Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking.

The ventral pallidum is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to the ventral tegmental area (VTA) regulates neuronal activity there. However, the ventral pallidum is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. We found that projections to VTA from the rostral ventral pallidum (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated during cue-induced reinstatement of cocaine seeking--a rat model of relapse in addiction. Moreover, designer receptor-mediated transient inactivation of RVP neurons, their terminals in VTA or functional connectivity between RVP and VTA dopamine neurons blocked the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked cocaine-primed, but not cue-induced, reinstatement. This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations. © 2019, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

Synthesis, structure and mechanism of formation of chalcogen-stabilised mixed-metal clusters featuring acetylide bridging and acetylide coupling

Mild thermolysis of a toluene solution of [(eta(5)-C5H5)Mo(CO)(3)(C=CPh)] and [Fe-3(CO)(9)(mu(3)-E)(2)] (E = S, Se) resulted in the formation of mixed-metal clusters, [(eta(5)-C5H5)(2)Mo2Fe3(CO)(8)(mu(3)-E)(2){eta(5)-CC(Ph)CC(Ph)}] (E = S, 1; Se, 2), [(eta(5)-C5H5)(2)Mo2Fe4(CO)(9)(mu(3)-E)(2)(mu(4)-CCPh)(2)] (E = S, 3; Se, 4) and [(eta(5)-C5H5)(2)Mo2Fe3(CO)(7)(mu(3)-E)(2){mu(5)-CC(Ph)C(Ph)C}] (E = S 5; E = Se 6) which feature head-to-tail coupling of two acetylide groups, two acetylide groups which remain uncoupled and a tail-to-tail coupling of two acetylide groups, respectively, on the chalcogen-bridged Fe/Mo cluster framework. Under similar conditions, the reaction of [(eta(5)-C5H5)W(CO)(3)(C=CPh)] and [Fe-3(CO)(9)(mu(3)-E)(2)] formed the clusters [(eta(5)-C5H5)(2)W2Fe3(CO)(7)(mu(3)-E)(2)(mu(3)-eta(2)-CCPh)(mu(3)-eta(1)-CCH2Ph)] (E = S, 7 or Se, 8) and [(eta(5)-C5H5)WFe2(CO)(8)(mu-CCPh)] (9). All compounds have been characterised by IR and H-1 and C-13 NMR spectroscopy. The Se-bridged compounds have been further characterised by Se-77 NMR spectroscopy. The crystal structures of 1, 3 and 5-9 were elucidated by X-ray diffraction methods