采用共聚焦显微术对家兔呼吸道感受器进行观察

呼吸道感受器在机体对肺部物理和化学环境变化作出反应时起到重要作用,它们引起的反射具有调节或保护作用,或产生病理效应。基于电生理研究,可将呼吸道感受器分为四类,但它们的组织结构不详。由于对感受器形态的认识不足,阻碍了对其生理功能的理解。近来,我们采用共聚焦显微术与免疫组织化学方法（用钠钾ATP酶作为标记),首次高清晰度地展示了呼吸感受器结构。本文采用这种新方法在家兔中进行了系统观察。结果显示,各级气道通均有多种不同的感受器结构。大气道中的结构往往比小气道中的复杂,虽然它们的大小、所在部位与走向不尽相同,但都有多个终端末梢。有些感受器埋置在气道平滑肌中,其结构便于感受对气道的机械性刺激：有些覆盖在气道上皮的表面,其形态适合于感受通过气道的刺激性物质;另一些则位于气道粘膜下,在上皮与平滑肌之间。有些传入神经轴突可支配多个感受器结构。据此,传入单纤维中记录到的电活动是来自一个感觉单位。后者可以由多个感受器组成。除了感受器之外,我们还观察到气道内神经节,它们与感受神经的轴突密切相关。本文证实气道内存在不同形态结构的感受器,并探讨了其生理分类。     

哇巴因刺激肺慢适应感受器

钠钾泵抑制剂——哇巴因能引起气道内慢适应感受器异相发放,表现为冲动在正常时的吸气相发放,呼气相终止转变为在呼气相发放,吸气相终止。我们推测异相发放由过度兴奋所致,如果假设正确,那么降低气道压力从而减少对感受器刺激,将能防止异相发放。本工作在麻醉、开胸、机械通气（在呼气末附加3cm水柱的正压）的家兔中记录颈迷走神经中慢适应感受器的单位放电,向感受野注射微量哇巴因（1μmol／L,20μ1）,可观察到感受器活动发生变化。感受器放电经历紧张性发放、异相发放、以及不规则发放三个时期,随后放电终止,进入静息状态。在紧张期,感受器呈持续发放,冲动频率随肺部通气变化的波动幅度明显减小。在异相发放期,感受器活动出现突然发放（呼气相）与终止（吸气相）,其冲动快速转换于高频发放和静止之间。此时,若撤除呼气末正压而减少气道内压力,感受器活动恢复正常,即冲动频率于气管压峰值时为最高,在呼气相减少或终止。在不规则期,感受器通常处于静止状态,时而出现突发高频冲动,且与呼吸周期无关。可以设想：在吸气相,感受器受到牵拉,引起钠、钙等阳离子内流,产生感受器电位。正常时,由于激活钠泵,将钠离子泵出细胞,使感受器电位回复。当钠泵受到抑制后,钠外流受阻,感受器电位加大。在异相发放期,肺充气时牵拉感受器,进一步增加感受器电位,当它超越了产生动作电位的活动范围后,则感受器因过度去极化而失去兴奋性。     

细有髓鞘神经纤维(Aδ)背根反射的观察

背根反射(DRR)反映了初级传入纤维的突触前抑制。本文作者用剥制腓肠神经或背根的神经细束记录单位放电的方法观察 Aδ纤维 DRR,揭示了一些以前用记录复合动作电位的方法所未能观察到的现象。多数 Aδ单位的 DRR 为重复放电。放电数2—4个,经多次刺激后有些单位可达5—6个。放电持续时间为2—9毫秒,个別单位可达13毫秒。每隔2秒钟给予一次电刺激,每次刺激皆可引起 Aδ纤维 DRR。通常 Aα-β纤维的传入冲动即足以引起 Aδ纤维 DRR。大约有20%的 Aδ纤维 DRR 必须要同时有 Aδ纤维的传入冲动才能产生。在双电脉冲刺激测试中第一个刺激引起的 Aδ纤维 DRR 对后一个刺激引起的 DRR 有长达数百毫秒的抑制作用。当两个刺激相隔5毫秒时,我们观察不到象文献中用记录复合动作电位的方法所观察到的加强作用。重复电刺激传入神经对 Aδ纤维 DRR 有长时间的后抑制效应。Aδ纤维 DRR 的脊髓内延搁时间变动范围较大,最小为3.6毫秒,大多数单位为4—6毫秒,也有长达26毫秒的。     

