Differential development of TRPV1-expressing sensory nerves in peripheral organs

In mouse ontogeny, neurons immunoreactive for transient receptor potential vanilloid receptor 1 (TRPV1) were observed primarily in the dorsal root ganglia (DRG) at embryonic day 13 (E13). In the embryonic period, the number of TRPV1⁺ neurons decreased, but then gradually increased postnatally. Some of TRPV1⁺ neurons were also immunoreactive for calcitonin gene-related peptide (CGRP). At postnatal day 7 (P7), 66% of CGRP⁺ neurons were TRPV1⁺, and 55% of TRPV1⁺ neurons were also CGRP⁺ in the L4 DRG. In the peripheral organs, TRPV1-immunorective nerve fibers were transiently observed in the skin at E14. They were also observed in the urinary tract at E14, and in the rectum at E15. Many TRPV1⁺ nerve fibers in these organs were also CGRP⁺. At P1, TRPV1⁺ nerve fibers were observed in the respiratory organs, and to a lesser extent in the stomach, colon, skin, and skeletal muscles. The number of TRPV1⁺ nerve fibers on each organ gradually increased postnatally. At P7, TRPV1⁺ nerve fibers were also observed in the small intestine and kidneys. The percentage of total TRPV1⁺ nerve fibers that co-localized with CGRP was greater in most organs at P7 than at P1. The present results indicate that TRPV1 expression on peripheral processes differs among organs. The differential time course of TRPV1 expression in the cell bodies might be related to the organs to which they project. Co-localization of TRPV1 with CGRP on nerve fibers also varies among organs. This suggests that the TRPV1-mediated neuropeptide release that occurs in certain pathophysiologic conditions also varies among organs.     

Trophic interactions between sensory nerves and their targets

Neurotrophins are target-derived trophic factors essential for the survival and maintenance of neurons. Among these, nerve growth factor (NGF) and neurotrophin-3 (NT-3) are particularly important for sensory neurons. The actions of neurotrophins are through the p75 low-affinity receptor and the high-affinity receptor tyrosine kinase(trk). Each neurotrophin has its preferred receptor, i.e.trkA for NGF, andtrkC for NT-3. The primary sensory neurons in the dorsal root ganglion are classified into two categories, namely, the large and small sensory neurons based on their size. The large sensory neurons with the expression oftrkC depend on NT-3 for development and subserve the function of position sensations. Some of the small sensory neurons expresstrkA and are NGF-dependent. They are responsible for nociceptive sensation, the detection of painful and thermal stimuli. A more intriguing observation is the bidirectional interactions between nociceptive nerves and their target, the skin. The peripheral processes of small sensory neurons innervate the epidermis of the skin as free nerve endings. In denervated skin, there is a drastic reduction in the epidermal thickness, a finding corroborated by the phenomenon of trophic change, the shining and thinning of the skin, in the disorders of peripheral nerves. The performance of animals with peripheral nerve disorders improved after administration of neurotrophic factors. Based on these results, the therapeutic potentials of neurotrophic factors in human are under investigation.     

Characterization and modeling of P-type electrosensory afferent responses to amplitude modulations in a wave-type electric fish

The first stage of information processing in the electrosensory system involves the encoding of local changes in transdermal potential into trains of action potentials in primary electrosensory afferent nerve fibers. To develop a quantitative model of this encoding process for P-type (probability-coding) afferent fibers in the weakly electric fish Apteronotus leptorhynchus, we recorded single unit activity from electrosensory afferent axons in the posterior branch of the anterior lateral line nerve and analyzed responses to electronically generated sinusoidal amplitude modulations of the local transdermal potential. Over a range of AM frequencies from 0.1 to 200 Hz, the modulation transfer function of P-type afferents is high-pass in character, with a gain that increases monotonically up to AM frequencies of 100 Hz where it begins to roll off, and a phase advance with a range of 15–60 degrees. Based on quantitative analysis of the observed gain and phase characteristics, we present a computationally efficient model of P-type afferent response dynamics which accurately characterizes changes in afferent firing rate in response to amplitude modulations of the fish's own electric organ discharge over a wide range of AM frequencies relevant to active electrolocation. Accepted: 14 June 1997     

