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Introduction: The dopamine D5 receptor (D5R) shows high expression in cortical regions, yet the role of the receptor in learning and memory remains poorly understood. This study evaluated the impact of prefrontal cortical (PFC) D5R knockdown in rats on learning and memory and assessed the role of the D5R in the regulation of neuronal oscillatory activity and glycogen synthase kinase-3 (GSK-3β), processes integral to cognitive function., Materials and Methods: Using an adeno-associated viral (AAV) vector, male rats were infused with shRNA to the D5R bilaterally into the PFC. Local field potential recordings were taken from freely moving animals and spectral power and coherence were evaluated in, and between, the PFC, orbitofrontal cortex (OFC), hippocampus (HIP), and thalamus. Animals were then assessed in object recognition, object location, and object in place tasks. The activity of PFC GSK-3β, a downstream effector of the D5R, was evaluated., Results: AAV-mediated knockdown of the D5R in the PFC induced learning and memory deficits. These changes were accompanied by elevations in PFC, OFC, and HIP theta spectral power and PFC-OFC coherence, reduced PFC-thalamus gamma coherence, and increased PFC GSK-3β activity., Conclusion: This work demonstrates a role for PFC D5Rs in the regulation of neuronal oscillatory activity and learning and memory. As elevated GSK-3β activity has been implicated in numerous disorders of cognitive dysfunction, this work also highlights the potential of the D5R as a novel therapeutic target via suppression of GSK-3β., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Vanguard efforts in forecasting volcanic eruptions are turning to physics-based models, which require quantitative estimates of magma conditions during pre-eruptive storage. Below active arc volcanoes, observed magma storage depths vary widely (~0 to 20 kilometers) and are commonly assumed to represent levels of neutral buoyancy. Here we show that geophysically observed magma depths (6 ± 3 kilometers) are greater than depths of neutral buoyancy, ruling out this commonly assumed control. Observed depths are instead consistent with predicted depths of water degassing. Intrinsically wetter magmas degas water and crystallize deeper than dry magmas, resulting in viscosity increases that lead to deeper stalling of ascending magma. The water-depth relationship provides a critical constraint for forecasting models by connecting depth of eruption initiation to its volatile fuel.

Estimates of changes in the frequency or height of contemporary extreme sea levels (ESLs) under various climate change scenarios are often used by climate and sea level scientists to help communicate the physical basis for societal concern regarding sea level rise. Changes in ESLs (i.e., the hazard) are often represented using various metrics and indicators that, when anchored to salient impacts on human systems and the natural environment, provide useful information to policy makers, stakeholders, and the general public. While changes in hazards are often anchored to impacts at local scales, aggregate global summary metrics generally lack the context of local exposure and vulnerability that facilitates translating hazards into impacts. Contextualizing changes in hazards is also needed when communicating the timing of when projected ESL frequencies cross critical thresholds, such as the year in which ESLs higher than the design height benchmark of protective infrastructure (e.g., the 100-year water level) are expected to occur within the lifetime of that infrastructure. We present specific examples demonstrating the need for such contextualization using a simple flood exposure model, local sea level rise projections, and population exposure estimates for 414 global cities. We suggest regional and global climate assessment reports integrate global, regional, and local perspectives on coastal risk to address hazard, vulnerability and exposure simultaneously., Supplementary Information: The online version contains supplementary material available at 10.1007/s10584-021-03288-6., (© The Author(s) 2022.)

Mitragyna speciosa ("kratom"), employed as a traditional medicine to improve mood and relieve pain, has shown increased use in Europe and North America. Here, the dose-dependent effects of a purified alkaloid kratom extract on neuronal oscillatory systems function, analgesia, and antidepressant-like behaviour were evaluated and kratom-induced changes in ΔFosB expression determined. Male rats were administered a low or high dose of kratom (containing 0.5 or 1 mg/kg of mitragynine, respectively) for seven days. Acute or repeated low dose kratom suppressed ventral tegmental area (VTA) theta oscillatory power whereas acute or repeated high dose kratom increased delta power, and reduced theta power, in the nucleus accumbens (NAc), prefrontal cortex (PFC), cingulate cortex (Cg) and VTA. The repeated administration of low dose kratom additionally elevated delta power in PFC, decreased theta power in NAc and PFC, and suppressed beta and low gamma power in Cg. Suppressed high gamma power in NAc and PFC was seen selectively following repeated high dose kratom. Both doses of kratom elevated NAc-PFC, VTA-NAc, and VTA-Cg coherence. Low dose kratom had antidepressant-like properties whereas both doses produced analgesia. No kratom-induced changes in ΔFosB expression were evident. These results support a role for kratom as having both antidepressant and analgesic properties that are accompanied by specific changes in neuronal circuit function. However, the absence of drug-induced changes in ΔFosB expression suggest that the drug may circumvent this cellular signaling pathway, a pathway known for its significant role in addiction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Buckhalter, Soubeyrand, Ferrone, Rasmussen, Manduca, Al-Abdul-Wahid, Frie, Khokhar, Akhtar and Perreault.)