在自发呼吸时肺回缩引起的迷走神经传入放电

本文在麻醉的兔、猫、猴三种动物剥制颈迷走神经纤维细束,并记录其放电。看到有一部分迷走传入纤维放电与自发呼吸的呼气相同步。用切断腹腔迷走支和返喉神经,向食道注气或抽气、人工气胸等方法证明这种传入放电来自肺部的感受器。肺回缩极易使之兴奋,肺充气则不易兴奋之。其适应性慢,纤维传导速度中等。作者设想这种感受器和肺牵张感受器一起组成“成对感受器”,认为这有利于动物对呼吸的深度和频率进行调节。     

针刺或压迫引起的肌肉神经无髓鞘纤维传入放电的观察

以前,我们曾经在猫的胫前肌神经有髓鞘纤维(简称A纤维)上记录牵张感受器和深部压力感受器(即A压力感受器)的单位传入放电。根据A压力感受器对针刺刺激的电反应特性及其感受野的分布,我们推想它们参与针刺期间“针感”的形成并起着镇痛作用(魏仁榆等,1973)。现已知道,在猫的肌肉神经中,无髓鞘传入纤维(简称C纤维)比A纤维多一倍(Stacey,1969),但对它们的生理功能目前了解得不多(Matthews,1972;Iggo,1961;Meuse等,1974)。它们对针刺刺激的反应特性也未见有报告。我们曾试图用相关分析的     

用荧光标记钠钾ATP酶显示气道感受器结构

由于普通光学和荧光显微镜功能上的限制以及缺乏良好的染色方法,我们对于呼吸道感受器形态方面的认识进展缓慢,缺乏对感受器结构的认识,阻碍了对其基本生理活动的探讨,随着共聚焦显微镜的产生与图像处理技术的进展,不但提高了对荧光结构的分辨率,还可通过三维重组而展现微小物体的整体结构。本文阐述了一种新颖方法,利用上述技术并结合免疫组织化学方法,采用Na^ /K^ -ATPase作为标记,对家兔呼吸道感受器进行了观察。本文中经过处理的气道组织结构,背景清晰,感受器部位着色强,观察到的整个感受器,结构复杂,呈树枝状,感受器末梢膨大,形成叶片状,本文首次以高清晰度展示了呼吸气道中单个感受器的整体结构,改变了需要以手绘来刻画感受器的现状,无疑,这种新方法能促进了解感受器的结构及其生理活动的机理。     

吗啡抑制福氏佐剂致炎大鼠触诱发痛的机制

目的:观察吗啡对炎性大鼠触诱发痛的作用并进一步探讨其机制.方法:应用电生理技术记录后二头半腱(PBST)肌肌电及胫神经A、C类纤维单位放电.结果:静脉注射吗啡(1 mg/kg)能明显抑制大鼠炎症侧PBST肌伤害性屈肌反射,此作用可被纳洛酮(1 mg/kg)阻断;相同剂量的吗啡对来自炎症脚趾的胫神经A类纤维自发放电无影响,但却可明显抑制相同侧C类纤维的自发放电.结论:吗啡抑制炎性大鼠触诱发痛,此作用是通过中枢神经系统而非通过外周神经系统实现.     

电刺激大鼠脊神经皮支对远距离机械感受单位电活动的影响

实验采用分离神经细束的方法,观察逆行电刺激大鼠脊神经背侧皮支后,在相距较远的神经细束上记录到的Aδ和C类机械感受单位电活动的变化。刺激T9脊神经背侧皮支,在T12神经细束上记录到59.3%（16/27）的Aδ和71.2%(37/52）的C类单位在刺激后90～120s放电显著增加。刺激T8脊神经背侧皮支,在T12神经细束上记录到47.8%(11/23）的Aδ单位和36.6%(15/41）的C类单位在刺激后120～150s放电显著增加。大多数单位（18/23）的机械感受阈值在电刺激远距离脊神经背侧皮支后降低。结果表明,逆行电刺激外周感觉神经,可以使相距较远的Aδ和C类机械感受单位致敏,其传入放电增加。     

