Gz mediates the long-lasting desensitization of brain CB1 receptors and is essential for cross-tolerance with morphine

Abstract Background Although the systemic administration of cannabinoids produces antinociception, their chronic use leads to analgesic tolerance as well as cross-tolerance to morphine. These effects are mediated by cannabinoids binding to peripheral, spinal and supraspinal CB1 and CB2 receptors, making it difficult to determine the relevance of each receptor type to these phenomena. However, in the brain, the CB1 receptors (CB1Rs) are expressed at high levels in neurons, whereas the expression of CB2Rs is marginal. Thus, CB1Rs mediate the effects of smoked cannabis and are also implicated in emotional behaviors. We have analyzed the production of supraspinal analgesia and the development of tolerance at CB1Rs by the direct injection of a series of cannabinoids into the brain. The influence of the activation of CB1Rs on supraspinal analgesia evoked by morphine was also evaluated. Results Intracerebroventricular (icv) administration of cannabinoid receptor agonists, WIN55,212-2, ACEA or methanandamide, generated a dose-dependent analgesia. Notably, a single administration of these compounds brought about profound analgesic tolerance that lasted for more than 14 days. This decrease in the effect of cannabinoid receptor agonists was not mediated by depletion of CB1Rs or the loss of regulated G proteins, but, nevertheless, it was accompanied by reduced morphine analgesia. On the other hand, acute morphine administration produced tolerance that lasted only 3 days and did not affect the CB1R. We found that both neural mu-opioid receptors (MORs) and CB1Rs interact with the HINT1-RGSZ module, thereby regulating pertussis toxin-insensitive Gz proteins. In mice with reduced levels of these Gz proteins, the CB1R agonists produced no such desensitization or morphine cross-tolerance. On the other hand, experimental enhancement of Gz signaling enabled an acute icv administration of morphine to produce a long-lasting tolerance at MORs that persisted for more than 2 weeks, and it also impaired the analgesic effects of cannabinoids. Conclusion In the brain, cannabinoids can produce analgesic tolerance that is not associated with the loss of surface CB1Rs or their uncoupling from regulated transduction. Neural specific Gz proteins are essential mediators of the analgesic effects of supraspinal CB1R agonists and morphine. These Gz proteins are also responsible for the long-term analgesic tolerance produced by single doses of these agonists, as well as for the cross-tolerance between CB1Rs and MORs.</p

The role of stellar radial motions in shaping galaxy surface brightness profiles

Aims. The physics driving features such as breaks observed in galaxy surface brightness (SB) profiles remains contentious. Here, we assess the importance of stellar radial motions in shaping their characteristics. Methods. We use the simulated Milky Way-mass cosmological discs from the Ramses Disc Environment Study (RaDES) to characterise the radial redistribution of stars in galaxies displaying type-I (pure exponentials), II (downbending), and III (upbending) SB profiles. We compare radial profiles of the mass fractions and the velocity dispersions of different sub-populations of stars according to their birth and current location. Results. Radial redistribution of stars is important in all galaxies regardless of their light profiles. Type-II breaks seem to be a consequence of the combined effects of outward-moving and accreted stars. The former produce shallower inner profiles (lack of stars in the inner disc) and accumulate material around the break radius and beyond, strengthening the break; the latter can weaken or even convert the break into a pure exponential. Further accretion from satellites can concentrate material in the outermost parts, leading to type-III breaks that can coexist with type-II breaks, but situated further out. Type-III galaxies would be the result of an important radial redistribution of material throughout the entire disc, as well as a concentration of accreted material in the outskirts. In addition, type-III galaxies display the most efficient radial redistribution and the largest number of accreted stars, followed by type-I and II systems, suggesting that type-I galaxies may be an intermediate case between types-II and III. In general, the velocity dispersion profiles of all galaxies tend to flatten or even increase around the locations where the breaks are found. The age and metallicity profiles are also affected, exhibiting different inner gradients depending on their SB profile, being steeper in the case of type-II systems (as found observationally). The steep type-II profiles might be inherent to their formation rather than acquired via radial redistribution

