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1.
Amendola J Gueritaud JP Lamotte d'Incamps B Bories C Liabeuf S Allene C Pambo-Pambo A Durand J 《Archives italiennes de biologie》2007,145(3-4):311-323
Antidromically identified lumbar motoneurons intracellularly recorded in the entire brainstem/spinal cord preparation isolated from SOD1(G85R) postnatal mice (P3-P10) were labelled with neurobiotin and fully reconstructed in 3D from serial sections in order to analyse their morphology. This staining procedure revealed differences between WT and SOD1(G85R) dendritic trees for most metric and topologic parameters analyzed. A highly complex morphology of SOD1(G85R) motoneurons dendrites (increased number of branching points and terminations) was found and the dendritic trees were longer compared to the WT motoneurons. These morphological changes observed in P8-P9 motoneurons mice occurred concomitantly with a decrease in the input resistance and gain. During electrophysiological recordings, four patterns of discharge were observed in response to ramp stimulations, that were equally distributed in WT and SOD1(G85R) motoneurons. In slice preparation, whole cell patch-clamp recordings made from developing motoneurons in SOD1(G85R) and double transgenic SOD1(G93A)/Hb9-eGFP mice showed that Riluzole, a blocker of persistent inward sodium conductance, altered the repetitive firing in a similar way for the 2 strains. These results show that the SOD1 mutations linked to familial ALS alter the development of the electrical and morphological properties of lumbar motoneurons. 相似文献
2.
I. B. Kulagina 《Neurophysiology》2012,43(5):335-343
Mathematical models of abducens motoneurons with reconstructed dendritic arborizations were investigated. The two types of models differed from each other
in electrical properties of the dendrites, either passive (model group 1) or active and non-linear (model group 2). The relations
between morphology of the dendrites, their electrical transfer characteristics, and formation of impulse patterns at the cell
output were studied under conditions of tonic activation of glutamatergic (NMDA-type) excitatory synapses homogeneously distributed
over the dendrites. For reconstructed dendritic arborizations, their morphometric characteristics (size, complexity, and metrical
asymmetry) and electrical ones (somatopetal current transfer effectiveness function and sensitivity of the latter to variations
of the homogeneous membrane conductivity) were computed. Changes in the membrane potential were also studied in different
parts of the dendritic arborization during generation of various patterns of discharges of action potentials (APs) at the
neuronal output under different intensities of synaptic activation; this allowed us to reveal “spatial signatures” of the
above-mentioned temporal patterns. The output patterns and their “spatial signatures” changed in a certain manner with increase
in the intensity of synaptic activation. A simple periodical discharge of low-frequency APs with constant interspike intervals
was replaced by a complex periodical or nonperiodical (stochastic) bursting pattern, which then was replaced again by a simple
rhythmic but high-frequency discharge. Simple periodical patterns were associated with generation of synchronous oscillatory
dendritic depolarizations phase-shifted in metrically asymmetrical parts of the arborization. In the case of generation of
complex periodical or stochastic patterns, depolarization processes in asymmetrical dendritic parts were asynchronous and
differed from each other in their amplitude and duration. Such a structure-dependent repertoire of output discharge patterns
was quite compatible with that observed earlier in examined simulated neocortical pyramidal and cerebellar Purkinje neurons.
This fact is indicative of a possible similarity of the rules governing the formation of specific output patterns in neurons
with active membrane properties of the dendrites based on intrinsic mophological/functional features of the dendritic arborization
of a given neuron. 相似文献
3.
Jianghong Tian Tetsuya Iwasaki Wolfgang Otto Friesen 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2010,196(2):123-136
Animal locomotion results from muscle contraction and relaxation cycles that are generated within the central nervous system
and then are relayed to the periphery by motoneurons. Thus, motoneuron function is an essential element for understanding
control of animal locomotion. This paper presents motoneuron input–output relationships, including impulse adaptation, in
the medicinal leech. We found that although frequency-current graphs generated by passing 1-s current pulses in neuron somata
were non-linear, peak and steady-state graphs of frequency against membrane potential were linear, with slopes of 5.2 and
2.9 Hz/mV, respectively. Systems analysis of impulse frequency adaptation revealed a static threshold nonlinearity at −43 mV
(impulse threshold) and a single time constant (τ = 88 ms). This simple model accurately predicts motoneuron impulse frequency when tested by intracellular injection of sinusoidal
current. We investigated electrical coupling within motoneurons by modeling these as three-compartment structures. This model,
combined with the membrane potential–impulse frequency relationship, accurately predicted motoneuron impulse frequency from
intracellular records of soma potentials obtained during fictive swimming. A corollary result was that the product of soma-to-neurite
and neurite-to-soma coupling coefficients in leech motoneurons is large, 0.85, implying that the soma and neurite are electrically
compact. 相似文献
4.