The sensory dorsal organ of crustaceans: Theme and variations

This report presents the results of a scanning electron microscope survey of sensory dorsal organs across a wide range of crustaceans. Sensory dorsal organs are widespread amongst the Crustacea but not ubiquitous. Although many of the organisms surveyed are only distantly related phylogenetically and there is some variation in the appearance of their sensory dorsal organs, a cluster of elements are all or nearly all present. This suggests not only that the sensory dorsal organ appeared very early in crustacean evolution, but that its function requires the elements to be retained in a relatively conservative manner.     

Dye-filling of the amphid sheath glia: implications for the functional relationship between sensory neurons and glia in Caenorhabditis elegans

The nervous system is composed of cells including neurons and glia. It has been believed that the former cells play central roles in various neural functions while the latter ones have only supportive functions for neurons. However, recent findings suggest that glial cells actively participate in neural activities, and the cooperation between neurons and glia is important for nervous system functions. In Caenorhabditis elegans, amphid sensory organs in the head also consist of sensory neurons and glia-like support cells (amphid socket and amphid sheath cells). Ciliary endings of some sensory neurons exposed to the environment detect various chemicals, molecules and signals, and the cilia of some neurons can also take up fluorescent dyes such as DiI. Here, we show that the amphid sheath glia are also stained with DiI and that its uptake by the amphid sheath cells correlates with DiI-filling of sensory neurons, suggesting that the amphid sheath glia might interact with sensory neurons. Furthermore, the localization of the amphid sheath cell reporter F52E1.2SP::YFP is abnormal in che-2 mutants, which have defective cilia. These findings imply that sensory neurons might affect amphid sheath glia functions in the amphid sensory organ of C. elegans.     

Bump amplitude,but not latency and time-course,can depend on position of illumination in Limulus photoreceptor cells

Bumps, the responses evoked by single photons in the ventral photoreceptor of Limulus polyphemus, were measured under voltage clamp conditions. The bumps were evoked by illuminating the photoreceptor either with a global flash or a small light spot (diameter about 5 m) which covers only 0.25% of the light-sensitive part of the cell membrane. The light energy of both flash types was adjusted so that each flash on average evoked one bump. Parameters of bumps evoked by local light spots in various membrane areas were compared with those evoked by light flashes which illuminated the whole photoreceptor. The results show that the bump amplitude depends on the location of the illumination. Membrane areas were found where the average value of the bump amplitude was either smaller or larger for a spot illumination than for a whole cell illumination. The latency and the shape (e.g. width) of the bumps does not depend on the location of the illumination.     

Distribution of sensory neurones of the pudendal nerve in the dorsal root ganglia and their projection to the spinal cord

Summary The morphology and distribution of the sensory neurones of the pudendal nerve within the spinal ganglia of rats were investigated by use of horseradish peroxidase (HRP). The labelling was visualized in diaminobenzidine (DAB) or tetramethyl-benzidine (TMB)-stained sections. Injection of HRP directly into the pudendal nerve labelled perikarya predominantly in the sixth lumbar DRG (L6). Following injection of HRP into the scrotal skin, however, additional cells were labelled in L5 and SI. Labelling was invariably unilateral. Approximately equal numbers of small (<30 m) and large neurones (>40 m) were labelled following subcutaneous injections although injections into the nerve marked twice as many small cells as large cells. This suggests that, in the rat, most of the small-diameter fibres within the pudendal nerve ascend through L6. Although a cluster of neurones was observed in one experiment, the remaining 25 experiments did not reveal any somatotopic arrangement since the labelled perikarya were distributed evenly throughout the ganglion. Similar numbers of retrogradely labelled neurones (somatopetal transport of the tracer) were observed in both DAB- and TMB-stained sections, although TMB allowed the demonstration of anterograde (somatofugal) HRP transport by terminal labelling in the superficial laminae of the lumbar spinal cord, extending into laminae II–IV.Partially supported by grants from the DFG to HWK (Ko 758/1)     