The X-shooter Spectral Library (XSL): Data Release 3

We present the third data release (DR3) of the X-shooter Spectral Library (XSL). This moderate-to-high resolution, near-ultraviolet-to-near-infrared (350-2480 nm, R similar to 10 000) spectral library is composed of 830 stellar spectra of 683 stars. DR3 improves upon the previous data release by providing the combined de-reddened spectra of the three X-shooter segments over the full 350-2480 nm wavelength range. It also includes additional 20 M-dwarf spectra from the ESO archive. We provide detailed comparisons between this library and Gaia EDR3, MILES, NGSL, CaT library, and (E-)IRTF. The normalised rms deviation is better than D = 0.05 or 5% for the majority of spectra in common between MILES (144 spectra of 180), NGSL (112/116), and (E-)IRTF (55/77) libraries. Comparing synthetic colours of those spectra reveals only negligible offsets and small rms scatter, such as the median offset(rms) 0.001 +/- 0.040 mag in the (box1 - box2) colour of the UVB arm, -0.004 +/- 0.028 mag in (box3 - box4) of the VIS arm, and -0.001 +/- 0.045 mag in (box2 - box3) colour between the UVB and VIS arms, when comparing stars in common with MILES. We also find an excellent agreement between the Gaia published (BP - RP) colours and those measured from the XSL DR3 spectra, with a zero median offset and an rms scatter of 0.037 mag for 449 non-variable stars. The unmatched characteristics of this library, which combine a relatively high resolution, a large number of stars, and an extended wavelength coverage, will help us to bridge the gap between the optical and the near-IR studies of intermediate and old stellar populations, and to probe low-mass stellar systems

Measuring the physical imprints of gas flows in galaxies I: Accretion rate histories

Galaxies are expected to accrete pristine gas from their surroundings to sustain their star formation over cosmic timescales. Its lower abundance affects the metallicity of the ISM in which stars are born, leaving chemical imprints in the stellar populations. We measure the amount of pristine gas that galaxies accrete during their lifetime, using information on the ages and abundances of their stellar populations and a chemical evolution model. We also aim to determine the efficiency of star formation over time. We derived star formation histories and metallicity histories for a sample of 8523 galaxies from the MaNGA survey. We use the former to predict the evolution of the metallicity in a closed-box scenario, and estimate for each epoch the gas accretion rate required to match these predictions with the measured stellar metallicity. Using only chemical parameters, we find that the history of gas accretion depends on the mass of galaxies. More massive galaxies accrete more gas and at higher redshifts than less massive galaxies, which accrete their gas over longer periods. We also find that galaxies with a higher star formation rate at z = 0 have a more persistent accretion history for a given mass. The star formation efficiency shows similar correlations: early-type galaxies and higher-mass galaxies had a higher efficiency in the past, and it declined such that they are less efficient in the present. Our analysis of individual galaxies shows that compactness affects the peak star formation efficiency that galaxies reach, and that the slope of the efficiency history of galaxies with current star formation is flat. Our results support the hypothesis that a steady and substantial supply of pristine gas is required for persistent star formation in galaxies. Once they lose access to this gas supply, star formation comes to a halt.Comment: 17 pages, 11 figures. Accepted at A&

Evidence of ongoing radial migration in NGC 6754: Azimuthal variations of the gas properties

Understanding the nature of spiral structure in disk galaxies is one of the main, and still unsolved questions in galactic astronomy. However, theoretical works are proposing new testable predictions whose detection is becoming feasible with recent development in instrumentation. In particular, streaming motions along spiral arms are expected to induce azimuthal variations in the chemical composition of a galaxy at a given galactic radius. In this letter we analyse the gas content in NGC 6754 with VLT/MUSE data to characterise its 2D chemical composition and H$\alpha$ line-of-sight velocity distribution. We find that the trailing (leading) edge of the NGC 6754 spiral arms show signatures of tangentially-slower, radially-outward (tangentially-faster, radially-inward) streaming motions of metal-rich (poor) gas over a large range of radii. These results show direct evidence of gas radial migration for the first time. We compare our results with the gas behaviour in a $N$-body disk simulation showing spiral morphological features rotating with a similar speed as the gas at every radius, in good agreement with the observed trend. This indicates that the spiral arm features in NGC 6754 may be transient and rotate similarly as the gas does at a large range of radii.Comment: 8 pages, 4 figures, accepted for publication in ApJL 2016 September 2

Evidence for intermediate-age stellar populations in early-type galaxies from K-band spectroscopy