Léa Milan Gilles Courtand Laura Cardoit Frédérique Masmejean Grégory Barrière Jean-René Cazalets Maurice Garret Sandrine S. Bertrand 《PloS one》2015,10(8)
Large cholinergic synaptic terminals known as C-boutons densely innervate the soma and proximal dendrites of motoneurons that are prone to neurodegeneration in amyotrophic lateral sclerosis (ALS). Studies using the Cu/Zn-superoxide dismutase (SOD1) mouse model of ALS have generated conflicting data regarding C-bouton alterations exhibited during ALS pathogenesis. In the present work, a longitudinal study combining immunohistochemistry, biochemical approaches and extra- and intra-cellular electrophysiological recordings revealed that the whole spinal cholinergic system is modified in the SOD1 mouse model of ALS compared to wild type (WT) mice as early as the second postnatal week. In WT motoneurons, both C-bouton terminals and associated M2 postsynaptic receptors presented a complex age-related dynamic that appeared completely disrupted in SOD1 motoneurons. Indeed, parallel to C-bouton morphological alterations, analysis of confocal images revealed a clustering process of M2 receptors during WT motoneuron development and maturation that was absent in SOD1 motoneurons. Our data demonstrated for the first time that the lamina X cholinergic interneurons, the neuronal source of C-boutons, are over-abundant in high lumbar segments in SOD1 mice and are subject to neurodegeneration in the SOD1 animal model. Finally, we showed that early C-bouton system alterations have no physiological impact on the cholinergic neuromodulation of newborn motoneurons. Altogether, these data suggest a complete reconfiguration of the spinal cholinergic system in SOD1 spinal networks that could be part of the compensatory mechanisms established during spinal development. 相似文献
5.
Heldoorn M Marani E Leeuwen JL Vanderschoot J 《Archives of physiology and biochemistry》2003,111(3):193-201
This article discusses a model of the electrical behavior of an external urethral sphincter motoneuron, based on morphological parameters like soma size, dendritic diameters and spatial dendritic configuration, and several electrical parameters. Because experimental data about the exact ion conductance mix of external urethral sphincter neurons is scarce, the gaps in knowledge about external urethral sphincter motoneurons were filled in with known data of alpha-motoneurons. The constructed compartmental model of motoneurons of Onuf's nucleus contains six voltage-dependent ionic conductances: a fast sodium and potassium conductance and an anomalous rectifier in the soma; a fast delayed rectifier type potassium conductance and a fast sodium conductance in the initial axon segment; an L-type calcium channel in the dendritic compartments. This paper considers the simulation of external urethral sphincter motoneuron responses to current injections that evoke bistable behavior. Simulations show self-sustained discharge following a depolarizing pulse through the microelectrode; the firing was subsequently terminated by a short hyperpolarizing pulse. This behavior is highly functional for neurons that have to exhibit prolonged activation during sphincter closure. In addition to these 'on' and 'off ' responses, we also observed a particular firing behavior in response to long-lasting triangular current pulses. When the depolarizing current was slowly increased and then decreased (triangular pulse) the firing frequency was higher during the descending phase than during the initial ascending phase. 相似文献
6.