The switch between EBV latency and replication

This paper reviews experiments done in the author's laboratory which led to the discovery of an Epstein-Barr virus (EBV) gene, BZLF1, whose product, ZEBRA, switches the virus from latency to the replicative phase of its life cycle. Recent experiments are summarized which explore the effects of EBV genome rearrangements and cell background on the expression of ZEBRA, and which investigate the viral targets of ZEBRA action.     

Differences in sensory projections between macro- and microchaetes in Drosophilid flies

From examination of the central axonal projections of sensory bristles on the notum of several species of Drosophilidae, we demonstrate different features that may indicate different functions for macro- and microchaetes. The large macrochaetes have conserved arborizations that correlate with their conserved position. Nevertheless, we find evidence for only two discrete projection patterns for bristles in the dorsocentral (DC) row, even when there may be four or five bristles present. We show that the small microchaetes of Drosophila melanogaster display regional specificity and subsets of contiguous bristles project to a common region in the thoracic ganglion. Interestingly, the axons of each of these subsets also form a specific fasciculation group on the scutum before joining the axon of a particular macrochaete. The positions of microchaetes on the scutum and the shape of the fasciculation groups vary between closely related species. There is no correlation between body size, bristle patterns, and fasciculation patterns. Furthermore, none of these traits correlate with the phylogenetic relationships between the species studied. We discuss the possibility that macro- and microchaetes may have different functions and that these have implications for evolutionary constraints on bristle patterns.     

Relationship between amplitude and latency in human monosynaptic reflexes. II. H and M responses]

Relationship between amplitude and latency of H reflex and M response were studied in normal man by recruitment method and Jendrassik manoeuvre. An increase of amplitude was accompanied by a decrease of latency in both responses. This effect was chiefly ascribed to a larger recruitment of muscle fibres.     

Synaptic connections between sensory afferents and the common inhibitory motoneuron in crayfish

The sensory inputs to the common inhibitory motoneuron that innervates every leg muscle of the crayfish Procambarus clarkii (Girard) were analyzed by performing intracellular recordings from its neurite within the neuropil of the 5th thoracic ganglion. Two types of sensory inputs involved in locomotion were studied, those from a movement coding proprioceptor (the coxobasal chordotonal organ) and those from sensory neu rons coding contact forces exerted at the tip of the leg on the substrate (the dactyl sensory afferents). Sinusoidal movements applied to the chordotonal organ strand induced a stable biphasic response in the common inhibitory motoneuron that consisted of bursts of spikes during release and stretch of the strand, corresponding to raising and lowering of the leg, respectively. Using ramp movements imposed on the chordotonal strand, we demonstrated that only movement-coding chordotonal afferents produce excitatory post-synaptic potentials in the common inhibitory motoneuron; these connections are monosynaptic. Mechanical or electrical stimulation of the dactyl sensory afferents resulted in an increase in the tonic discharge of the common inhibitory motoneuron through polysynaptic excitatory pathways. These two types of sensory cues reinforce the central command of the common inhibitory motoneuron and contribute to enhancing its activity during leg movements, and thus facilitate the relaxation of tonic muscle fibres during locomotion.Abbreviations ADR anterior distal root - A Lev anterior levator nerve - CB coxo-basipodite joint - CBCO coxo-basal chordotonal organ - CI common inhibitory motoneuron - Dep depressor nerve - DSA dactyl sensory afferents - EPSP excitatory post-synaptic potential - IN interneuron - MN motoneuron - PDR posterior distal root - P Lev posterior levator nerve - Pro promotor nerve - Rem remotor nerve     

