Clustering Analysis for Sorting ATP-Induced Nociceptive Firing in rat Meninges

© 2016, Springer Science+Business Media New York.We previously reported the pronociceptive effect of extracellular ATP on meningeal branches of the trigeminal nerve. Based on this, we proposed ATP-driven purinergic mechanisms as important contributors to migraine pain. However, the neurochemical profile of the single nociceptive fibers composing the trigeminal nerve remained unsolved. Here, we present a clustering approach to separate and characterize ATP-induced nociceptive spikes obtained from the trigeminal nerve using a suction electrode. By combining a number of procedures to ensure adequate separation of spikes into clearly distinguishable clusters, we were able to reconstruct single fiber activity, which was characterized by a uniformity of spike shapes and specific signatures of the autocorrelation function. This allows us to reveal, at single fiber level, the sustained time-course of responses to ATP and their respective firing frequencies. These firing frequencies predicted the temporal summation of pain signals in the brainstem and spinal cord. Our findings contribute to a better understanding of the peripheral purinergic mechanisms of trigeminal pain, including migraine pain, and suggest a novel reliable approach for testing other pronociceptive agents potently implicated in migraine

The infrastructure of public catering in the context of tourist city space development

To assess the impact of environmental factors on the activities of catering enterprises of the Belgorod region and the quality of customer service, the authors proposed a method using STEP-analysis and SWOT-analysis. The analysis of environmental factors was carried out on the basis of the expert evaluation results conducted in two stage

Transformation of museum product

Today, each museum needs to develop an active strategy of market development, which is preceded by a comprehensive analysis of potential consumers of the museum product, on the basis of which the directions of development will be proposed. The conducted research allowed us to reveal a number of problems which are connected with necessity of transformation of the museum product providing satisfaction of visitor’s requirements and, at the same time, increase in the income of the museu

Acid Sensitive Ion Channels as Target of Hydrogen Sulfide in Rat Trigeminal Neurons

© 2016, Springer Science+Business Media New York.Hydrogen sulfide (H2S), an endogenous gasotransmitter, was proposed to act as a signaling molecule in a wide variety of pathophysiological processes including inflammation and nociception. Acid-sensing ion channels (ASICs) are voltage-insensitive, proton-gated cation channels activated by extracellular acidosis, and are involved in various pathologies of the nervous system including ischemia, stroke, and migraine. In this study, the effect of the H2S donor-sodium hydrogen sulfide (NaHS) on the firing of trigeminal (TG) nerve was explored using suction electrode recordings in peripheral branches of the TG nerve in isolated rat meninges, and patch clamp recordings of ASIC currents in isolated TG neurons. NaHS (100 μM) increased the action potential frequency of TG nerve and bath application of NaHS increased the amplitude of ASIC currents triggered by focal application of low pH solution on isolated TG neurons. We propose that activation of ASICs by H2S during chronic inflammation process contributes to the increased excitability of the TG system and may be implicated in the generation of nociceptive firing underlying migraine pain

Resting membrane potential of the rat ventroposteriomedial thalamic neurons during postnatal development

Resting membrane potential is a critical parameter determining tonic or bursting mode of the thalamic neurons function. Previous developmental studies using whole-cell recordings revealed strongly depolarized values ofthe resting membrane potential (near -50 mV) in the immature VPM and LGN thalamic neurons. Yet, whole-cell recordings are associated with an introduction of the shunting conductance via the gigaseal that may lead to neuronal depolarization in small neurons with high, in the gigaohm range, membrane resistance. Therefore, we have performed measurements of the resting potential of VPM neurons in slices obtained from neonatal rats of postnatal days P2-P7 using cell-attached recordings of NMDA channels as voltage sensors. Because the currents through NM DA channels reverse near 0 mV, we assumed that the resting membrane potential should equal the reversal potential of currents through NMDA channels in cell-attached recordings. Analysis of the current-voltage relationships of NMDA currents revealed that the resting membrane potential in the immature VPM neurons is around -74 mV and that it does not change during the first postnatal week. This suggests that VPM neurons may operate in the bursting mode during the early postnatal period and support the oscillatory activity (spindle-like bursts) in the developing thalamocortical networks

Improvement of Nociceptive Spike Clusterization with Shape Approximation

© 2017, Springer Science+Business Media, LLC. Cluster spike analysis is widely used for studies of neuronal activity when electrical signals are sorted out and grouped according to the different shapes. We recently applied this method to sort out the nociceptive spikes in the trigeminal nerve implicated in generation of migraine pain. However, the electrical noise leading to less accuracy of calculated spike parameters often hinder the correct sorting of nerve signals. In this study, in order to improve the accuracy of calculations, we explored the prior approximation of spike shapes before applying clusterization. The prior fitting of spike shapes allowed us to extract signal parameters much more precisely and detect the strongly increased number of spike clusters which is close to the expected number of fibers in the trigeminal nerve. Prior approximation improved cluster analysis outcomes and, importantly, revealed new clusters that demonstrated the different functional properties, suggesting that their function was previously hidden within the multiple firing

Hunting for origins of migraine pain: cluster analysis of spontaneous and capsaicin-induced firing in meningeal trigeminal nerve fibers