Maurice Meseke Jan Felix Evers Carsten Duch 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2009,195(5):473-489
During the metamorphosis of the holometabolous insect, Manduca sexta, the postembryonic acquisition of adult specific motor behaviors is accompanied by changes in dendritic architecture, membrane
currents, and input synapses of identified motoneurons. This study aims to test whether increased activity affects dendritic
architecture and sub-dendritic input synapse distribution of the identified flight motoneuron 5 (MN5). Systemic injections
of the chloride channel blocker, picrotoxin (PTX), during early pupal stages increase pupal reflex responsiveness, but overall
development is not impaired. MN5 input resistance, resting membrane potential, and spiking threshold are not affected. Bath
application of PTX to isolated ventral nerve cords evokes spiking in pupal and adult flight motoneurons. Quantitative three-dimensional
reconstructions of the dendritic tree of the adult MN5 show that systemic PTX injections into early pupae cause dendritic
overgrowth and reduce the density of GABAergic inputs. In contrast, the distribution patterns of GABAergic terminals throughout
the dendritic tree remain unaltered. This indicates that increased overall excitability might cause dendritic overgrowth and
decreased inhibitory input during postembryonic motoneuron remodeling, whereas sub-dendritic synapse targeting might be controlled
by activity-independent signals. Behavioral testing reveals that these neuronal changes do not impede the animal’s ability
to fly, but impair maximum flight performance. 相似文献
7.
The distribution and morphology of motoneurons innervating specific types of muscle fibers in the levator scapulae superior (LSS) muscle complex of the bullfrog (Rana catesbeiana) and tiger salamander (Ambystoma tigrinum) were studied by retrograde labelling with cholera toxin-conjugated horseradish peroxidase (CT-HRP). The LSS muscle complex in both of these amphibians has a segregated pattern of muscle-fiber types (tonic; fast oxidative-glycolytic twitch [FOG]; fast glycolytic twitch [FG]) along an anteroposterior axis. The entire motor pool was labelled by injection of CT-HRP into the whole LSS muscle complex. The motoneurons innervating specific fiber types were labelled by injection of CT-HRP into certain muscle regions. The organization of the motoneuron pool of the LSS complex of both species was arranged in two columns—one ventrolateral and one medial. In bullfrogs, the ventrolateral column contains motoneurons innervating FG and tonic fiber types and the medial column contains motoneurons innervating FOG fiber types. In tiger salamanders, the ventrolateral column contains motoneurons innervating FG fiber types and the medial column contains motoneurons innervating FOG and tonic fiber types. The different motoneuron types also have different soma sizes and patterns of dendritic arborization. In both species, FG motoneurons are the largest, whereas FOG motoneurons are intermediate in size and tonic motoneurons are the smallest. In bullfrogs, the main dendrites of FG motoneurons extend into the dorsolateral and the ventrolateral gray matter of the spinal cord, whereas the dendrites of FOG motoneurons extend into the ventral and medial cord. In the tiger salamander, dendrites of FG motoneurons extend into the ventrolateral spinal cord and dendrites of the FOG motoneurons extend more generally into the ventral cord. Dendrites of tonic motoneurons in both amphibians were small and short, and difficult to observe. These results establish that motoneurons innervating different types of muscle fibers in the LSS muscle complex are segregated spatially and display consistent morphological differences. © 1993 Wiley-Liss, Inc. 相似文献
8.
Motoneuron loss is a significant medical problem, capable of causing severe movement disorders or even death. We have been investigating the effects of motoneuron loss on surviving motoneurons in a lumbar motor nucleus, the spinal nucleus of the bulbocavernosus (SNB). SNB motoneurons undergo marked dendritic and somal atrophy following the experimentally induced death of other nearby SNB motoneurons. However, treatment with testosterone at the time of lesioning attenuates this atrophy. Because testosterone can be metabolized into the estrogen estradiol (as well as other physiologically active steroid hormones), it was unknown whether the protective effect of testosterone was an androgen effect, an estrogen effect, or both. In the present experiment, we used a retrogradely transported neurotoxin to kill the majority of SNB motoneurons on one side of the spinal cord only in adult male rats. Some animals were also treated with either testosterone, the androgen dihydrotestosterone (which cannot be converted into estradiol), or the estrogen estradiol. As seen previously, partial motoneuron loss led to reductions in soma area and in dendritic length and extent in surviving motoneurons. Testosterone and dihydrotestosterone attenuated these reductions, but estradiol had no protective effect. These results indicate that the neuroprotective effect of testosterone on the morphology of SNB motoneurons following partial motoneuron depletion is an androgen effect rather than an estrogen effect. 相似文献
9.