一氧化氮对家兔压力感受器活动的影响

本实验旨在研究外源性一氧化氮对家兔离体颈动脉窦压力感受器活动的影响,进一步探讨这种影响是否由ｃＧＭＰ所介导。实验中发现：（１）窦神经传入纤维基础放电大致可分为高幅值和低幅值两种,其中高幅值放电对经典的化学感受性刺激无反应并呈现显著的灌流速度依赖性。这些放电特征证明其不是来自于颈动脉体化学感受器而是来自ＣＳ－ＢＲ。（２）ＮＯ的前体Ｌ－精氨酸（４．６￣５．７ｎｍｏｌ／Ｌ）和供体硝酸甘油（０．０７￣０．     

电刺激大鼠腓肠神经引起Aδ、 C类传入神经纤维的背根反射

在距脊髓约 15mm处切断大鼠L5背根 ,将中枢端分成 4～ 5条细束 ,电刺激腓肠神经在背根细束上记录背根反射 (dorsalrootreflex ,DRR)。共记录到DRR 5 1例 ,根据引起DRR所兴奋的腓肠神经纤维类别和DRR在背根逆向传出的纤维类别将DRR分为 5类 :Aαβ Aαβ·DRR、Aβδ Aδ·DRR、Aβδ C·DRR、Aαβδδ C·DRR和C C·DRR。结果证明 ,电刺激外周神经激活各类纤维不但能引起A类 (包括Aδ)纤维的DRR ,而且也能引起C类纤维的DRR。记录的Aδ·DRR和C·DRR为细纤维传入终末产生突触前抑制提供了客观指标 ,为DRR逆向传出冲动到达外周组织 ,释放神经肽类递质 ,调节外周效应器的功能提供了证据     

Testing the efficiency of sensory coding with optimal stimulus ensembles

According to Barlow's seminal "efficient coding hypothesis," the coding strategy of sensory neurons should be matched to the statistics of stimuli that occur in an animal's natural habitat. Using an automatic search technique, we here test this hypothesis and identify stimulus ensembles that sensory neurons are optimized for. Focusing on grasshopper auditory receptor neurons, we find that their optimal stimulus ensembles differ from the natural environment, but largely overlap with a behaviorally important sub-ensemble of the natural sounds. This indicates that the receptors are optimized for peak rather than average performance. More generally, our results suggest that the coding strategies of sensory neurons are heavily influenced by differences in behavioral relevance among natural stimuli.     

Sparsity and Compressed Coding in Sensory Systems

Considering that many natural stimuli are sparse, can a sensory system evolve to take advantage of this sparsity? We explore this question and show that significant downstream reductions in the numbers of neurons transmitting stimuli observed in early sensory pathways might be a consequence of this sparsity. First, we model an early sensory pathway using an idealized neuronal network comprised of receptors and downstream sensory neurons. Then, by revealing a linear structure intrinsic to neuronal network dynamics, our work points to a potential mechanism for transmitting sparse stimuli, related to compressed-sensing (CS) type data acquisition. Through simulation, we examine the characteristics of networks that are optimal in sparsity encoding, and the impact of localized receptive fields beyond conventional CS theory. The results of this work suggest a new network framework of signal sparsity, freeing the notion from any dependence on specific component-space representations. We expect our CS network mechanism to provide guidance for studying sparse stimulus transmission along realistic sensory pathways as well as engineering network designs that utilize sparsity encoding.     

Separation of factors responsible for change in breathing pattern induced by instrumentation

