Frustrative Nonreward: Behavior, Circuits, Neurochemistry, and Disorders.

The surprising omission or reduction of vital resources (food, fluid, social partners) can induce an aversive emotion known as frustrative nonreward (FNR), which can influence subsequent behavior and physiology. FNR is an integral mediator of irritability/aggression, motivation (substance use disorders, depression), anxiety/fear/threat, learning/conditioning, and social behavior. Despite substantial progress in the study of FNR during the twentieth century, research lagged in the later part of the century and into the early twenty-first century until the National Institute of Mental Health's Research Domain Criteria initiative included FNR and loss as components of the negative valence domain. This led to a renaissance of new research and paradigms relevant to basic and clinical science alike. The COVID-19 pandemic's extensive individual and social restrictions were correlated with increased drug and alcohol use, social conflict, irritability, and suicide, all potential consequences of FNR. This article highlights animal models related to these psychiatric disorders and symptoms and presents recent advances in identifying the brain regions and neurotransmitters implicated.

Flexible Behavioral Adjustment to Frustrative Nonreward in Anticipatory Behavior, but Not in Consummatory Behavior, Requires the Dorsal Hippocampus.

The hippocampus (HC) is recognized for its pivotal role in memory-related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HC's function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in a modified T-maze after reducing the quantity of sugar pellet rewards. In Experiment 2, chemogenetic inhibition of the dorsal HC (dHC) disrupted anticipatory behavior following a food-pellet reward reduction. Experiments 3-5 impaired HC function by using peripheral lipopolysaccharide (LPS) administration. This treatment, which induces peripheral inflammation affecting HC function, significantly increased cytokine levels in the dHC (Experiment 3) and impaired anticipatory choice behavior (Experiment 4). None of these dorsal hippocampal manipulations affected consummatory responses in animals experiencing sucrose downshifts. Accordingly, we found no evidence of increased neural activation in either the dorsal or ventral HC, as measured by c-Fos expression, after a sucrose downshift task involving consummatory suppression (Experiment 6). The results highlight the HC's pivotal role in adaptively modulating anticipatory behavior in response to a variety of situations involving frustrative nonreward, while having no effect on adjustments on consummatory behavior. The data supporting this conclusion were obtained under heterogeneous experimental conditions derived from a multi-laboratory collaboration, ensuring the robustness and high reproducibility of our findings. Spatial orientation, memory update, choice of reward signals of different values, and anticipatory versus consummatory adjustments to reward downshift are discussed as potential mechanisms that could account for the specific effects observed from HC manipulations.

Earth observation data uncover green spaces' role in mental health.

The prevalence of mental health disorders, a key disability cause, is linked to demographic and socioeconomic factors. However, limited data exists on mental health and the urban environment. Urbanization exposes populations to environmental stressors, particularly affecting low-middle-income countries with complex urban arrangements. We used remote sensing and census data to investigate potential connections between environmental factors and mental health disorders. Land cover variables were assessed using the European Space Agency (ESA) global WorldCover product at 10 m resolution together with the database of mental health diagnosed cases (n = 5769) from the Brazilian Unified Health System's Department of Informatics (DATASUS) from every health facility of the city of Porto Alegre. The association of mental health data with land cover was established with machine learning algorithms and polynomial regression models. The results suggest that higher trees cover at neighborhood level was associated with better mental health index. A lower mental health index was also found to be associated with an higher Human Development Index. Our results highlight the potential of greenness in the city environment to achieve substantially better mental health outcomes.

Gut membrane proteins as candidate antigens for immunization of mice against the tick Amblyomma sculptum.