Chiovini B Turi GF Katona G Kaszás A Erdélyi F Szabó G Monyer H Csákányi A Vizi ES Rózsa B 《Neurochemical research》2010,35(12):2086-2095
In this study two-photon imaging and single cell electrophysiological measurements were carried out in PV+ hippocampal interneurons
to compare the dendritic calcium dynamics of somatically evoked backpropagating action potentials (BAPs) and in vitro sharp
wave oscillation (SPW) activated BAPs at different distances from the soma. In the case of 300 μm thick, non-oscillating slices,
the BAP-evoked Ca2+ (BAP-Ca2+) influx propagated along the dendritic tree in a non-uniform manner and its amplitude gradually reduced when measured at
more distal regions. In contrast to the evoked BAP-Ca2+s, the spontaneous SPW-induced Ca2+ influx had only a small distance-dependent decrement. Our results suggest that similarly to nicotinic acetylcholine receptor
activation, synaptic activity during hippocampal SPWs increases AP backpropagation into distant dendritic segments. Bath application
of Nimodipine, a specific Ca2+ channel blocker and tetrodotoxine decreased the amplitude of the somatically evoked Ca2+ influx, which suggests that L-type Ca2+ channels play an important role both during somatically evoked and SPW-induced BAPs. 相似文献
10.
David H. Jewson Nick G. Granin Andre A. Zhdanov Ruslan Yu Gnatovsky 《Aquatic Ecology》2009,43(3):673-679
Lake Baikal freezes for 4–5 months each year; yet the planktonic diatoms that grow under the ice include some of the largest
species found in freshwater. An important factor influencing their growth is the depth of snow. In this study, a population
of Aulacoseira baicalensis developed where there was little or no snow on the ice but declined where there was 10 cm of snow, because 99% of the available
light was attenuated. Culture studies of light response showed that A. baicalensis was adapted to relatively low light intensities (<40 μmol m−2 s−1) that were close to the average that a cell experiences in L. Baikal when mixed vertically by convection to depths that can
exceed 100 m. On sunny days, cell division could be inhibited down to >10 m depth but narrow (<15 μm) diameter cells trapped
in high light intensities in sub-ice layers switched to auxosporulation and size regeneration. 相似文献
11.
Al-Hussain Bani Hani SM El-Dwairi QA Bataineh ZM Al-Haidari MS Al-Alami J 《Cellular and molecular neurobiology》2008,28(3):411-416
The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in
Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were
medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic
mean diameter of 30.8 μm (±9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean
diameters of their primary, secondary, and tertiary dendrites were 3.1 μm (±1, n = 80), 1.85 μm (±0.8, n = 145), and 1.5 μm (±0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic
stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 μm (±5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean
diameters of their primary, secondary, and tertiary dendrites were 1.6 μm (±0.86, n = 70), 1.15 μm (±0.55, n = 118), and 1 μm (±0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some
degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic
neurons. 相似文献
12.
Three large median cell bodies with a diameter between 40 and 70 μm that exhibit octopamine immunoreactivity were identified in the posterior part of the suboesophageal ganglion of the tobacco hawkmoth larva, Manduca sexta. These neurons possess bilaterally symmetrical axons in the posterior neck connectives, and at least one of them extends through the whole ventral nerve cord to the terminal abdominal ganglion. Therefore, these neurons belong to the class of descending ventral unpaired median neurons. From each cell body, a primary neurite ascends anteriorly, which after bending dorsally turns posteriorly and then bifurcates to give rise to two descending axons. From the primary neurite two main dendritic branches ascend anteriorly, and four characteristic branches can be distinguished originating from them: two descending dendritic branches and two ascending dendritic branches. Dense arborizations from all these branches exist in all neuromeres of the suboesophageal ganglion. Intracellular recordings from these neurons show that in contrast to the ventral unpaired median neurons of thoracic and abdominal ganglia, they do not produce overshooting action potentials but exhibit passive soma spikes only. During pharmacologically evoked fictive motor patterns these neurons show coupling to various motor patterns such as crawling, feeding and molting. 相似文献
13.
