Sensory Irritation Response in Rats II: Recovery and Dose-Dependence

Inhaled irritants can cause respiratory depression by simulating trigeminal nerves in the nasal cavity. This decrease in inhalation rate results in a decrease in the rate of the irritant gases flowing to the stimulated nerves, creating a complex feedback response. Previously, a model was created to describe how the presence of formaldehyde affects respiration in the rat. This ordinary differential equation model incorporated a model of the physiology of the upper respiratory tract of the rat and a model of the neurological control of the respiration rate due to signaling from the stimulated nerves in the nasal cavity. However, an optimal fit to data was not fully established. In the current study, the fit of the previously established model is reevaluated while incorporating the recovery of the ventilation rate after the end of exposure. Additionally, the dose-dependence of the adaptation time allowed by the previous model is more fully quantified, and the updated model predicts formaldehyde data well. Not only are the results of the previous study improved, the model is also shown to predict ventilation decrease in response to other irritants, specifically acrolein, ammonia, and sulfur dioxide. The model is expected to translate to predictions of other irritants with minor parameter changes.     

Sensory innervation of the tentacles of the polychaete,Sabella pavonina

Summary Following observation of conical groups of stiff, but motile cilia on the tentacles of the branchial crown of Sabella pavonina, these were examined with the electron microscope. The bundles consist of about 40 unenclosed standard cilia supported by one or two primary sense cells with centrally directed axons of 0.1–0.2 diameter. Axons in the distal portions of the branchial crown occur in small bundles surrounded by a basement membrane. More centrally, glial elements appear and the nerves are surrounded by a collagenous sheath. The branchial nerve trunk shows similarities in organisation to other previously investigated annelid central nervous tissue in that the whole nerve is surrounded by a fibrous sheath central to which there is a layer of glial cells with processes penetrating a central neuropile. The 0.1–0.2 axons commonly occur in glial-enveloped groups of < 40 whilst other axons of larger and mixed diameter are found together.Each tentacle has two branchial nerves on the oral side, and each nerve gives rise to two small 75-axon branches running to each pinnule. The branchial nerves fuse to form the branchial nerve trunk running to the supra-oesophageal ganglia.Sections of the branchial nerves of the branchial crown at progressively more central levels show that the branchial nerve trunk contains enough axons of 0.1–0.2 diameter to account for all the sensory cells on the tentacles. This is taken as evidence for the sensory cells having axons terminating within the central nervous system and that there is no peripheral confluence or fusion of these afferent axons.     

The Analysis of Sensory Data by Generalized Linear Model

The use of generalized linear model theory in formulating and testing hypotheses which may arise in the analysis of ordinal scale organoleptic data is illustrated.     

Sensory gating and its modulation by cannabinoids: electrophysiological, computational and mathematical analysis

Gating of sensory information can be assessed using an auditory conditioning-test paradigm which measures the reduction in the auditory evoked response to a test stimulus following an initial conditioning stimulus. Recording brainwaves from specific areas of the brain using multiple electrodes is helpful in the study of the neurobiology of sensory gating. In this paper, we use such technology to investigate the role of cannabinoids in sensory gating in the CA3 region of the rat hippocampus. Our experimental results show that application of the exogenous cannabinoid agonist WIN55,212-2 can abolish sensory gating. We have developed a phenomenological model of cannabinoid dynamics incorporated within a spiking neural network model of CA3 with synaptically interacting pyramidal and basket cells. Direct numerical simulations of this model suggest that the basic mechanism for this effect can be traced to the suppression of inhibition of slow GABA_B synapses. Furthermore, by working with a simpler mathematical firing rate model we are able to show the robustness of this mechanism for the abolition of sensory gating.     

Analysis of the Acid Phosphatases of Rat Sensory Gangli by Isoelectric Focussing on Polyacrylamide Gels

The acid phosphatases of rat spinal and trigeminal ganglia have been separated by isoelectric focussing on polyacrylamide gels into two main classes with pI's of 7.1 and 5.4. A low-pI acid phosphatase is also present in the mouse but not in the guinea pig. Evidence is presented that in the rat the pI 5.4 enzyme represents the nonlysosomal acid phosphatase that has been identified histochemically in one population of sensory neurones. This pI 5.4 acid phosphatase is partly membrane-bound and is selectively depleted by capsaicin administration. In lumbar dorsal root ganglia the enzyme is selectively depleted by sectioning the sciatic nerve and undergoes rapid axonal transport, a greater amount being transported peripherally than centrally. The results are discussed with reference to the possible function of this nonlysosomal acid phosphatase.     