Amblyomma sculptum is widely distributed in Brazil and is the main vector of Rickettsia rickettsii, the causative agent of the Brazilian spotted fever (BSF). Tick gut proteins play an essential role in blood feeding, digestion, and protection of gut epithelium. Therefore, many of these were investigated as potential vaccine targets for tick-control strategies. The present study aimed to select transcripts corresponding to putative immunogenic proteins in the A. sculptum gut epithelial membrane, produce recombinant proteins and evaluate them as antigens against A. sculptum infestations. Three gut proteins - AsMucin, AsAPP, and AsLAMP - and a chimeric protein (rAsChimera) based on 22 peptides containing putative B cell epitopes from seven different gut proteins were evaluated as anti-A. sculptum antigens. Mice immunizations revealed that all recombinant targets elicited humoral response with significantly increased IgG levels compared to controls. For rAsChimera, IgG levels remained significantly higher than controls up to 75 days after the end of the immunization. Challenge trials revealed that vaccination with the chimeric protein was the most effective against A. sculptum, inducing 100 % nymph mortality and reaching 80.8 % efficacy against females. The other three proteins did not induce relevant protection, as AsAPP had only 26.6 % efficacy, whereas AsMucin and AsLAMP induced no protection. These data indicate that targeting gut protein immunogenic regions may be an effective strategy for a vaccine formulation againstA. sculptum.

Biosensors for Public Health and Environmental Monitoring: The Case for Sustainable Biosensing.

Climate change is a profound crisis that affects every aspect of life, including public health. Changes in environmental conditions can promote the spread of pathogens and the development of new mutants and strains. Early detection is essential in managing and controlling this spread and improving overall health outcomes. This perspective article introduces basic biosensing concepts and various biosensors, including electrochemical, optical, mass-based, nano biosensors, and single-molecule biosensors, as important sustainability and public health preventive tools. The discussion also includes how the sustainability of a biosensor is crucial to minimizing environmental impacts and ensuring the long-term availability of vital technologies and resources for healthcare, environmental monitoring, and beyond. One promising avenue for pathogen screening could be the electrical detection of biomolecules at the single-molecule level, and some recent developments based on single-molecule bioelectronics using the Scanning Tunneling Microscopy-assisted break junctions (STM-BJ) technique are shown here. Using this technique, biomolecules can be detected with high sensitivity, eliminating the need for amplification and cell culture steps, thereby enhancing speed and efficiency. Furthermore, the STM-BJ technique demonstrates exceptional specificity, accurately detects single-base mismatches, and exhibits a detection limit essentially at the level of individual biomolecules. Finally, a case is made here for sustainable biosensors, how they can help, the paradigm shift needed to achieve them, and some potential applications.

A link between evolution and society fostering the UN sustainable development goals.

Given the multitude of challenges Earth is facing, sustainability science is of key importance to our continued existence. Evolution is the fundamental biological process underlying the origin of all biodiversity. This phylogenetic diversity fosters the resilience of ecosystems to environmental change, and provides numerous resources to society, and options for the future. Genetic diversity within species is also key to the ability of populations to evolve and adapt to environmental change. Yet, the value of evolutionary processes and the consequences of their impairment have not generally been considered in sustainability research. We argue that biological evolution is important for sustainability and that the concepts, theory, data, and methodological approaches used in evolutionary biology can, in crucial ways, contribute to achieving the UN Sustainable Development Goals (SDGs). We discuss how evolutionary principles are relevant to understanding, maintaining, and improving Nature Contributions to People (NCP) and how they contribute to the SDGs. We highlight specific applications of evolution, evolutionary theory, and evolutionary biology's diverse toolbox, grouped into four major routes through which evolution and evolutionary insights can impact sustainability. We argue that information on both within-species evolutionary potential and among-species phylogenetic diversity is necessary to predict population, community, and ecosystem responses to global change and to make informed decisions on sustainable production, health, and well-being. We provide examples of how evolutionary insights and the tools developed by evolutionary biology can not only inspire and enhance progress on the trajectory to sustainability, but also highlight some obstacles that hitherto seem to have impeded an efficient uptake of evolutionary insights in sustainability research and actions to sustain SDGs. We call for enhanced collaboration between sustainability science and evolutionary biology to understand how integrating these disciplines can help achieve the sustainable future envisioned by the UN SDGs.