Bilsland LG Nirmalananthan N Yip J Greensmith L Duchen MR 《Journal of neurochemistry》2008,107(5):1271-1283
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motoneuron degeneration resulting in paralysis and eventual death. ALS is regarded as a motoneuron-specific disorder but increasing evidence indicates non-neuronal cells play a significant role in disease pathogenesis. Although the precise aetiology of ALS remains unclear, mutations in the superoxide dismutase (SOD1) gene are known to account for approximately 20% of familial ALS. We examined the influence of SOD1(G93A) expression in astrocytes on mitochondrial homeostasis in motoneurons in a primary astrocyte : motoneuron co-culture model. SOD1(G93A) expression in astrocytes induced changes in mitochondrial function of both SOD1(G93A) and wild-type motoneurons. In the presence of SOD1(G93A) astrocytes, mitochondrial redox state of both wild-type and SOD1(G93A) motoneurons was more reduced and mitochondrial membrane potential decreased. While intra-mitochondrial calcium levels [Ca(2+)](m) were elevated in SOD1(G93A) motoneurons, changes in mitochondrial function did not correlate with [Ca(2+)](m). Thus, expression of SOD1(G93A) in astrocytes directly alters mitochondrial function even in embryonic motoneurons, irrespective of genotype. These early deficits in mitochondrial function induced by surrounding astrocytes may increase the vulnerability of motoneurons to other neurotoxic mechanisms involved in ALS pathogenesis. 相似文献
14.
Maria Meyer Maria Claudia Gonzalez Deniselle Laura I. Garay Gisella Gargiulo Monachelli Analia Lima Paulina Roig Rachida Guennoun Michael Schumacher Alejandro F. De Nicola 《Cellular and molecular neurobiology》2010,30(1):123-135
In the Wobbler mouse, a mutation in the Vps54 gene is accompanied by motoneuron degeneration and astrogliosis in the cervical
spinal cord. Previous work has shown that these abnormalities are greatly attenuated by progesterone treatment of clinically
afflicted Wobblers. However, whether progesterone is effective at all disease stages has not yet been tested. The present
work used genotyped (wr/wr) Wobbler mice at three periods of the disease: early progressive (1–2 months), established (5–8 months)
or late stages (12 months) and age-matched wildtype controls (NFR/NFR), half of which were implanted with a progesterone pellet
(20 mg) for 18 days. In untreated Wobblers, degenerating vacuolated motoneurons were initially abundant, experienced a slight
reduction at the established stage and dramatically diminished during the late period. In motoneurons, the cholinergic marker
choline acetyltransferase (ChAT) was reduced at all stages of the Wobbler disease, whereas hyperexpression of the growth-associated
protein (GAP43) mRNA preferentially occurred at the early progressive and established stages. Progesterone therapy significantly
reduced motoneuron vacuolation, enhanced ChAT immunoreactive perikarya and reduced the hyperexpression of GAP43 during the
early progressive and established stages. At all stage periods, untreated Wobblers showed high density of glial fibrillary
acidic protein (GFAP)+ astrocytes and decreased number of glutamine synthase (GS) immunostained cells. Progesterone treatment
down-regulated GFAP+ astrocytes and up-regulated GS+ cell number. These data reinforced the usefulness of progesterone to
improve motoneuron and glial cell abnormalities of Wobbler mice and further showed that therapeutic benefit seems more effective
at the early progressive and established periods, rather than on advance stages of spinal cord neurodegeneration. 相似文献
15.