The proteome of rat olfactory sensory cilia

Olfactory sensory neurons expose to the inhaled air chemosensory cilia which bind odorants and operate as transduction organelles. Odorant receptors in the ciliary membrane activate a transduction cascade which uses cAMP and Ca²⁺ for sensory signaling in the ciliary lumen. Although the canonical transduction pathway is well established, molecular components for more complex aspects of sensory transduction, like adaptation, regulation, and termination of the receptor response have not been systematically identified. Moreover, open questions in olfactory physiology include how the cilia exchange solutes with the surrounding mucus, assemble their highly polarized set of proteins, and cope with noxious substances in the ambient air. A specific ciliary proteome would promote research efforts in all of these fields. We have improved a method to detach cilia from rat olfactory sensory neurons and have isolated a preparation specifically enriched in ciliary membrane proteins. Using LC‐ESI‐MS/MS analysis, we identified 377 proteins which constitute the olfactory cilia proteome. These proteins represent a comprehensive data set for olfactory research since more than 80% can be attributed to the characteristic functions of olfactory sensory neurons and their cilia: signal processing, protein targeting, neurogenesis, solute transport, and cytoprotection. Organellar proteomics thus yielded decisive information about the diverse physiological functions of a sensory organelle.     

Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice

Increasing the expression of Hsp70 (heat-shock protein 70) can inhibit sensory neuron degeneration after axotomy. Since the onset of DPN (diabetic peripheral neuropathy) is associated with the gradual decline of sensory neuron function, we evaluated whether increasing Hsp70 was sufficient to improve several indices of neuronal function. Hsp90 is the master regulator of the heat-shock response and its inhibition can up-regulate Hsp70. KU-32 (N-{7-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy]-8-methyl-2-oxo-2H-chromen-3-yl}acetamide) was developed as a novel, novobiocin-based, C-terminal inhibitor of Hsp90 whose ability to increase Hsp70 expression is linked to the presence of an acetamide substitution of the prenylated benzamide moiety of novobiocin. KU-32 protected against glucose-induced death of embryonic DRG (dorsal root ganglia) neurons cultured for 3 days in vitro. Similarly, KU-32 significantly decreased neuregulin 1-induced degeneration of myelinated Schwann cell DRG neuron co-cultures prepared from WT (wild-type) mice. This protection was lost if the co-cultures were prepared from Hsp70.1 and Hsp70.3 KO (knockout) mice. KU-32 is readily bioavailable and was administered once a week for 6 weeks at a dose of 20 mg/kg to WT and Hsp70 KO mice that had been rendered diabetic with streptozotocin for 12 weeks. After 12 weeks of diabetes, both WT and Hsp70 KO mice developed deficits in NCV (nerve conduction velocity) and a sensory hypoalgesia. Although KU-32 did not improve glucose levels, HbA1c (glycated haemoglobin) or insulin levels, it reversed the NCV and sensory deficits in WT but not Hsp70 KO mice. These studies provide the first evidence that targeting molecular chaperones reverses the sensory hypoalgesia associated with DPN.     

感觉再训练及口服弥可保片剂对周围神经修复术后患者感觉功能的影响

目的:探讨感觉再训练及口服弥可保片剂对周围神经修复术后患者感觉功能的影响。方法:选取2009年10月至2011年10月我院收治的腕部损伤患者128例,随机分为A、B、C、D四组,每组各32例,在神经修复术及常规治疗的基础上,D组不采取其他任何措施治疗;C组给予弥可保片剂口服治疗;B组采取感觉再训练治疗;A组采取感觉再训练联合弥可保片剂口服治疗。对比患者术后1年及2年的感觉功能恢复情况及m2-PD检测结果。结果:A、B、C组术后1年及2年的感觉功能分级情况均优于D组,差异有统计学意义(P0.05)。其中,以A组与D组相比,差异最为显著(P0.05)。并且,A组的感觉功能随着时间的延长不断改善。A、B、C组的m2-PD检测结果均优于D组,差异有统计学意义(P0.05)。其中,A组术后1年及2年的检测结果分别为(6.79±2.08)mm、(4.98±2.05)mm,相比于D组的(13.31±1.64)mm、(11.94±2.37)mm,差异最为显著(P0.05);且术后2年的的检测结果明显低于术后1年,差异有统计学意义(P0.05)。结论:将感觉再训练与弥可保口服治疗相结合用于周围神经损伤患者的神经修复术后,治疗效果更佳。能够最大限度的促进患者感觉功能的恢复。     