Sensory acquisition in active sensing systems

A defining feature of active sensing is the use of self-generated energy to probe the environment. Familiar biological examples include echolocation in bats and dolphins and active electrolocation in weakly electric fish. Organisms that utilize active sensing systems can potentially exert control over the characteristics of the probe energy, such as its intensity, direction, timing, and spectral characteristics. This is in contrast to passive sensing systems, which rely on extrinsic energy sources that are not directly controllable by the organism. The ability to control the probe energy adds a new dimension to the task of acquiring relevant information about the environment. Physical and ecological constraints confronted by active sensing systems include issues of signal propagation, attenuation, speed, energetics, and conspicuousness. These constraints influence the type of energy that organisms use to probe the environment, the amount of energy devoted to the process, and the way in which the nervous system integrates sensory and motor functions for optimizing sensory acquisition performance.     

Molecular Analysis of Endoplasmic Reticulum Stress Response After Global Forebrain Ischemia/Reperfusion in Rats: Effect of Neuroprotectant Simvastatin

Simvastatin is a cholesterol-lowering agent whose functional significance and neuroprotective mechanism in ischemic brain injury is not yet solved. The purpose of this study is to evaluate the effect of simvastatin on ischemic brain injury. We examined the endoplasmic reticulum stress response (UPR/unfolded protein response), by measuring the mRNA and protein levels of specific genes such as ATF6, GRP78, and XBP1 after 15 min 4-VO ischemia and different times of reperfusion (1, 3, and 24 h). The results from the group of naïve ischemic rats were compared with results from the group of pre-treated animals with simvastatin. The results of the experiments showed significant increase in all genes at the mRNA level in ischemic phase (about 43% for XBP1, 58% for GRP78, and 39% for ATF6 more than control). The protein level of XBP1 was decreased in pre-treated animals at ischemic phase and first hour of reperfusion (about 15% less), and did not reach control levels. The protein levels of GRP78 were maximal at third hour of reperfusion in statin group with a small decrease at 24 h of reperfusion in both groups. The levels of ATF6 mRNA in statin-treated animals was higher in comparison to non-statin animals at the ischemic phase and the third hour of reperfusion (about 35% higher), which was also translated into the higher protein level. This could indicate that one of the main proteins targeted to enhance neuroprotective effect to ER during the first two hours of reperfusion was ATF6 protein, the levels of which were 60% higher than in non-treated animals. These data suggest that simvastatin, in addition to the proposed neuroprotective effect, exerts a neuroprotective role in the attenuation of ER stress response after acute ischemic/reperfusion insult.     

Modeling and Analysis of the Molecular Basis of Pain in Sensory Neurons

Intracellular calcium dynamics are critical to cellular functions like pain transmission. Extracellular ATP plays an important role in modulating intracellular calcium levels by interacting with the P2 family of surface receptors. In this study, we developed a mechanistic mathematical model of ATP-induced P2 mediated calcium signaling in archetype sensory neurons. The model architecture, which described 90 species connected by 162 interactions, was formulated by aggregating disparate molecular modules from literature. Unlike previous models, only mass action kinetics were used to describe the rate of molecular interactions. Thus, the majority of the 252 unknown model parameters were either association, dissociation or catalytic rate constants. Model parameters were estimated from nine independent data sets taken from multiple laboratories. The training data consisted of both dynamic and steady-state measurements. However, because of the complexity of the calcium network, we were unable to estimate unique model parameters. Instead, we estimated a family or ensemble of probable parameter sets using a multi-objective thermal ensemble method. Each member of the ensemble met an error criterion and was located along or near the optimal trade-off surface between the individual training data sets. The model quantitatively reproduced experimental measurements from dorsal root ganglion neurons as a function of extracellular ATP forcing. Hypothesized architecture linking phosphoinositide regulation with P2X receptor activity explained the inhibition of P2X-mediated current flow by activated metabotropic P2Y receptors. Sensitivity analysis using individual and the whole system outputs suggested which molecular subsystems were most important following P2 activation. Taken together, modeling and analysis of ATP-induced P2 mediated calcium signaling generated qualitative insight into the critical interactions controlling ATP induced calcium dynamics. Understanding these critical interactions may prove useful for the design of the next generation of molecular pain management strategies.     

