90 d. This indicated persistent reduction of the safety factor in sprouted motor units. Intracellular measurement of quantal content in 0.4 mM Ca, 2.75 mM Mg revealed 2 groups of nerve terminals in partially denervated muscle. The quantal content of the first group was greater than contralateral control at earlier times (28-50 d) and only slightly greater than control later (74 and 90 d). This group consisted of the original undenervated terminals, since it was associated with normal miniature endplate potential (MEPP) frequency and end-plate potential (EPP) latency, and presumably with the class of fibers with normal (zinc iodide osmium-stained) nerve terminal morphology and occasional large myelinated preterminal axons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Acetylcholine receptor availability and transmission efficacy.

Recovery of cholinergic transmission after in vivo blockade with alpha-bungarotoxin (alpha-BTX), and the relationship of recovery to availability of unbound acetylcholine receptors (AChR) were studied in rat diaphragm. When 83% of endplate acetylcholine receptor binding sites were blocked, transmission was absent. A barely detectable recovery of the blocked receptors (25 h after exposure to alpha-bungarotoxin) restored transmission. In fact, 25% of the endplate receptor ACh binding sites were just sufficient for action potential generation. As discussed, slow turnover (t 1/2 = 11 days) of junctional receptors would be sufficient to provide the observed recovery of transmission. Good agreement was observed between the minimum fraction of total receptor sites required for transmission and the computed fraction of maximum quantal release of acetylcholine required to reach threshold. In addition, the data are consistent with the hypothesis that at the neuromuscular junction, AChR exists in considerable excess.

Action Potentials↗
PubMed1987

Statistics of neuromuscular transmitter release in young and old mouse muscle.

1. It was reported previously that in limb muscles of old (27-30 months) CBF-1 mice, quantal content (m) of evoked transmitter release was increased compared to that in young (9-12 months) mice. In diaphragm muscles there was no change with age. The object of the present study was to determine whether the age-related increase in transmitter release was due to increase in the binomial parameter n or the parameter p. The analysis also involved consideration of goodness-of-fit between observed and expected binomial distribution of the data. 2. Spontaneous miniature end-plate potentials (m.e.p.p.s) and evoked end-plate potentials (e.p.p.s) were recorded with intracellular techniques from soleus and diaphragm muscles bathed in low-Ca high-Mg medium. The goodness-of-fit between the observed e.p.p amplitude distribution and that expected from a binomial distribution was evaluated by chi 2 test. 3. In different muscles and at different ages, the percentage of fibres with binomial e.p.p. distributions varied from 17 to 44%, even though in all fibres there was a similar proportionality between direct quantal content and the reciprocal of the square of the coefficient of variation of e.p.p. amplitudes. In addition, apparent graphical agreement between observed and theoretical binomial e.p.p. distributions was often not substantiated by the chi 2 criterion. 4. In soleus muscles from young mice, lowering the stimulus frequency from 10 to 0.5 Hz and shortening the train length from 250 to 100 pulses increased the prevalence of binomial e.p.p. distributions, but the same result was not obtained in diaphragm or soleus muscles from old mice. If the mean amplitude of groups of 10 e.p.p.s in any train showed any drift (greater than 10%) then that train was excluded from the results. Thus, in order to make valid age comparisons, only fibres with binomial e.p.p. distributions were analysed further. 5. There was no change with age in m, n or p in diaphragm muscles, but in soleus muscles from old animals a nearly 2-fold increase in n entirely accounted for the increase in m. 6. If, as proposed by others, n represents the number of release sites, then the ageing soleus neuromuscular junction may have increased numbers or length of active zones or associated membrane components.

Action Potentials↗
PubMed1986

Remodelling of the neuromuscular junction after subtotal disuse.

Within 5 days after reduction of activity of the rat soleus muscle, there was remodelling of the neuromuscular junction. Post-synaptic clefts were shorter, wider, and flatter, whereas nerve terminals showed sprouting and longitudinal distortion. The results, which differ from those found after denervation or total disuse, reveal the plasticity of the mature neuromuscular synapse.

Animals↗