Ketamine is a promising therapeutic for treatment-resistant depression (TRD) but is associated with an array of short-term psychomimetic side-effects. These disparate drug effects may be elicited through the modulation of neural circuit activity. The purpose of this study was to therefore delineate dose- and time-dependent changes in ketamine-induced neural oscillatory patterns in regions of the brain implicated in depression. Wistar-Kyoto rats were used as a model system to study these aspects of TRD neuropathology whereas Wistar rats were used as a control strain. Animals received a low (10 mg/kg) or high (30 mg/kg) dose of ketamine and temporal changes in neural oscillatory activity recorded from the prefrontal cortex (PFC), cingulate cortex (Cg), and nucleus accumbens (NAc) for ninety minutes. Effects of each dose of ketamine on immobility in the forced swim test were also evaluated. High dose ketamine induced a transient increase in theta power in the PFC and Cg, as well as a dose-dependent increase in gamma power in these regions 10-min, but not 90-min, post-administration. In contrast, only low dose ketamine normalized innate deficits in fast gamma coherence between the NAc-Cg and PFC-Cg, an effect that persisted at 90-min post-injection. These low dose ketamine-induced oscillatory alterations were accompanied by a reduction in immobility time in the forced swim test. These results show that ketamine induces time-dependent effects on neural oscillations at specific frequencies. These drug-induced changes may differentially contribute to the psychomimetic and therapeutic effects of the drug., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Deep uncertainty describes situations when there is either ignorance or disagreement over (1) models used to describe key system processes and (2) probability distributions used to characterize the uncertainty of key variables and parameters. Future projections of Antarctic ice sheet (AIS) mass loss remain characterized by deep uncertainty. This complicates decisions on long-lived coastal protection projects when determining what margin of safety to implement. If the chosen margin of safety does not properly account for uncertainties in sea level rise, the effectiveness of flood protection could decrease over time, potentially putting lives and properties at a greater risk. To address this issue, we develop a flood damage allowance framework for calculating the height of a flood protection strategy needed to ensure that a given level of financial risk is maintained. The damage allowance framework considers decision maker preferences such as planning horizons, protection strategies, and subjective views of AIS stability. We use Manhattan-with the population and built environment fixed in time-to illustrate how our framework could be used to calculate a range of damage allowances based on multiple plausible scenarios of AIS melt. Under high greenhouse gas emissions, we find that results are sensitive to the selection of the upper limit of AIS contributions to sea level rise. Design metrics that specify financial risk targets, such as expected flood damage, allow for the calculation of avoided flood damages (i.e., benefits) that can be combined with estimates of construction cost and then integrated into existing financial decision-making approaches (e.g., benefit-cost analysis)., (©2020. The Authors.)

Uncertainties in Representative Concentration Pathway (RCP) scenarios and Antarctic Ice Sheet (AIS) melt propagate into uncertainties in projected mean sea-level (MSL) changes and extreme sea-level (ESL) events. Here we quantify the impact of RCP scenarios and AIS contributions on 21st-century ESL changes at tide-gauge sites across the globe using extreme-value statistics. We find that even under RCP2.6, almost half of the sites could be exposed annually to a present-day 100-year ESL event by 2050. Most tropical sites face large increases in ESL events earlier and for scenarios with smaller MSL changes than extratropical sites. Strong emission reductions lower the probability of large ESL changes but due to AIS uncertainties, cannot fully eliminate the probability that large increases in frequencies of ESL events will occur. Under RCP8.5 and rapid AIS mass loss, many tropical sites, including low-lying islands face a MSL rise by 2100 that exceeds the present-day 100-year event level.

Estimates of climate change damage are central to the design of climate policies. Here, we develop a flexible architecture for computing damages that integrates climate science, econometric analyses, and process models. We use this approach to construct spatially explicit, probabilistic, and empirically derived estimates of economic damage in the United States from climate change. The combined value of market and nonmarket damage across analyzed sectors-agriculture, crime, coastal storms, energy, human mortality, and labor-increases quadratically in global mean temperature, costing roughly 1.2% of gross domestic product per +1°C on average. Importantly, risk is distributed unequally across locations, generating a large transfer of value northward and westward that increases economic inequality. By the late 21st century, the poorest third of counties are projected to experience damages between 2 and 20% of county income (90% chance) under business-as-usual emissions (Representative Concentration Pathway 8.5)., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Climate change is expected to increase global mean temperatures leading to higher tropospheric ozone (O3) concentrations in already polluted regions, potentially eroding the benefits of expensive emission controls. The magnitude of the "O3-climate penalty" has generally decreased over the past three decades, which makes future predictions for climate impacts on air quality uncertain. Researchers attribute historical reductions in the O3-climate penalty to reductions in NOx emissions but have so far not extended this theory into a quantitative prediction for future effects. Here, we show that a three-dimensional air quality model can be used to map the behavior of the O3-climate penalty under varying NOx and VOC emissions in both NOx-limited and NOx-saturated conditions in Central and Southern California, respectively. Simulations suggest that the planned emissions control program for O3 precursors will not diminish the O3-climate penalty to zero as some observational studies might imply. The results further demonstrate that in a NOx-limited air basin, NOx control strategies alone are sufficient to both decrease the O3-climate penalty and mitigate O3 pollution, while in a NOx-saturated air basin, a modified emissions control plan that carefully chooses reductions in both NOx and VOC emissions may be necessary to eliminate the O3-climate penalty while simultaneously reducing base case O3 concentrations to desired levels. Additional modeling is needed to determine the behavior of the O3-climate penalty as NOx and VOC emissions evolve in other regions.