Synthesis and Sensory Studies of Umami‐Active Scaffolds

The class of 2‐isopropyl‐5‐methylbicyclo[4.1.0]heptane‐7‐carboxamides, 1 – 4 , has been identified as potent umami‐tasting molecules. A scalable synthesis of this challenging scaffold and new sensory insights will be presented. Interestingly, the umami characteristics differ remarkably, depending on constitutional and stereochemical features of the parent scaffold. During our studies, we could identify the carboxamide moiety as a crucial factor to influence the umami intensity of these scaffolds. In addition, the configuration of the cyclopropyl moiety exerts some influence, whereas the absolute configuration of the menthyl scaffold, at least the tested D ‐ and L ‐configuration, is less important.     

Microbial Metabolism as an Evolutionary Response: The Cybernetic Approach to Modeling

ABSTRACT:?

The growth and metabolic capabilities of microorganisms depend on their interactions with the culture medium. Many media contain two or more key substrates, and an organism may have different preferences for the components. Microorganisms adjust their preferences according to the prevailing conditions so as to favor their own survival. Cybernetic modeling describes this evolutionary strategy by defining a goal that an organism tries to attain optimally at all times. The goal is often, but not always, maximization of growth, and it may require the cells to manipulate their metabolic processes in response to changing environmental conditions.

The cybernetic approach overcomes some of the limitations of metabolic control analysis (MCA), but it does not substitute MCA. Here we review the development of the cybernetic modeling of microbial metabolism, how it may be combined with MCA, and what improvements are needed to make it a viable technique for industrial fermentation processes.

IMTECH communication no.001/2001     

Sensory basis for sound intensity discrimination in the bushcricket Requena verticalis (Tettigoniidae, Orthoptera)

The ability of the female bushcricket, Requena verticalis, to discriminate between two conspecific sound signals that differed in sound pressure level (SPL) was tested in a two-choice paradigm. Significant discrimination was achieved with a 2-dB difference. The property of each pair of receptors to establish binaural discharge differences was investigated in electrophysiological experiments. The threshold to the conspecific signal varies for each fibre from about 40 to 90 dB SPL, allowing for a range fractionation of the hearing organ. Each pair of receptors establishes significant binaural discharge differences only within a restricted intensity range about 10 dB above threshold. Based on a model of the intensity response function of a receptor the total discharge of the 22 receptors in both ears was calculated with monaural and binaural stimulation. The profile of receptors exhibiting significant discharge differences changes with increasing SPL, from the most sensitive fibres with a characteristic frequency between 12 kHz and 35 kHz at low SPLs to the least sensitive fibres at very low and high characteristic frequencies at medium to high SPLs. The discharge difference with an intensity difference of 2 dB is rather small (4% of the total receptor activity) and limited only to a few pairs of receptors. Accepted: 8 November 1997     

Lithium Chloride Inhibits the Phosphorylation of Newly Synthesized Neurofilament Protein, NF-M, in Cultured Chick Sensory Neurons

The middle and high molecular weight members of the neurofilament triplet, NF-M and NF-H, undergo extensive posttranslational polyphosphorylation, a process requiring 24 h or more for completion. We have investigated ways of perturbing this process in intact cells and have found that phosphorylation of newly synthesized NF-M in cultured chick sensory neurons is inhibited by Li+. [35S]Methionine pulse-chase experiments were carried out with pure neuronal cultures, and the phosphorylation of newly synthesized NF-M was monitored by following the accompanying change, with chase time, in apparent size and charge of the polypeptide. Addition of LiCl to the medium inhibited this mobility shift in a dose-dependent manner over concentrations between 2 and 25 mM. Incorporation of 32P into NF-M, as well as NF-H, was also inhibited, whereas incorporation into the low molecular weight neurofilament protein, beta-tubulin, and total protein was unaffected. Protein synthesis was not altered. Exposure to 25 mM LiCl for up to 72 h was not toxic, and the inhibition of NF-M phosphorylation was completely reversible. When 25 mM Li+ was added after NF-M had become partially phosphorylated, further progression was blocked, but there was no net dephosphorylation or degradation of NF-M. Additional experiments suggest that this action of Li+ is probably not due to effects on second messenger levels or to effects on tubulin metabolism and assembly state presented in our accompanying article, but rather to interference by Li+ itself, with the phosphorylation of NF-M and NF-H by specific neurofilament kinase(s).     