Employment of mouthpiece and noseclips (MP + NC) has repeatedly been shown to increase tidal volume (VT), but its effect on respiratory frequency (f) and its subsets is controversial. The mechanisms accounting for this alteration in breathing pattern are poorly understood and may include stimulation of oral or nasal sensory receptors or alteration in the route of breathing. In this study we demonstrated that use of a MP + NC, compared with nonobtrusive measurement with a calibrated respiratory inductive plethysmograph, alters the majority of the volume and time indexes of breathing pattern, with increases in minute ventilation (P less than 0.01), VT (P less than 0.001), inspiratory time (TI, P less than 0.05), expiratory time (TE, P less than 0.05), mean inspiratory flow (P less than 0.05), and mean expiratory flow (P less than 0.05) and a decrease in f(P less than 0.05). Separating the potential mechanisms we found that when the respiratory route was not altered, independent oral stimulation (using an occluded MP) or nasal stimulation (by applying paper clips to the alae nasi) did not change the breathing pattern. In contrast, obligatory oral breathing without additional stimulation of the oral or nasal sensory receptors caused increases in VT (P less than 0.05), TI (P less than 0.05), and TE (P less than 0.01) and a fall in f(P less than 0.05). Heating and humidifying the inspired air did not prevent the alteration in breathing pattern with a MP. Thus change in the respiratory route is the major determinant of the alteration in breathing pattern with a MP + NC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of inspired air temperature on genioglossus activity during nose breathing in awake humans

Experimental data suggest the presence of sensory receptors specific to the nasopharynx that may reflexly influence respiratory activity. To investigate the effects of inspired air temperature on upper airway dilator muscle activity during nose breathing, we compared phasic genioglossus electromyograms (EMGgg) in eight normal awake adults breathing cold dry or warm humidified air through the nose. EMGgg was measured with peroral bipolar electrodes during successive trials of cold air (less than or equal to 15 degrees C) and warm air (greater than or equal to 34 degrees C) nasal breathing and quantified for each condition as percent activity at baseline (room temperature). In four of the subjects, the protocol was repeated after topical nasal anesthesia. For all eight subjects, mean EMGgg was greater during cold air breathing than during baseline (P less than 0.005) or warm air breathing (P less than 0.01); mean EMGgg during warm air breathing was not significantly changed from baseline. Nasal anesthesia significantly decreased the mean EMGgg response to cold air breathing. Nasal airway inspiratory resistance, measured by posterior rhinomanometry in six subjects under similar conditions, was no different for cold or warm air nose breathing [cold 1.4 +/- 0.7 vs. warm 1.4 +/- 1.1 (SD) cmH2O.l-1.s at 0.4 l/s flow]. These data suggest the presence of superficially located nasal cold receptors that may reflexly influence upper airway dilating muscle activity independently of pressure changes in awake normal humans.     

Tracheobronchial muscle tonus and its reflex control

Airway smooth muscle tone is reinforced during the inspiratory phase of the breathing cycle and depends largely from neurogenic motor drive carried by the vagus nerve. This muscle tone seems to be produced mostly by a vago-vagal reflex loop initiated by the tonic discharge of tracheo-bronchial and/or alveolar receptors connected to thin sensory vagal fibres (non-myelinated or C-fibres). Inhibitory influences carried by large myelinated vagal fibres connected to tracheobronchial stretch receptors and also numerous afferents from the upper airways, systemic and pulmonary circulation, digestive tract and skeletal and respiratory muscles participate to the modulation of airway tone. The identification of neurotransmitters specific of the motor or sensory pathways helps to understand the peripheral modulation of airway motor drive and also the central integration of some peripheral informations.     

Integrating spatial structure and interspecific and intraspecific plant–soil feedback effects and responses into community structure

Plant–soil feedbacks have important effects on plant communities, but most theory has been derived from experiments on intraspecific plant–soil feedbacks. Much less is known about how interspecific plant–soil feedbacks affect coexistence and plant communities, due in part to experimental and analytical challenges. Here, we propose a framework for evaluating plant–soil feedbacks among multiple interacting species that incorporates 1) the average effect each species has on conspecific and heterospecific neighbors via how they modify soil biota, 2) the average response of each species to the soil modifications made by neighboring species, and 3) intraspecific feedback. We refer to this as the ‘effect–response–intraspecific’ (ERI) model. We used individual‐based models to evaluate the relative importance of intraspecific and interspecific soil feedback in determining species abundance ranks in simulated plant communities. To compare the heuristic value of the ERI model to that of an established model in which effects and responses to soil feedback are not explicitly recognized, we evaluated a ‘full‐factorial’ model in which soil feedbacks among five plant species were measured and then explicitly modeled. The ERI model indicated that the response to interspecific plant–soil feedbacks was the key factor for species’ abundance rank without spatial structure. In contrast, interspecific plant–soil feedback had no impact on species abundance with spatial structure, and intraspecific feedback became dominant. Thus, our models predict that the relative importance of intraspecific and interspecific feedbacks changes as a function of the degree of spatial structure in a system. Overall, the ERI model provides a novel and tractable framework for evaluating complex multi‐species plant–soil feedbacks.     