International audienceTrigeminal nerves in meninges are implicated in generation of nociceptive firing underlying migraine pain. However, the neurochemical mechanisms of nociceptive firing in meningeal trigeminal nerves are little understood. In this study, using suction electrode recordings from peripheral branches of the trigeminal nerve in isolated rat meninges, we analyzed spontaneous and capsaicin-induced orthodromic spiking activity. In control, biphasic single spikes with variable amplitude and shapes were observed. Application of the transient receptor potential vanilloid 1 (TRPV1) agonist capsaicin to meninges dramatically increased firing whereas the amplitudes and shapes of spikes remained essentially unchanged. This effect was antagonized by the specific TRPV1 antagonist capsazepine. Using the clustering approach, several groups of uniform spikes (clusters) were identified. The clustering approach combined with capsaicin application allowed us to detect and to distinguish "responder" (65%) from "non responder" clusters (35%). Notably, responders fired spikes at frequencies exceeding 10 Hz, high enough to provide postsynaptic temporal summation of excitation at brainstem and spinal cord level. Almost all spikes were suppressed by tetrodotoxin (TTX) suggesting an involvement of the I I X-sensitive sodium channels in nociceptive signaling at the peripheral branches of trigeminal neurons. Our analysis also identified transient (desensitizing) and long-lasting (slowly desensitizing) responses to the continuous application of capsaicin. Thus, the persistent activation of nociceptors in capsaicin-sensitive nerve fibers shown here may be involved in trigeminal pain signaling and plasticity along with the release of migraine-related neuropeptides from TRPV1 positive neurons. Furthermore, cluster analysis could be widely used to characterize the temporal and neurochemical profiles of other pain transducers likely implicated in migraine

Influence of CSP 310 and CSP 310-like proteins from cereals on mitochondrial energetic activity and lipid peroxidation in vitro and in vivo

BACKGROUND: The development of chilling and freezing injury symptoms in plants is known to frequently coincide with peroxidation of free fatty acids. Mitochondria are one of the major sources of reactive oxygen species during cold stress. Recently it has been suggested that uncoupling of oxidation and phosphorylation in mitochondria during oxidative stress can decrease ROS formation by mitochondrial respiratory chain generation. At the same time, it is known that plant uncoupling mitochondrial protein (PUMP) and other UCP-like proteins are not the only uncoupling system in plant mitochondria. All plants have cyanide-resistant oxidase (AOX) whose activation causes an uncoupling of respiration and oxidative phosphorylation. Recently it has been found that in cereals, cold stress protein CSP 310 exists, and that this causes uncoupling of oxidation and phosphorylation in mitochondria. RESULTS: We studied the effects of CSP 310-like native cytoplasmic proteins from a number of cereal species (winter rye, winter wheat, Elymus and maize) on the energetic activity of winter wheat mitochondria. This showed that only CSP 310 (cold shock protein with molecular weight 310 kD) caused a significant increase of non-phosphorylative respiration. CSP 310-like proteins of other cereals studied did not have any significant influence on mitochondrial energetic activity. It was found that among CSP 310-like proteins only CSP 310 had prooxidant activity. At the same time, Elymus CSP 310-like proteins have antioxidant activity. The study of an influence of infiltration by different plant uncoupling system activators (pyruvate, which activates AOX, and linoleic acid which is a substrate and activator for PUMP and CSP 310) showed that all of these decreased lipid peroxidation during cold stress. CONCLUSIONS: Different influence of CSP 310-like proteins on mitochondrial energetic activity and lipid peroxidation presumably depend on the various subunit combinations in their composition. All the plant cell systems that caused an uncoupling of oxidation and phosphorylation in plant mitochondria can participate in plant defence from oxidative damage during cold stress

Receptor mechanisms mediating the pro-nociceptive action of hydrogen sulfide in rat trigeminal neurons and meningeal afferents

© 2017 Koroleva, Mustafina, Yakovlev, Hermann, Giniatullin and Sitdikova. Hydrogen sulfide (H 2 S), a well-established member of the gasotransmitter family, is involved in a variety of physiological functions, including pro-nociceptive action in the sensory system. Although several reports have shown that H 2 S activates sensory neurons, the molecular targets of H 2 S action in trigeminal (TG) nociception, implicated in migraine, remains controversial. In this study, using suction electrode recordings, we investigate the effect of the H 2 S donor, sodium hydrosulfide (NaHS), on nociceptive firing in rat meningeal TG nerve fibers. The effect of NaHS was also explored with p atch-clamp and calcium imaging techniques on isolated TG neurons. NaHS dramatically increased the nociceptive firing in TG nerve fibers. This effect was abolished by the TRPV1 inhibitor capsazepine but was partially prevented by the TRPA1 blocker HC 030031. In a fraction of isolated TG neurons, NaHS transiently increased amplitude of capsaicin-induced currents. Moreover, NaHS by itself induced inward currents in sensory neurons, which were abolished by the TRPV1 inhibitor capsazepine suggesting involvement of TRPV1 receptors. In contrast, the inhibitor of TRPA1 receptors HC 030031 did not prevent the NaHS-induced currents. Imaging of a large population of TG neurons revealed that NaHS induced calcium transients in 41% of tested neurons. Interestingly, this effect of NaHS in some neurons was inhibited by the TRPV1 antagonist capsazepine whereas in others it was sensitive to the TRPA1 blocker HC 030031. Our data suggest that both TRPV1 and TRPA1 receptors play a role in the pro-nociceptive action of NaHS in peripheral TG nerve endings in meninges and in somas of TG neurons. We propose that activation of TRPV1 and TRPA1 receptors by H 2 S during neuro-inflammation conditions contributes to the nociceptive firing in primary afferents underlying migraine pain

Automated Information System for Personnel Training in the Field of Professional Education

Рассматривается концепция автоматизированной информационной системы, которую можно использовать в сфере профессионального образования для подготовки кадров. Приведена классификация необходимой ERP-системы. Выведены основные особенности подготовки кадров в цифровом производстве.The concept of an automated information system that can be used in the field of education for staff training is considered. The classification of the ERP system is given. The main features of staff training in digital production are formulated