The efficacy of excitation induced by iontophoretic application of excitatory amino acids to the soma or different parts of the dendritic tree has been compared in experiments performed on parietal cortex slices. Spike activity was recorded extracellularly from single nerve cells of layer V. In total, the responses of 125 neurons were analyzed. Upon application of glutamate and aspartate to the neuronal soma and the majority of dendrites, latencies of excitatory responses did not exceed 500 msec. In 18% of cases, neuronal responses to transmitter application to basal and apical dendrites had longer (2–3 sec) latencies. The maximum intensity of responses was observed when excitatory amino acids had been applied to the soma or proximal parts of dendrites. If applied at a distance of over 100 µm to basal and 300 µm to apical dendrites, glutamate and aspartate elicited cellular responses whose intensity was 2–3 times lower than that of the responses induced by application to the soma. The maximum distances at which somatic spike responses could be recorded were 350 µm and 800 µm for basal and apical dendrites, respectively. Different latencies of the responses to somatic and dendritic applications of excitatory amino acids in some neurons, as well as high efficacy of responses to stimulation of remote parts of dendritic tree, may indicate nonidentity of electrical properties of dendritic and somatic membranes.Neirofiziologiya/Neurophysiology, Vol. 25, No. 6, pp. 437–446, November–December, 1993. 相似文献
16.
The effect of extracellularly applied electrical fields on neuronal excitability and firing behavior is attributed to the interaction between neuronal morphology and the spatial distribution and level of differential polarization induced by the applied field in different elements of the neuron. The presence of voltage-gated ion channels that mediate persistent inward currents (PICs) on the dendrites of spinal motoneurons enhances the influence of electrical fields on the motoneuronal firing behavior. The goal of the present study was to investigate, with a realistic motoneuron computer model, the effects of extracellularly applied electrical fields on the excitability of spinal motoneurons with the aim of reducing the increased motoneuronal excitability after spinal cord injury (SCI). Our results suggest that electrical fields could suppress the excitability of motoneurons and reduce their firing rate significantly by modulating the magnitude of their dendritic PIC. This effect was achieved at different field directions, intensities, and polarities. The reduction in motoneuronal firing rate resulted from the reduction in the magnitude of the dendritic PIC reaching the soma by the effect of the applied electrical field. This reduction in PIC was attributed to the dendritic field-induced differential polarization and the nonlinear current-voltage relationship of the dendritic PIC-mediating channels. Because of the location of the motoneuronal somata and initial segment with respect to the dendrites, these structures were minimally polarized by the applied field compared with the extended dendrites. In conclusion, electrical fields could be used for suppressing the hyperexcitability of spinal motoneurons after SCI and reducing the level of spasticity. 相似文献
17.
Feral white-footed mice are seasonal breeders that undergo predictable cycles of reproductive function. Photoperiod-induced fluctuations in gonadal function of white-footed mice were associated with morphological changes in perineal muscles and their motoneurons. Exposure to short daylengths resulted in testicular regression, decreased perineal muscle mass, and shrinkage of somata and nuclei of motoneurons of the spinal nucleus of the bulbocavernosus (SNB). These effects were reversed by reinstatement of long daylengths. Similar reductions in muscle mass and SNB soma size were seen following gonadectomy of white-footed mice. In addition, dendritic trees of SNB motoneurons were reduced in gonadectomized mice compared with dendritic arbors of intact mice or castrates provided with testosterone capsules. Androgen-mediated annual changes in muscle mass and motoneuron morphology appear to be a natural part of this species' physiology. 相似文献
18.
Michael A. Pfaller Daniel J. Diekema Mariana Castanheira Ronald N. Jones 《Current fungal infection reports》2011,5(3):120-127
Antifungal susceptibility testing of Candida against the echinocandin antifungal agents (anidulafungin [ANF], caspofungin [CSF], micafungin [MCF]) has been standardized
by the Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antifungal Testing. The CLSI proposed a single set
of clinical breakpoints (CBPs) for all three echinocandins and all species of Candida: susceptible, minimum inhibitory concentration (MIC) ≤ 2 μg/mL; nonsusceptible, MIC > 2 μg/mL. Subsequently, these CBPs have
been shown to lack sensitivity in detecting strains of Candida with acquired resistance mechanisms associated with treatment failure. Studies using the CLSI method have defined wild-type
(WT) MIC distributions and epidemiologic cutoff values (ECVs) for each echinocandin and the common species of Candida. The ECVs serve as a sensitive means of discriminating WT strains from those with acquired resistance mechanisms. WT MIC
distributions revealed ECV ranges of 0.03 to 0.25 μg/mL for all major species except C. parapsilosis (1–4 μg/mL) and C. guilliermondii (4–16 μg/mL). These ECVs reliably differentiate WT strains of each species from non-WT strains containing fks mutations. These data, coupled with additional biochemical, clinical, pharmacokinetic, and pharmacodynamic considerations,
have resulted in new CBPs of ≤0.25 μg/mL (susceptible), 0.5 μg/mL (intermediate), and ≥1 μg/mL (resistant) for ANF, CSF, and
MCF for C. albicans, C. tropicalis, and C. krusei. For these agents and C. parapsilosis, the new CBPs are ≤2 μg/mL (susceptible), 4 μg/mL (intermediate), and ≥8 μg/mL (resistant). For C. glabrata, the CBPs for ANF and CSF are ≤0.12 μg/mL (susceptible), 0.25 μg/mL (intermediate), and ≥0.5 μg/mL (resistant), whereas those
for MCF are ≤0.06 μg/mL, 0.12 μg/mL, and ≥0.25 μg/mL, respectively. Application of both ECVs and the lower species-specific
CBPs for the echinocandins has proven useful in both resistance surveillance and clinical care and will serve as an important
step in international harmonization of in vitro susceptibility testing of this important antifungal class. 相似文献
19.