Runway extinction in terrestrial toads (Rhinella arenarum): Instrumental or Pavlovian?

Instrumental appetitive extinction involves the reduction of a previously reinforced response when its occurrence is no longer rewarded. Two experiments with terrestrial toads (Rhinella arenarum) tested whether the occurrence of a nonreinforced response is necessary for response extinction by varying the time of exposure to nonrewarded goal-box stimuli across groups. In Experiment 1, toads that received the same acquisition training (15 sessions, 1 session/day, 300 s of access to water in the goal box) were randomly assigned to two groups. In Group 600 (n=12), animals spent 600 s in the goal box in 8 daily extinction sessions (water present but inaccessible). In Group 0 (n=11), toads performed the runway response (i.e., walking from the start to the goal box) but were removed as soon as they entered the goal box, thus having minimal exposure to nonrewarded goal-box stimuli. The runway response was weakened in Group 600 across extinction trials, but exhibited little change in Group 0. In Experiment 2, toads were randomly assigned to two groups after the same acquisition training. Group 0 (n=7) was treated the same as Group 0 in the previous experiment. In Group RI (retention interval, n=7), toads remained in their home cage for 13 days. Finally, all animals received 4 extinction sessions with 300 s in the empty goal box. There was little behavioral change in Group 0 during the 13 sessions with minimal exposure to the goal box. In extinction, both groups reduced their runway response at similar rates. Although the procedures were instrumental, extinction of the runway response in toads can be accounted for in terms of a Pavlovian approach response to stimuli paired with reward and nonreward in the goal box.

Acute psychosocial stress modulates neural and behavioral substrates of cognitive control.

Acute psychosocial stress affects learning, memory, and attention, but the evidence for the influence of stress on the neural processes supporting cognitive control remains mixed. We investigated how acute psychosocial stress influences performance and neural processing during the Go/NoGo task-an established cognitive control task. The experimental group underwent the Trier Social Stress Test (TSST) acute stress induction, whereas the control group completed personality questionnaires. Then, participants completed a functional magnetic resonance imaging (fMRI) Go/NoGo task, with self-report, blood pressure and salivary cortisol measurements of induced stress taken intermittently throughout the experimental session. The TSST was successful in eliciting a stress response, as indicated by significant Stress > Control between-group differences in subjective stress ratings and systolic blood pressure. We did not identify significant differences in cortisol levels, however. The stress induction also impacted subsequent Go/NoGo task performance, with participants who underwent the TSST making fewer commission errors on trials requiring the most inhibitory control (NoGo Green) relative to the control group, suggesting increased vigilance. Univariate analysis of fMRI task-evoked brain activity revealed no differences between stress and control groups for any region. However, using multivariate pattern analysis, stress and control groups were reliably differentiated by activation patterns contrasting the most demanding NoGo trials (i.e., NoGo Green trials) versus baseline in the medial intraparietal area (mIPA, affiliated with the dorsal attention network) and subregions of the cerebellum (affiliated with the default mode network). These results align with prior reports linking the mIPA and the cerebellum to visuomotor coordination, a function central to cognitive control processes underlying goal-directed behavior. This suggests that stressor-induced hypervigilance may produce a facilitative effect on response inhibition which is represented neurally by the activation patterns of cognitive control regions.

Assessing the contribution of nonmarket factors to the market value generated by cow-calf operations in rangelands of the western USA: A true cost accounting approach.

Food system transformation requires a better understanding of the negative and positive externalities involved in food production and consumption. Although negative externalities have received substantial attention, positive externalities have been largely overlooked. True Cost Accounting (TCA) is an economic assessment aimed at accounting for externalities in food systems. The beef industry is an important part of the US food system. In the western USA, beef cattle production is a major land use and economic activity that involves direct links among the cattle, range ecosystems, range management, climate, and ranchers' decisions and welfare. We present a case study based on a TCA assessment to quantify and monetize the contribution of human, social, natural, and produced capitals, as well as farm structure, to the market value generated by cow-calf operations, a key component of the USA beef industry. We estimated an Ordinary Least Square regression model based on indicators of these capitals and of farm structure derived from publicly available data sources at the county level. From model coefficients, we estimated the marginal revenue product of these factors. Results show that nonmarket factors linked with human and social capitals support market performance by contributing to the market value of cow-calf production. These factors operate at scales above the ranch, usually remain hidden, and seldomly are considered in policy decision-making which can lead to policies that inadvertently hamper or eliminate these positive externalities.