The relationship between the transition matrix model and the diffusion model

The diffusion equation model and the Lefkovitch matrix model have been employed independently in plant population ecology in order to analyze the dynamics of growth and size structure. The two models describe the dynamics of size structure in biological populations, and thus there must be some relationship between them. In the present paper, we examine the theoretical relationship between these two models. We demonstrate, on a certain assumption, that the one-step Lefkovitch matrix model corresponds to a difference equation of the diffusion equation and that the two- and three-step Lefkovitch matrix model correspond to difference equations of the 4th- and 6th-order Kramers-Moyal expansions, respectively. It is also shown that 2n moments (the first to the 2n-th moments) of growth rate are necessary and sufficient to rewrite uniquely the n-step Lefkovitch matrix model in terms of the linear combination of the moments. We finally discuss the relationship between the species characteristics of census data and the appropriate types of the Lefkovitch matrix.     

The relationship between endophyte transition and plant species coexistence

The survival possibilities of terrestrial plant species are determined by their competitive abilities. One factor that affects competitive ability is the community of microorganisms that lives in association with the plants. Microorganisms affect the competitive dominance among plants by means of their metabolites. In this paper, we study the multiple plant species coexistence mediated by interactions with endophytes (fungi). The population dynamics are described by a revised lottery competition model for multiple plant species, each of which is divided into two classes: plants with endophytes (denoted EP) and plants without endophytes (NEP). The model includes the transition of seeds from EP to NEP. We show multiple species of plants cannot coexist in a steady state if this transition is density independent, but can coexist in a steady state if this transition is an increasing function of population density.     

The relationship between real-time and discrete-generation models of epidemic spread

Many important results in stochastic epidemic modelling are based on the Reed-Frost model or on other similar models that are characterised by unrealistic temporal dynamics. Nevertheless, they can be extended to many other more realistic models thanks to an argument first provided by Ludwig [Final size distributions for epidemics, Math. Biosci. 23 (1975) 33-46], that states that, for a disease leading to permanent immunity after recovery, under suitable conditions, a continuous-time infectious process has the same final size distribution as another more tractable discrete-generation contact process; in other words, the temporal dynamics of the epidemic can be neglected without affecting the final size distribution. Despite the importance of such an argument, its presence behind many results is often not clearly stated or hidden in references to previous results. In this paper, we reanalyse Ludwig’s result, highlighting some of the conditions under which it does not hold and providing a general framework to examine the differences between the continuous-time and the discrete-generation process.     

Ratios between number of neuroglial cells and number and volume of nerve cells in the spinal ganglia of two species of reptiles and three species of mammals

We studied the ratios between number of neuroglial (=satellite) cells and number and volume of neurons with which they are associated in the spinal ganglia of two species of reptiles (lizard and gecko) and three species of mammals (mouse, rat, and rabbit). In all five species, we found that the number of satellite cells associated with a nerve cell body increased with increasing volume of the latter. This result shows that there is a quantitative balance between neuroglia and nerve tissue in spinal ganglia. This balance seems to be maintained by a tight regulation of the number of satellite cells. We also found that the mean volume of nerve cell body corresponding to a satellite cell was lower for small neurons than for large ones. Since satellite cells metabolically support spinal ganglion neurons, the metabolic needs of small neurons are better satisfied than those of large ones. For a nerve cell body of a given size, the number of associated satellite cells did not differ between the lizard and gecko, nor between the mouse, rat, and rabbit. However, this number was significantly smaller in the reptiles than in the mammals. This result could be explained by the lower metabolic rate in the nervous system of poikilotherms than mammals, or could have a phylogenetic significance. These two interpretations are not mutually exclusive.