The fundamental role of ecological feedback mechanisms for the adaptive management of seagrass ecosystems – a review

Seagrass meadows are vital ecosystems in coastal zones worldwide, but are also under global threat. One of the major hurdles restricting the success of seagrass conservation and restoration is our limited understanding of ecological feedback mechanisms. In these ecosystems, multiple, self‐reinforcing feedbacks can undermine conservation efforts by masking environmental impacts until the decline is precipitous, or alternatively they can inhibit seagrass recovery in spite of restoration efforts. However, no clear framework yet exists for identifying or dealing with feedbacks to improve the management of seagrass ecosystems. Here we review the causes and consequences of multiple feedbacks between seagrass and biotic and/or abiotic processes. We demonstrate how feedbacks have the potential to impose or reinforce regimes of either seagrass dominance or unvegetated substrate, and how the strength and importance of these feedbacks vary across environmental gradients. Although a myriad of feedbacks have now been identified, the co‐occurrence and likely interaction among feedbacks has largely been overlooked to date due to difficulties in analysis and detection. Here we take a fundamental step forward by modelling the interactions among two distinct above‐ and belowground feedbacks to demonstrate that interacting feedbacks are likely to be important for ecosystem resilience. On this basis, we propose a five‐step adaptive management plan to address feedback dynamics for effective conservation and restoration strategies. The management plan provides guidance to aid in the identification and prioritisation of likely feedbacks in different seagrass ecosystems.     

External thoracic restriction, respiratory sensation, and ventilation during exercise in men.

Multiple factors may contribute to the dyspnea associated with restrictive ventilatory disease (RVD). Simple models that examine specific features of this problem are likely to provide insight into the mechanisms. Previous models of RVD utilizing elastic loads may not represent completely the impact on pulmonary and chest wall receptors derived from breathing at low thoracic volumes. The purpose of this study was to investigate the sensory consequences of breathing at low lung volumes induced by external thoracic restriction in an attempt to further elucidate the etiology of dyspnea in this setting. Ten men were studied, with and without an inelastic corset applied at residual volume (restriction resulted in mean reductions in vital capacity, functional residual capacity, residual volume, and forced expired volume in 1 s of 44, 31, 12.5, and 42%, respectively). During 10-min steady-state exercise tests (at a workload set to achieve approximately 65% maximum heart rate), restriction resulted in significant increases, compared with control, in minute ventilation (61 vs. 49 l/min), respiratory frequency (43 vs. 23 breaths/min), and visual analog scale measurements of respiratory discomfort (65 vs. 20 mm). Alveolar hyperventilation (end-tidal PCO2 = 39 vs. 44 Torr for control) and mild O2 desaturation (arterial blood O2 saturation = 93 vs. 95% for control) occurred. Hypoxemia, atelectasis, increased work and effort of breathing, or a decrease in the volume-related feedback from chest wall and/or lungs could be responsible for the increased dyspnea reported. External thoracic restriction provides a useful model to study mechanisms of dyspnea in RVD.     

The contribution of sensory inputs to the pattern generation of breathing

Current concepts of the basic neural control system and its modulation by afferent inputs are reviewed. It is emphasized that, in analogy with locomotion, the central pattern generator (CPG) for automatic metabolic respiration does not depend on any afferent feedback from receptors sensitive to the movements of the "pump," or the streams of pumped air, for its production of a rhythmic motor output provides the CPG receives some "drive" inputs above threshold and adequate bias. The operation for a variety of reflexes and feedback loops is of fundamental importance, however, for adapting the breathing pattern to the varying requirements for gas exchange to the many behavioural, nonmetabolic demands on the breathing apparatus which are competing with its primary metabolic control functions. The presentation is focussed also on available evidence that the respiratory CPG exerts powerful modulations on the transmission in these reflex pathways controlling the pattern of breathing and adjusting it to the various metabolic and behavioural demands. Mechanisms for "gating," "phasic gain changes," and "phase-dependent reflex reversal" are exemplified.