How do soil processes control the provision of ecosystem services in coastal wetlands?

Coastal wetlands are known for their diverse ecosystems, yet their soil characteristics are often misunderstood and thought to be monotonous. These soils are frequently subjected to saline water saturation, leading to unique soil processes. However, the combination and intensity of these processes can vary considerably across different ecosystems. In this study, we hypothesize that these diverse soil processes not only govern the geochemical conditions in coastal ecosystems but also influence their ability to deliver ecosystem services. To test this hypothesis, we conducted soil analyses in mangroves, seagrass meadows, and hypersaline tidal flats along the Brazilian coast. We used key soil properties as indicators of soil processes and developed a conceptual model linking soil processes and soil-related ecosystem services in these environments. Under more anoxic conditions, the intense soil organic matter accumulation and sulfidization processes in mangroves evidence their significance in terms of climate regulation through organic carbon sequestration and contaminants immobilization. Similarly, pronounced sulfidization in seagrasses underscores their ability to immobilize contaminants. In contrast, hypersaline tidal flats soils exhibit increased intensities of salinization and calcification processes, leading to a high capacity for accumulating inorganic carbon as secondary carbonates (CaCO3), underscoring their role in climate regulation through inorganic carbon sequestration. Our findings show that contrary to previously thought coastal wetlands are far from monotonous, exhibiting significant variations in the types and intensities of soil processes, which in turn influence their capacity to deliver ecosystem services. This understanding is pivotal for guiding effective management strategies to enhance ecosystem services in coastal wetlands.

Frustrative nonreward: Detailed c-Fos expression patterns in the amygdala after consummatory successive negative contrast.

The amygdala has been implicated in frustrative nonreward induced by unexpected reward downshifts, using paradigms like consummatory successive negative contrast (cSNC). However, existing evidence comes from experiments involving the central and basolateral nuclei on a broad level. Moreover, whether the amygdala's involvement in reward downshift requires a cSNC effect (i.e., greater suppression in downshifted animals than in unshifted controls) or just consummatory suppression without a cSNC effect, remains unclear. Three groups were exposed to (1) a large reward disparity leading to a cSNC effect (32-to-2% sucrose), (2) a small reward disparity involving consummatory suppression in the absence of a cSNC effect (8-to-2% sucrose), and (3) an unshifted control (2% sucrose). Brains obtained after the first reward downshift session were processed for c-Fos expression, a protein often used as a marker for neural activation. c-Fos-positive cells were counted in the anterior, medial, and posterior portions (A/P axis) of ten regions of the rat basolateral, central, and medial amygdala. c-Fos expression was higher in 32-to-2% sucrose downshift animals than in the other two groups in four regions: the anterior and the medial lateral basal amygdala, the medial capsular central amygdala, and the anterior anterio-ventral medial amygdala. None of the areas exhibited differential c-Fos expression between the 8-to-2% sucrose downshift and the unshifted conditions. Thus, amygdala activation requires exposure to a substantial reward disparity. This approach has identified, for the first time, specific amygdala areas relevant to understand the cSNC effect, suggesting follow-up experiments aimed at testing the function of these regions in reward downshift.

Mix-method toolbox for monitoring greenhouse gas production and microbiome responses to soil amendments.