Hellwig B 《Biological cybernetics》2000,82(2):111-121
This study provides a detailed quantitative estimate for local synaptic connectivity between neocortical pyramidal neurons.
A new way of obtaining such an estimate is presented. In acute slices of the rat visual cortex, four layer 2 and four layer
3 pyramidal neurons were intracellularly injected with biocytin. Axonal and dendritic arborizations were three-dimensionally
reconstructed with the aid of a computer-based camera lucida system. In a computer experiment, pairs of pre- and postsynaptic
neurons were formed and potential synaptic contacts were calculated. For each pair, the calculations were carried out for
a whole range of distances (0 to 500 μm) between the presynaptic and the postsynaptic neuron, in order to estimate cortical
connectivity as a function of the spatial separation of neurons. It was also differentiated whether neurons were situated
in the same or in different cortical layers. The data thus obtained was used to compute connection probabilities, the average
number of contacts between neurons, the frequency of specific numbers of contacts and the total number of contacts a dendritic
tree receives from the surrounding cortical volume. Connection probabilities ranged from 50% to 80% for directly adjacent
neurons and from 0% to 15% for neurons 500 μm apart. In many cases, connections were mediated by one contact only. However,
close neighbors made on average up to 3 contacts with each other. The question as to whether the method employed in this study
yields a realistic estimate of synaptic connectivity is discussed. It is argued that the results can be used as a detailed
blueprint for building artificial neural networks with a cortex-like architecture.
Received: 30 March 1999 / Accepted in revised form: 5 August 1999 相似文献
20.
The larval–pupal transformation of Manduca sexta is accompanied by the loss of the abdominal prolegs. The proleg muscles degenerate, the dendritic arbors of proleg motoneurons regress, and a subset of the proleg motoneurons dies. The regression and death of proleg motoneurons are triggered by the prepupal peak of ecdysteroids in the hemolymph. To investigate the possible involvement of protein synthesis in these events, we gave insects repeated injections of the protein synthesis inhibitor, cycloheximide (CHX), during the prepupal peak. Examination of insects 3–5 days following CHX treatment showed that CHX inhibited the death of proleg motoneurons and the production of pupal cuticle in a dose-dependent fashion. When insects were allowed to survive for 10 days after the final CHX injection, motoneuron death and pupal cuticle production sometimes occurred belatedly, apparently in response to the ecdysteroid rise that normally triggers adult development. CHX treatments that inhibited motoneuron death were less effective in inhibiting dendritic regression in the same neurons. In another set of experiments, abdomens were isolated from the ecdysteroid-secreting glands prior to the prepupal peak, and infused with 20-hydroxyecdysone (20-HE). Single injections of CHX delivered just prior to the start of the 20-HE infusion inhibited motoneuron death and pupal cuticle production, but in the range of doses tested, did not prevent dendritic regression. Our findings suggest that protein synthesis is a required step in the steroid-mediated death of proleg motoneurons, and that dendritic regression is less susceptible to inhibition by CHX than is motoneuron death. © 1993 John Wiley & Sons, Inc. 相似文献