The study of stellar populations in early-type galaxies in different environments is a powerful tool for constraining their star formation histories. This study has been traditionally restricted to the optical range, where dwarfs around the turn-off and stars at the base of the RGB dominate the integrated light at all ages. The near-infrared spectral range is especially interesting since in the presence of an intermediate-age population, AGB stars are the main contributors. In this letter, we measure the near-infrared indices NaI and D$_{\rm CO}$ for a sample of 12 early-type galaxies in low density environments and compare them with the Fornax galaxy sample presented by Silva et al. (2008). The analysis of these indices in combination with Lick/IDS indices in the optical range reveals i) the NaI index is a metallicity indicator as good as C4668 in the optical range, and ii) D$_{\rm CO}$ is a tracer of intermediate-age stellar populations. We find that low-mass galaxies in low density environments show higher NaI and D$_{\rm CO}$ than those located in Fornax cluster, which points towards a late stage of star formation for the galaxies in less dense environments, in agreement with results from other studies using independent methods.Comment: 7 pages, 3 figures, accepted for publication in ApJ

On the Environmental Dependence of Cluster Galaxy Assembly Timescale

We present estimates of CN and Mg overabundances with respect to Fe for early-type galaxies in 8 clusters over a range of richness and morphology. Spectra were taken from the Sloan Digital Sky Survey (SDSS) DR1, and from WHT and CAHA observations. Abundances were derived from absorption lines and single burst population models, by comparing galaxy spectra with appropriately broadened synthetic model spectra. We detect correlations between [Mg/CN] and [CN/Fe] and cluster X-ray luminosity. No correlation is observed for [Mg/Fe]. We also see a clear trend with the richness and morphology of the clusters. This is interpreted given varying formation timescales for CN, Mg and Fe, and a varying star formation history in early-type galaxies as a function of their environment: intermediate-mass early-type galaxies in more massive clusters are assembled on shorter timescales than in less massive clusters, with an upper limit of ~1 Gyr.Comment: Accepted for publication in ApJ Letter

Stellar population gradients in brightest cluster galaxies

We present the stellar population and velocity dispersion gradients for a sample of 24 brightest cluster galaxies (BCGs) in the nearby Universe for which we have obtained high quality long-slit spectra at the Gemini telescopes. With the aim of studying the possible connection between the formation of the BCGs and their host clusters, we explore the relations between the stellar population gradients and properties of the host clusters as well as the possible connections between the stellar population gradients and other properties of the galaxies. We find mean stellar population gradients (negative {\Delta}[Z/H]/log r gradient of -0.285{\pm}0.064; small positive {\Delta}log (age)/log r gradient of 0.069{\pm}0.049; and null {\Delta}[E/Fe]/log r gradient of -0.008{\pm}0.032) that are consistent with those of normal massive elliptical galaxies. However, we find a trend between metallicity gradients and velocity dispersion (with a negative slope of -1.616{\pm}0.539) that is not found for the most massive ellipticals. Furthermore, we find trends between the metallicity gradients and K-band luminosities (with a slope of 0.173{\pm}0.081) as well as the distance from the BCG to the X-ray peak of the host cluster (with a slope of -7.546{\pm}2.752). The latter indicates a possible relation between the formation of the cluster and that of the central galaxy.Comment: 23 pages, 18 figures, accepted for publication in MNRAS. arXiv admin note: text overlap with arXiv:1104.2376v

Census of HII regions in NGC 6754 derived with MUSE: Constraints on the metal mixing scale

We present a study of the HII regions in the galaxy NGC 6754 from a two pointing mosaic comprising 197,637 individual spectra, using Integral Field Spectrocopy (IFS) recently acquired with the MUSE instrument during its Science Verification program. The data cover the entire galaxy out to ~2 effective radii (re ), sampling its morphological structures with unprecedented spatial resolution for a wide-field IFU. A complete census of the H ii regions limited by the atmospheric seeing conditions was derived, comprising 396 individual ionized sources. This is one of the largest and most complete catalogue of H ii regions with spectroscopic information in a single galaxy. We use this catalogue to derive the radial abundance gradient in this SBb galaxy, finding a negative gradient with a slope consistent with the characteristic value for disk galaxies recently reported. The large number of H ii regions allow us to estimate the typical mixing scale-length (rmix ~0.4 re ), which sets strong constraints on the proposed mechanisms for metal mixing in disk galaxies, like radial movements associated with bars and spiral arms, when comparing with simulations. We found evidence for an azimuthal variation of the oxygen abundance, that may be related with the radial migration. These results illustrate the unique capabilities of MUSE for the study of the enrichment mechanisms in Local Universe galaxies.Comment: 13 pages, 7 Figurs, accepted for publishing in A&