In this study, we adopt an interdisciplinary approach, integrating agronomic field experiments with soil chemistry, molecular biology techniques, and statistics to investigate the impact of organic residue amendments, such as vinasse (a by-product of sugarcane ethanol production), on soil microbiome and greenhouse gas (GHG) production. The research investigates the effects of distinct disturbances, including organic residue application alone or combined with inorganic N fertilizer on the environment. The methods assess soil microbiome dynamics (composition and function), GHG emissions, and plant productivity. Detailed steps for field experimental setup, soil sampling, soil chemical analyses, determination of bacterial and fungal community diversity, quantification of genes related to nitrification and denitrification pathways, measurement and analysis of gas fluxes (N2O, CH4, and CO2), and determination of plant productivity are provided. The outcomes of the methods are detailed in our publications (Lourenço et al., 2018a; Lourenço et al., 2018b; Lourenço et al., 2019; Lourenço et al., 2020). Additionally, the statistical methods and scripts used for analyzing large datasets are outlined. The aim is to assist researchers by addressing common challenges in large-scale field experiments, offering practical recommendations to avoid common pitfalls, and proposing potential analyses, thereby encouraging collaboration among diverse research groups.•Interdisciplinary methods and scientific questions allow for exploring broader interconnected environmental problems.•The proposed method can serve as a model and protocol for evaluating the impact of soil amendments on soil microbiome, GHG emissions, and plant productivity, promoting more sustainable management practices.•Time-series data can offer detailed insights into specific ecosystems, particularly concerning soil microbiota (taxonomy and functions).

Behavioral plasticity in aneural organisms.

Few contemporary psychologists would probably object to the notion that cognitive processes contribute to behavioral plasticity (learning) and are intimately linked to brain function. However, growing evidence suggests that behavioral plasticity is present in organisms lacking neurons (i.e., aneural organisms). This possibility would imply that at least some cognitive processes might have preceded the evolution of nervous systems. Evidence of learning in aneural organisms is reviewed within a mechanistic framework emphasizing four levels of analysis: psychological, neurobiological, neurochemical, and cell-molecular. Learning phenomena ranging from habituation to conditioning have been reported in some aneural organisms, and some key examples are reviewed with attention to evidence of underlying mechanisms. Species comparisons are framed in terms of the central evolutionary concepts of homology and homoplasy. This evidence raises the question of what new behavioral capacities were supported by the evolution of neurons that were not possible before. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Instrumental successive negative contrast in rats: Trial distribution, reward magnitude, and prefrontal cortex activation.

Successive negative contrast (SNC) has been used to study reward relativity, reward loss, and frustration for decades. In instrumental SNC (iSNC), the anticipatory performance of animals downshifted from a large reward to a small reward is compared to that of animals always reinforced with the small reward. iSNC involves a transient deterioration of anticipatory behavior in downshifted animals compared to unshifted controls. There is scattered information on the optimal parameters to produce this effect and even less information about its neural basis. Five experiments with rats trained in a runway to collect food pellets explored the effects of trial distribution (massed or spaced), amount of preshift training, reward disparity, and reward magnitude on the development of an iSNC effect. Start, run, and goal latencies were measured. Using spaced trials (one trial per day), evidence of the iSNC effect was observed with 24 preshift trials and a 32-to-4 pellet disparity. With massed trials (4 trials per session separated by 30-s intertrial intervals), evidence of iSNC was found with 12 preshift sessions (a total of 48 trials) and a 16-to-2 pellet disparity. The massed-training procedure was then used to assess neural activity in three prefrontal cortex areas using c-Fos expression in animals perfused after the first downshift session. There was evidence of increased activation in the anterior cingulate cortex and a trend toward increased activation in the infralimbic and prelimbic cortices. These procedures open a venue for studying the neural basis of the instrumental behavior of animals that experience reward loss.

Soil macrofauna communities in Brazilian land-use systems.

