| 1. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Abel, I, et al.
(författare)
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Overview of the JET results with the ITER-like wall
- 2013
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
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Tidskriftsartikel (refereegranskat)abstract
- Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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| 4. |
- Romanelli, F, et al.
(författare)
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Overview of the JET results
- 2011
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
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Tidskriftsartikel (refereegranskat)abstract
- Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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| 5. |
- Aad, G., et al.
(författare)
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- 2012
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swepub:Mat__t (refereegranskat)
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| 6. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 7. |
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| 8. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
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| 10. |
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| 11. |
- Abe, O, et al.
(författare)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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| 12. |
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| 13. |
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| 14. |
- Adcox, K, et al.
(författare)
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PHENIX detector overview
- 2003
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Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - 0167-5087. ; 499:2-3, s. 469-479
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Tidskriftsartikel (refereegranskat)abstract
- The PHENIX detector is designed to perform a broad study of A-A, p-A, and p-p collisions to investigate nuclear matter under extreme conditions. A wide variety of probes, sensitive to all timescales, are used to study systematic variations with species and energy as well as to measure the spin structure of the nucleon. Designing for the needs of the heavy-ion and polarized-proton programs has produced a detector with unparalleled capabilities. PHENIX measures electron and muon pairs, photons, and hadrons with excellent energy and momentum resolution. The detector consists of a large number of subsystems that are discussed in other papers in this volume. The overall design parameters of the detector are presented. (C) 2002 Elsevier Science B.V. All rights reserved.
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| 15. |
- Behrens, RH, et al.
(författare)
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Transparency in publishing
- 2004
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Ingår i: Journal of travel medicine. - 1195-1982. ; 11:4, s. 263-263
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Biro, Z, et al.
(författare)
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5-HT Modulation of identified segmental premotor interneurons in the lamprey spinal cord
- 2006
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 96:2, s. 931-935
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Tidskriftsartikel (refereegranskat)abstract
- Ipsilaterally projecting spinal excitatory interneurons (EINs) generate the hemisegmental rhythmic locomotor activity in lamprey, while the commissural interneurons ensure proper left-right alternation. 5-HT is a potent modulator of the locomotor rhythm and is endogenously released from the spinal cord during fictive locomotion. The effect of 5-HT was investigated for three segmental premotor interneuron types: EINs, commissural excitatory and commissural inhibitory interneurons. All three types of interneurons produced chemical postsynaptic potentials in motoneurons, but only those from EINs had an electrical component. The effect of 5-HT was studied on the slow afterhyperpolarization, involved in spike frequency regulation, and on the segmental synaptic transmission to motoneurons. 5-HT induced a reduction in the slow afterhyperpolarization and a depression of synaptic transmission in all three types of segmental interneurons. Thus 5-HT is a very potent modulator of membrane properties and synaptic transmission of last-order segmental premotor interneurons. Such modulation of locomotor network interneurons can partially account for the observed effects of 5-HT on the swimming pattern in lamprey.
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| 17. |
- Biro, Z, et al.
(författare)
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The activity of spinal commissural interneurons during fictive locomotion in the lamprey
- 2008
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 100:2, s. 716-722
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Tidskriftsartikel (refereegranskat)abstract
- Commissural interneurons in the lamprey coordinate activity of the hemisegmental oscillators to ensure proper left–right alternation during swimming. The activity of interneuronal axons at the ventral commissure was studied together with potential target motoneurons during fictive locomotion in the isolated lamprey spinal cord. To estimate the unperturbed activity of the interneurons, axonal recordings were chosen because soma recordings inevitably will affect the level of membrane depolarization and thereby spike initiation. Of 227 commissural axons recorded during locomotor activity, 14 produced inhibitory and 3 produced excitatory postsynaptic potentials (PSPs) in target motoneurons. The axons typically fired multiple spikes per locomotor cycle, with ∼10 Hz sustained frequency. The average shortest spike interval in a burst corresponded to an instantaneous frequency of ∼50 Hz for both the excitatory and inhibitory axons. The maximum number of spikes per locomotor cycle was inversely related to the locomotor frequency, in accordance with previous observations in the spinal hemicord preparation. In axons that fired multiple spikes per cycle, the mean interspike intervals were in the range in which the amplitude of the slow afterhyperpolarization (sAHP) is large, providing further support for the role of the sAHP in spike timing. One hundred ninety-five axons (86%) fired rhythmically during fictive locomotion, with preferred phase of firing distributed over either the segmental locomotor burst phase (40% of axons) or the transitional phase (between bursts; 60%). Thus in lamprey commissural interneurons, we found a broad distribution of firing rates and phases during fictive locomotion.
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
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| 23. |
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| 24. |
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| 25. |
- Dominguez-Valentin, M, et al.
(författare)
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No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
- 2021
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:13
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Tidskriftsartikel (refereegranskat)abstract
- Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
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| 26. |
- Dominguez-Valentin, M, et al.
(författare)
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Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome. Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT. Results: Risk-reducing hysterectomy and BSO are offered to path_MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (~90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35–55 years). Conclusions: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1, path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Hu, GY, et al.
