D1R/GluN1 complexes in the striatum integrate dopamine and glutamate signalling to control synaptic plasticity and cocaine-induced responses.

Convergent dopamine and glutamate signalling onto the extracellular signal-regulated kinase (ERK) pathway in medium spiny neurons (MSNs) of the striatum controls psychostimulant-initiated adaptive processes underlying long-lasting behavioural changes. We hypothesised that the physical proximity of dopamine D1 (D1R) and glutamate NMDA (NMDAR) receptors, achieved through the formation of D1R/NMDAR complexes, may act as a molecular bridge that controls the synergistic action of dopamine and glutamate on striatal plasticity and behavioural responses to drugs of abuse. We found that concomitant stimulation of D1R and NMDAR drove complex formation between endogenous D1R and the GluN1 subunit of NMDAR. Conversely, preventing D1R/GluN1 association with a cell-permeable peptide (TAT-GluN1C1) left individual D1R and NMDAR-dependent signalling intact, but prevented D1R-mediated facilitation of NMDAR-calcium influx and subsequent ERK activation. Electrophysiological recordings in striatal slices from mice revealed that D1R/GluN1 complexes control the D1R-dependent enhancement of NMDAR currents and long-term potentiation in D1R-MSN. Finally, intra-striatal delivery of TAT-GluN1C1 did not affect acute responses to cocaine but reduced behavioural sensitization. Our findings uncover D1R/GluN1 complexes as a major substrate for the dopamine-glutamate interaction in MSN that is usurped by addictive drugs to elicit persistent behavioural alterations. They also identify D1R/GluN1 complexes as molecular targets with a therapeutic potential for the vast spectrum of psychiatric diseases associated with an imbalance between dopamine and glutamate transmission

The potential use of climate forecasts by community water system managers

This study investigates the possible use of climate forecasts by Pennsylvania Community Water System (CWS) managers for planning and decision making. The first phase involves analysis of data from a mail survey to identify managers most likely to use climate forecasts. The second phase uses semi-structured interviews with the managers of large surface-water systems to determine the extent to which they currently use forecasts, the circumstances in which they would be most likely to integrate forecasts into their planning, and the formats that would encourage them to use forecasts. Analysis of the survey data demonstrates that managers of the largest systems are more likely to use forecasts than managers of smaller systems. The interviews reveal that theses VWS managers do not currently use climate forecasts for planning, even under extreme drought, but that there are circumstances in which they would consider doing so. In a broader context, the findings suggest that when scientists work with decision-makers, they should be prepared, first to learn about the decision-making context, then to put the information of concern into that context and, finally, to work closely with the decision-makers to help them gain experience using that information

The potential use of climate forecasts by community water system managers

This study investigates the possible use of climate forecasts by Pennsylvania Community Water System (CWS) managers for planning and decision making. The first phase involves analysis of data from a mail survey to identify managers most likely to use climate forecasts. The second phase uses semi-structured interviews with the managers of large surface-water systems to determine the extent to which they currently use forecasts, the circumstances in which they would be most likely to integrate forecasts into their planning, and the formats that would encourage them to use forecasts. Analysis of the survey data demonstrates that managers of the largest systems are more likely to use forecasts than managers of smaller systems. The interviews reveal that theses VWS managers do not currently use climate forecasts for planning, even under extreme drought, but that there are circumstances in which they would consider doing so. In a broader context, the findings suggest that when scientists work with decision-makers, they should be prepared, first to learn about the decision-making context, then to put the information of concern into that context and, finally, to work closely with the decision-makers to help them gain experience using that information.Resource /Energy Economics and Policy,

The Mouse Models of Human Cancer database (MMHCdb)

The laboratory mouse has served for decades as an informative animal model system for investigating the genetic and genomic basis of cancer in humans. Although thousands of mouse models have been generated, compiling and aggregating relevant data and knowledge about these models is hampered by a general lack of compliance, in the published literature, with nomenclature and annotation standards for genes, alleles, mouse strains and cancer types. The Mouse Models of Human Cancer database (MMHCdb) is an expertly curated, comprehensive knowledgebase of diverse types of mouse models of human cancer, including inbred mouse strains, genetically engineered mouse models, patient-derived xenografts, and mouse genetic diversity panels such as the Collaborative Cross. The MMHCdb is a FAIR-compliant knowledgebase that enforces nomenclature and annotation standards, and supports the completeness and accuracy of searches for mouse models of human cancer and associated data. The resource facilitates the analysis of the impact of genetic background on the incidence and presentation of different tumor types, and aids in the assessment of different mouse strains as models of human cancer biology and treatment response

Emotional labour and transnational domestic work: The moving geographies of 'Maid abuse' in Singapore

10.1080/17450100701381557Mobilities22195-21

Impaired Hippocampus-Dependent and Facilitated Striatum-Dependent Behaviors in Mice Lacking the Delta Opioid Receptor

International audiencePharmacological data suggest that delta opioid receptors modulate learning and memory processes. In the present study, we investigated whether inactivation of the delta opioid receptor modifies hippocampus (HPC)- and striatum-dependent behaviors. We first assessed HPC-dependent learning in mice lacking the receptor (Oprd1(-/-) mice) or wild-type (WT) mice treated with the delta opioid antagonist naltrindole using novel object recognition, and a dual-solution cross-maze task. Second, we subjected mutant animals to memory tests addressing striatum-dependent learning using a single-solution response cross-maze task and a motor skill-learning task. Genetic and pharmacological inactivation of delta opioid receptors reduced performance in HPC-dependent object place recognition. Place learning was also altered in Oprd1(-/-) animals, whereas striatum-dependent response and procedural learning were facilitated. Third, we investigated the expression levels for a large set of genes involved in neurotransmission in both HPC and striatum of Oprd1(-/-) mice. Gene expression was modified for several key genes that may contribute to alter hippocampal and striatal functions, and bias striatal output towards striatonigral activity. To test this hypothesis, we finally examined locomotor effects of dopamine receptor agonists. We found that Oprd1(-/-) and naltrindole-treated WT mice were more sensitive to the stimulant locomotor effect of SKF-81297 (D1/D5), supporting the hypothesis of facilitated striatonigral output. These data suggest, for the first time, that delta receptor activity tonically inhibits striatal function, and demonstrate that delta opioid receptors modulate learning and memory performance by regulating the HPC/striatum balance