Background: Soil animal communities include more than 40 higher-order taxa, representing over 23% of all described species. These animals have a wide range of feeding sources and contribute to several important soil functions and ecosystem services. Although many studies have assessed macroinvertebrate communities in Brazil, few of them have been published in journals and even fewer have made the data openly available for consultation and further use. As part of ongoing efforts to synthesise the global soil macrofauna communities and to increase the amount of openly-accessible data in GBIF and other repositories related to soil biodiversity, the present paper provides links to 29 soil macroinvertebrate datasets covering 42 soil fauna taxa, collected in various land-use systems in Brazil. A total of 83,085 georeferenced occurrences of these taxa are presented, based on quantitative estimates performed using a standardised sampling method commonly adopted worldwide to collect soil macrofauna populations, i.e. the TSBF (Tropical Soil Biology and Fertility Programme) protocol. This consists of digging soil monoliths of 25 x 25 cm area, with handsorting of the macroinvertebrates visible to the naked eye from the surface litter and from within the soil, typically in the upper 0-20 cm layer (but sometimes shallower, i.e. top 0-10 cm or deeper to 0-40 cm, depending on the site). The land-use systems included anthropogenic sites managed with agricultural systems (e.g. pastures, annual and perennial crops, agroforestry), as well as planted forests and native vegetation located mostly in the southern Brazilian State of Paraná (96 sites), with a few additional sites in the neighbouring states of São Paulo (21 sites) and Santa Catarina (five sites). Important metadata on soil properties, particularly soil chemical parameters (mainly pH, C, P, Ca, K, Mg, Al contents, exchangeable acidity, Cation Exchange Capacity, Base Saturation and, infrequently, total N), particle size distribution (mainly % sand, silt and clay) and, infrequently, soil moisture and bulk density, as well as on human management practices (land use and vegetation cover) are provided. These data will be particularly useful for those interested in estimating land-use change impacts on soil biodiversity and its implications for below-ground foodwebs, ecosystem functioning and ecosystem service delivery. New information: Quantitative estimates are provided for 42 soil animal taxa, for two biodiversity hotspots: the Brazilian Atlantic Forest and Cerrado biomes. Data are provided at the individual monolith level, representing sampling events ranging from February 2001 up to September 2016 in 122 sampling sites and over 1800 samples, for a total of 83,085 ocurrences.

Development of GO Move: A Website for Children With Unilateral Cerebral Palsy.

It is unknown if an online tool is wanted by therapists and parents of individuals with unilateral cerebral palsy (UCP) to support implementation of goal-directed home programs, and if wanted, the recommended features for the tool. The objective was to explore the experiences of therapists and parents who have implemented home programs, seek guidance on translating a paper-based home program toolbox into a mobile website, and develop the website. Qualitative descriptive methodology guided data collection using semi-structured interviews and thematic analysis, validated with field notes and member checking. A team science, iterative approach was used to integrate the themes into the development of the mobile website. Five primary themes including recommendations for the functionality, features, content, and naming of the mobile website were identified. Parents and therapists value home programs. Participants provided recommendations regarding content and features, and the GO Move mobile website was developed based on the recommendations.

Development of Go Move: A Website for Children With Unilateral Cerebral PalsyTherapists and parents of children with unilateral cerebral palsy were interviewed to understand their experience of home programs and gain input for creating a mobile website with information on goal setting and implementing home programs. The interviews provided valuable information about the functionality, features, content, and naming of the website. GO Move, a mobile website aimed to provide information on goal setting, activity selection, and tracking of exercises and activities in the home environment for children with unilateral cerebral palsy, was developed based on the information from the interviews.

Cotton-Like Three-Dimensional Sb4O5Cl2 Structures: Synthesis and Ammonium Hydroxide Sensing.