(författare)
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Intracellular QX-314 causes depression of membrane potential oscillations in lamprey spinal neurons during fictive locomotion
- 2002
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 87:6, s. 2676-2683
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Tidskriftsartikel (refereegranskat)abstract
- Spinal neurons undergo large cyclic membrane potential oscillations during fictive locomotion in lamprey. It was investigated whether these oscillations were due only to synaptically driven excitatory and inhibitory potentials or if voltage-dependent inward conductances also contribute to the depolarizing phase by using N-(2,6-dimethylphenyl carbamoylmethyl)triethylammonium bromide (QX-314) administered intracellularly during fictive locomotion. QX-314 intracellularly blocks inactivating and persistent Na+ channels, and in some neurons, effects on certain other types of channels have been reported. To detail the effects of QX-314 on Na+ and Ca2+ channels, we used dissociated lamprey neurons recorded under whole cell voltage clamp. At low intracellular concentrations of QX-314 (0.2 mM), inactivating Na+ channels were blocked and no effects were exerted on Ca2+ channels (also at 0.5 mM). At 10 mM QX-314, there was, however a marked reduction of I Ca. In the isolated spinal cord of the lamprey, fictive locomotion was induced by superfusing the spinal cord with Ringer's solution containing N-methyl-d-aspartate (NMDA), while recording the locomotor activity from the ventral roots. Simultaneously, identified spinal neurons were recorded intracellularly, while infusing QX-314 from the microelectrode. Patch electrodes cannot be used in the intact spinal cord, and therefore “sharp” electrodes were used. The amplitude of the oscillations was consistently reduced by 20–25% in motoneurons ( P < 0.05) and unidentified spinal neurons ( P < 0.005). The onset of the effect started a few minutes after impalement and reached a stable level within 30 min. These effects thus show that QX-314 causes a reduction in the amplitude of membrane potential oscillations during fictive locomotion. We also investigated whether QX-314 could affect glutamate currents by applying short pulses of glutamate from an extracellular pipette. No changes were observed. We also found no evidence for a persistent Na+ current in dissociated neurons, but these cells have a much-reduced dendritic tree. The results indicate that there is an inward conductance, which is sensitive to QX-314, during membrane potential oscillations that “boosts” the synaptic drive during fictive locomotion. Taken together, the results suggest that inactivating Na+ channels contribute to this inward conductance although persistent Na+channels, if present on dendrites, could possibly also contribute to shaping the membrane potential oscillations.
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| 32. |
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| 35. |
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| 36. |
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| 37. |
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| 38. |
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| 39. |
- Lundkvist, GB, et al.
(författare)
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The suprachiasmatic nucleus exhibits diurnal variations in spontaneous excitatory postsynaptic activity
- 2002
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Ingår i: Journal of biological rhythms. - : SAGE Publications. - 0748-7304 .- 1552-4531. ; 17:1, s. 40-51
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Tidskriftsartikel (refereegranskat)abstract
- A most prominent feature of neurons in the suprachiasmatic nucleus (SCN) is the circadian rhythm in spontaneous firing frequency. To disclose synaptic mechanisms associated with the rhythmic activity, the spontaneous postsynaptic activity was studied using whole-cell, patch clamp recordings in the ventral region of the SCN in slice preparations from rats. The synaptic events were compared between two time intervals corresponding to the highest and lowest electrical activity within the SCN during subjective daytime and nighttime, respectively. The [.gamma]-aminobutyric acid (GABA)–mediated spontaneous inhibitory activity showed no diurnal variations, but the excitatory activity was markedly higher in frequency, without differences in amplitude, during the subjective day compared to the subjective night. Spontaneous and evoked inhibitory synaptic events were blocked by the GABAA receptor antagonist bicuculline. The [.alpha]-amino-hydroxy-5-methylisoxazole-4-propionic acid (AMPA/kainate) receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) blocked most of the excitatory activity. In addition, CNQX reduced the spontaneous inhibitory activity. The N-methyl-D-aspartate antagonist D-2-amino-5-phosphonopentanoic acid reduced the inhibitory activity to a lesser degree, and there was no significant difference in amplitude or frequency of synaptic events in control and Mg2+-free solutions, indicating that the AMPA receptor plays an important role in regulating the inhibitory release of GABAwithin the SCN. Ipsiand contralateral stimulation of the SCN consistently evoked excitatory synaptic responses. Inhibitory synaptic responses occurred in some neurons upon increasing stimulus strength. In conclusion, this study shows that there is a substantial influence from spontaneous glutamatergic synapses on the ventral part of the SCN and that these exhibit daily variations in activity. Diurnal fluctuations in spontaneous excitatory postsynaptic activity within this network may contribute to the mechanisms for synchronization of rhythms between individual SCN neurons and may underlie the daily variations in the spontaneous firing frequency of SCN neurons.
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| 40. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 41. |
- Moller, P, et al.
(författare)
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Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:7, s. 1306-1316
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival.Objective and designThis observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age.Results3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer.ConclusionCarriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient’s age, gender and path_MMR variant. We have updated our open-access website www.lscarisk.org to facilitate this.
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| 42. |
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| 48. |
- Perez, CT, et al.