Psychophysiological Profile in Dyssynergic Defecation Patients: An Individual and Situational Response Specificity Analysis

The aim of this study was to evaluate the temporal stability and the situational specificity of the intra-anal EMG-activity, as well as the individual specificity of this response in dyssynergic defecation patients. With this purpose, 26 individuals (13 with dyssynergic defecation and 13 without anorectal pathology) participated in two sessions of psychophysiological assessment, with an inter-session period of 1 week. At each session, the EMG-activity of external anal sphincter was recorded under four different conditions (baseline, voluntary contraction, reflex contraction and simulated defecation). The findings provide empirical evidence about temporal stability of the intra-anal EMG-activity, situational specificity of this response and the existence of a specific profile of intra-anal EMG-activity characteristic of patients with dyssynergic defecation.     

Sensory neurons and peripheral pathways in Drosophila embryos

Summary The thoracic and abdominal segments of the Drosophila embryo contain 373 neurons innervating external sensory structures and 162 neurons innervating chordotonal organs. These neurons are arranged in ventral, lateral and dorsal clusters within each segment, in a highly invariant pattern. Two fascicles are formed in each segment as the sensory axons grow ventrally towards the CNS and meet motor axons growing dorsally from the CNS. In all but the last segment, the anterior fascicle is contributed by the dorsal and lateral neurons, while the posterior one is formed by the ventral neurons. Five distinct segmental patterns are described, corresponding to (1) the prothorax, (2) the other two thoracic segments, (3) the first seven abdominal segments, (4) the eighth and (5) the ninth (and possibly the tenth) abdominal segments.The publisher regrets that two companion papers unfortunately were published out of sequence. The present paper should have preceded the paper entitled The sense organs in the Drosophila larva and their relation to the embryonic pattern of sensory neurons, which appeared in Volume 195, Number 4 of the journal (pp 222–228)     

蛇类红外线感受系统:一种可能的外气功研究实验动物模型

许多蛇类,例如响尾蛇属,洞蛇属,饭匙倩蛇属,竹叶青蛇属和蝮蛇属等在头部具有一对能在黑暗中探测和捕获猎物的凹陷器官。这种凹陷器官对红外射线非常敏感,因此也称为红外线感受器官。凹陷器官在中间部位被一层约为15μm厚的薄膜(红外线感受膜)分隔为外腔和内腔,红外线感受膜由三叉神经节中的特化假单极神经细胞(红外线感受细胞)的外周轴突所支配,红外线感受膜内相邻的游离神经末梢聚合形成约40μm直径的团块,构成了基本的红外线感受野单元。三叉神经节中的红外线感受细胞的中枢轴突投射到同侧延髓中的三叉神经束外侧降核,该神经核团为此类蛇属所特有。从三叉神经束外侧降核二级神经元发出的轴突投射到对侧视顶盖。由于蛇类不具有分化的半球新皮质,因此视顶盖为红外线感受系统的感觉与行为的整合中枢。在三叉神经节,延髓三叉神经束外侧降核及视顶盖均可记录到神经细胞对红外线刺激的反应电位,从而可观察红外线刺激强度与各级红外线感受神经元反应强度的关系。本文简述了蛇类红外线感受系统的形态学和生理学特征及其研究进展,并且探讨了利用蛇类红外线感受系统作为生物体接受外气功研究的实验动物模型的可能性。     

Sensory and autonomic innervation of non-hairy and hairy human skin

Summary Non-hairy and hairy human skin were investigated with the use of the indirect immunohistochemical technique employing antisera to different neuronal and non-neuronal structural proteins and neurotransmitter candidates. Fibers immunoreactive to antisera against neurofilaments, neuron-specific enolase, myelin basic protein, protein S-100, substance P, neurokinin A, neuropeptide Y, tyrosine hydroxylase and vasoactive intestinal polypeptide (VIP) were detected in the skin with specific distributional patterns. Neurofilament-, neuron-specific enolase-, myelin basic protein-, protein S-100-, substance P-, neurokinin A-and vasoactive intestinal polypeptide (VIP)-like immunoreactivities were found in or in association with sensory nerves; moreover, neuron-specific enolase-, myelin basic protein-, protein S-100, neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities occurred in or in association with autonomic nerves. It was concluded that antiserum against neurofilaments labels sensory nerve fibers exclusively, whereas neuron-specific enolase-, myelin basic protein- and protein S-100-like immunoreactivities are found in or in association with both sensory and autonomic nerves. Substance P- and neurokinin A-like immunoreactivities were observed only in sensory nerve fibers, and neuropeptide Y- and tyrosine hydroxylase-like immunoreactivities occurred only in autonomic nerve fibers, whereas vasoactive intestinal polypeptide (VIP)-like immunoreactivity was seen predominantly in autonomic nerves, but also in some sensory nerve fibers.     