Nanostructured materials have emerged as valuable tools for the advancement of novel electrocatalysts. Among them, three-dimensional metal oxides have gained significant attention due to their excellent conductivity, cost-effectiveness, and unique design. This study focuses on the synthesis of cotton-like three-dimensional antimony oxychloride (Sb4O5Cl2) structures through a straightforward precipitation method. The nanostructures exhibit immense potential for sensing applications. Electrochemical characterization reveals that the Sb4O5Cl2 heterostructure demonstrates a remarkable double-layer capacitance of 662 F/cm2, accompanied by excellent cyclic stability. The sensor's performance was tested for the detection of ammonium hydroxide (HA) in NaCl solution, yielding sensitivities ranging from 0.95 to 0.140 mA mM-1 cm-2 and a detection limit of 4.54 µM within a wide detection range of 0.3-250 mM. The sensor device possesses a distinctive cotton-like structure and is synthesized through a simple and cost-effective route.

Open field activity is linked to, but is not affected by, the rate of recovery from reward downshift in female Wistar rats.

Frustration is an aversive emotion triggered by unexpected reward downshifts. Using the consummatory successive negative contrast (cSNC) task, a 32-to-2% sucrose downshift was shown to initially suppress consummatory behavior. Such suppression was followed by behavioral recovery over subsequent sessions. Individual differences often emerge in the rate of recovery after the initial consummatory suppression. These experiments were designed to determine whether a stable trait of sensation/novelty seeking (SNS) is related to such individual differences in recovery from reward downshift. In Experiment 1, open field (OF) activity in the central area served as a measure of SNS. A week later, animals received training in the cSNC task involving ten 5-min sessions of access to 32% sucrose followed by four sessions of access to 2% sucrose. Higher OF activity predicted greater consummatory suppression after downshift, but a steeper recovery rate across downshifted sessions. Controls not exposed to the OF showed cSNC, but downshifted animals performed at equivalent levels whether they had OF exposure or not. In Experiment 2, after a 32-to-2% sucrose downshift, fast vs. slow recovery animals displayed similar levels of central activity in the OF. In Experiment 3, animals exhibited similar levels of central activity whether after a 32-to-2% or an 8-to-2% sucrose downshift. In both experiments, activity levels were similar whether immediately after session 12 (onset of recovery) or after session 15 (fully recovered). These results suggest that individual variations in recovery from reward downshift are correlated with levels of SNS as a stable trait.

RAB1A haploinsufficiency phenocopies the 2p14-p15 microdeletion and is associated with impaired neuronal differentiation.

Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and a mosaic missense mutation (c.83T>C [p.Leu28Pro]), were identified in three individuals with similar neurodevelopmental presentations. In rescue experiments, production of the full-length, but not the truncated, RAB1a rescued Golgi structure and cell proliferation in Rab1-depleted cells. In contrast, the missense-variant RAB1a disrupted Golgi structure despite intact Rab1 expression, suggesting a dominant-negative function of the mosaic missense mutation. Knock-down of RAB1A in cultured human embryonic stem cell-derived neurons resulted in impaired neuronal arborization. Finally, RAB1A is located within the 2p14-p15 microdeletion syndrome locus. The similar clinical presentations of individuals with RAB1A loss-of-function mutations and the 2p14-p15 microdeletion syndrome implicate loss of RAB1A in the pathogenesis of neurodevelopmental manifestations of this microdeletion syndrome. Our study identifies a RAB1A-related neurocognitive disorder with speech and motor delay, demonstrates an essential role for RAB1a in neuronal differentiation, and implicates RAB1A in the etiology of the neurodevelopmental sequelae associated with the 2p14-p15 microdeletion syndrome.

Characterizing the mechanisms of social connection.

Understanding how individuals form and maintain strong social networks has emerged as a significant public health priority as a result of the increased focus on the epidemic of loneliness and the myriad protective benefits conferred by social connection. In this review, we highlight the psychological and neural mechanisms that enable us to connect with others, which in turn help buffer against the consequences of stress and isolation. Central to this process is the experience of rewards derived from positive social interactions, which encourage the sharing of perspectives and preferences that unite individuals. Sharing affective states with others helps us to align our understanding of the world with another's, thereby continuing to reinforce bonds and strengthen relationships. These psychological processes depend on neural systems supporting reward and social cognitive function. Lastly, we also consider limitations associated with pursuing healthy social connections and outline potential avenues of future research.