(författare)
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Endocannabinoids mediate tachykinin-induced effects in the lamprey locomotor network
- 2009
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 102:3, s. 1358-1365
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Tidskriftsartikel (refereegranskat)abstract
- The spinal network underlying locomotion in lamprey is composed of excitatory and inhibitory interneurons mediating fast ionotropic action. In addition, several modulator systems are activated as locomotion is initiated, including the tachykinin system and the metabotropic glutamate receptor 1 (mGluR1), the latter operating partially via the endocannabinoid system. The effects of mGluR1 agonists and tachykinins resemble each other. Like mGluR1 agonists, the tachykinin substance P accelerates the burst rate and reduces the crossed inhibition in an activity-dependent fashion. The present study therefore explores whether tachykinins also use the endocannabinoid system to modulate the locomotor frequency. By monitoring fictive locomotion, we were able to compare the facilitatory effects exerted by applying substance P (1 μM, 20 min), on the burst frequency before and during application of the endocannabinoid CB1 receptor antagonist AM251 (2–5 μM). By using two different lamprey species, we showed that the response to substance P on the burst frequency is significantly reduced during the application of AM251. To examine whether endocannabinoids are involved in the substance P–mediated modulation of reciprocal inhibition, the commissural axons were stimulated, while recording intracellularly from motoneurons. We compare the effect of substance P on the amplitude of the contralateral compound glycinergic inhibitory postsynaptic potential (IPSP) in control and in the presence of AM251. The blockade of CB1 receptors reduced the substance P–mediated decrease in the amplitude by 29%. The present findings suggest that the effects of substance P on the increase in the locomotor burst frequency and depression of IPSPs are mediated partially via release of endocannabinoids acting through CB1 receptors.
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| 49. |
- Perez, CT, et al.
(författare)
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Endogenous tachykinin release contributes to the locomotor activity in lamprey
- 2007
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 97:5, s. 3331-3339
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Tidskriftsartikel (refereegranskat)abstract
- Tachykinins are present in lamprey spinal cord. The goal of this study was to investigate whether an endogenous release of tachykinins contributes to the activity of the spinal network generating locomotor activity. The locomotor network of the isolated lamprey spinal cord was activated by bath-applied N-methyl-d-aspartate (NMDA) and the efferent activity recorded from the ventral roots. When spantide II, a tachykinin receptor antagonist, was bath-applied after reaching a steady-state burst frequency (>2 h), it significantly lowered the burst rate compared with control pieces from the same animal. In addition, the time to reach the steady-state burst frequency (>2 h) was lengthened in spantide II. These data indicate that an endogenous tachykinin release contributes to the ongoing activity of the locomotor network by modulating the glutamate–glycine neuronal network responsible for the locomotor pattern. We also explored the effects of a 10-min exogenous application of substance P (1 μM), a tachykinin, and showed that its effect on the burst rate depended on the initial NMDA induced burst frequency. At low initial burst rates (∼0.5 Hz), tachykinins caused a marked further slowing to 0.1 Hz, whereas at higher initial burst rates, it instead caused an enhanced burst rate as previously reported, and in addition, a slower modulation (0.1 Hz) of the amplitude of the motor activity. These effects occurred during an initial period of ∼1 h, whereas a modest long-lasting increase of the burst rate remained after >2 h.
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| 50. |
- Perez, CT, et al.
(författare)
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Modulation of calcium currents and membrane properties by substance P in the lamprey spinal cord
- 2013
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Ingår i: Journal of neurophysiology. - : American Physiological Society. - 1522-1598 .- 0022-3077. ; 110:2, s. 286-296
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Tidskriftsartikel (refereegranskat)abstract
- Substance P is endogenously released within the locomotor network of the adult lamprey, accelerates the burst frequency of fictive locomotion, and reduces the reciprocal inhibition. Previous studies have shown that dopamine, serotonin, and GABA regulate calcium channels, which control neurotransmitter release, action potential duration, and slow afterhyperpolarization (sAHP). Here we examine the effect of substance P on calcium channels in motoneurons and commissural interneurons using whole cell patch clamp in the lamprey spinal cord. This study analyzed the effects of substance P on calcium currents activated in voltage clamp. We examined the calcium-dependent sAHP in current clamp, to determine the involvement of three calcium channel subtypes modulated by substance P. The effects of substance P on membrane potential and during N-methyl-d-aspartic acid (NMDA) induced oscillations were also analyzed. Depolarizing voltage steps induced inward calcium currents. Substance P reduced the currents carried by calcium by 61% in commissural interneurons and by 31% in motoneurons. Using specific calcium channel antagonists, we show that substance P reduces the sAHP primarily by inhibiting N-type (CaV2.2) channels. Substance P depolarized both motoneurons and commissural interneurons, and we present evidence that this occurs due to an increased input resistance. We also explored the effects of substance P on NMDA-induced oscillations in tetrodotoxin and found it caused a frequency increase. Thus the reduction of calcium entry by substance P and the accompanying decrease of the sAHP amplitude, combined with substance P potentiation of currents activated by NMDA, may both contribute to the increase in fictive locomotion frequency.
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