Activation of Protein Kinase C by the Capsaicin Analogue Resiniferatoxin in Sensory Neurones

Abstract: Resiniferatoxin and capsaicin are sensory neurone-specific excitotoxins that operate a common cation channel in nociceptors. Resiniferatoxin is structurally similar to capsaicin and to phorbol esters. Specific [³H]-resiniferatoxin binding, which was detected in the membrane ( K _D value 1.8 ± 0.2 n M ) but not cytosolic fraction of rat dorsal root ganglia, could not be displaced by phorbol 12,13-dibutyrate. Conversely, resiniferatoxin did not displace [³H]phorbol 12,13-dibutyrate binding in either the cytosolic or membrane fraction. Resiniferatoxin and capsaicin both caused translocation of protein kinase C in dorsal root ganglion neurones (EC₅₀ value 18 ± 3 n M ). This translocation was greatly reduced but not abolished, in the absence of external Ca²⁺, suggesting that it was secondary to Ca²⁺ entry. Resiniferatoxin also caused direct activation of a Ca²⁺- and lipid-dependent kinase (or kinases) in the cytosolic fraction of dorsal root ganglia, at concentrations (100 n M to 10 µ M ) higher than required for displacement of [³H]resiniferatoxin binding or translocation of protein kinase C. Capsaicin (up to 10 µ M ) was unable to mimic this effect. These data imply that although resiniferatoxin-induced translocation of protein kinase C in dorsal root ganglion neurones was mainly indirect, it also caused direct activation of a protein kinase C-like kinase in these cells.     

Chemical Composition and Sensory Evaluation of Fermented Tea with Medicinal Mushrooms

In commercial tea production, plenty of tea leaf waste is generated, which may not only exert pollution risk to environment, but also a huge waste of bioactive ingredients in tea. In this study, the 4th to 7th leaves of tea bush were collected and used as substrate for mycelial culture of two renown medicinal mushrooms Grifola frondosa and Tianzhi (new variants of Ganoderma lucidum) to obtain a new type of solid-state fermented tea. Result showed that the polysaccharides of Grifola frondosa and Tianzhi fermented tea were 1.52 and 4.14 %, tea polyphenols were 1.51 and 1.85 %, the free amino acids were 1.52 and 0.94 %, caffeine were 1.16 and 1.70 %, polyphenols/amid acids ratio were 1.0 and 1.98, water extractions were 35.53 and 32.86 %, protein contents were 17.63 and 6.13 mg/g, respectively. The volatile components were mainly composed of alcohols, esters, aldehydes and ketones. The contents of major flavor compositions of fermented tea had changed and their relation tended to be harmonious, and the variety of amino acids significantly increased. Therefore, the sensory flavor and therapeutic qualities of fermented tea were significantly improved.     

Modeling of the Psychophysical Response Curves Using the Grand Canonical Ensemble in Statistical Physics

This paper aims to investigate the peripheral mechanism of taste perception by the use of the grand canonical ensemble in statistical physics. It allows a better understanding of this process and its interpretation at a microscopic level. The experimental part allowed us to obtain psychophysical curves relative to four nutritive sweeteners (sucrose, fructose, glucose, and maltitol). These curves represent the intensity of sweetness as a function of sugar concentration in water. A Sensory Measuring Unit for Recording Flux (SMURF) device is used to obtain intensity–time curves for each of the studied sweeteners. To model these curves we have established the expressions of some models using grand canonical ensemble formalism in statistical physics and applying some simplification approaches. The fitting of the psychophysical data with statistical models by numerical simulation demonstrates a good correlation between the models and the experimental curves. Some physicochemical parameters interfere in the expression of the established models. These parameters are classified in two categories: on one hand, the steric aspect, which is manifested by the density of taste receptor site, and the number of molecules per receptor site and on the other hand, an energetic aspect illustrated by the concentration at half saturation, which gives indirectly the sweet molecule-receptor site energy of interaction.