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Increased activity of dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens of rats during a 'decision' period reflects a 'loss' outcome of the previous decision and predicts a subsequent safe choice; by artificially increasing the activity of D2R neurons during the decision period, risk-seeking rats could be converted to risk-avoiding rats. The neural correlates of risk perception Some people are risk-seekers and others risk-avoiders, and even risk-avoiders sometimes make risky choices; the neural substrate of this variability is not known. Karl Deisseroth and colleagues show in rats that increased activity of dopamine receptor type 2 (D2R)-expressing cells in the nucleus accumbens during a 'decision' period reflects a 'loss' outcome of the previous decision and predicts a subsequent safe choice. Individual differences in the size of the activity increase correlated with risk preference. By artificially increasing the activity of D2R neurons during the decision period, the authors could turn risk-seeking rats into risk-avoiding rats. These results indicate that state and trait variations in risk preference are controlled by D2R-expressing nucleus accumbens neurons. A marked bias towards risk aversion has been observed in nearly every species tested.sup.1,2,3,4. A minority of individuals, however, instead seem to prefer risk (repeatedly choosing uncertain large rewards over certain but smaller rewards), and even risk-averse individuals sometimes opt for riskier alternatives.sup.2,5. It is not known how neural activity underlies such important shifts in decision-making--either as a stable trait across individuals or at the level of variability within individuals. Here we describe a model of risk-preference in rats, in which stable individual differences, trial-by-trial choices, and responses to pharmacological agents all parallel human behaviour. By combining new genetic targeting strategies with optical recording of neural activity during behaviour in this model, we identify relevant temporally specific signals from a genetically and anatomically defined population of neurons. This activity occurred within dopamine receptor type-2 (D2R)-expressing cells in the nucleus accumbens (NAc), signalled unfavourable outcomes from the recent past at a time appropriate for influencing subsequent decisions, and also predicted subsequent choices made. Having uncovered this naturally occurring neural correlate of risk selection, we then mimicked the temporally specific signal with optogenetic control during decision-making and demonstrated its causal effect in driving risk-preference. Specifically, risk-preferring rats could be instantaneously converted to risk-averse rats with precisely timed phasic stimulation of NAc D2R cells. These findings suggest that individual differences in risk-preference, as well as real-time risky decision-making, can be largely explained by the encoding in D2R-expressing NAc cells of prior unfavourable outcomes during decision-making., Author(s): Kelly A. Zalocusky [sup.1] [sup.2] [sup.3] , Charu Ramakrishnan [sup.1] [sup.3] , Talia N. Lerner [sup.1] [sup.3] , Thomas J. Davidson [sup.1] [sup.3] , Brian Knutson [sup.4] , Karl [...]

How the brain selects appropriate sensory inputs and suppresses distractors is unknown. Given the well-established role of the prefrontal cortex (PFC) in executive function (1), its interactions with sensory cortical areas during attention have been hypothesized to control sensory selection (2-5). To test this idea and, more generally, dissect the circuits underlying sensory selection, we developed a cross-modal divided-attention task in mice that allowed genetic access to this cognitive process. By optogenetically perturbing PFC function in a temporally precise window, the ability of mice to select appropriately between conflicting visual and auditory stimuli was diminished. Equivalent sensory thalamocortical manipulations showed that behaviour was causally dependent on PFC interactions with the sensory thalamus, not sensory cortex. Consistent with this notion, we found neurons of the visual thalamic reticular nucleus (visTRN) to exhibit PFC-dependent changes in firing rate predictive of the modality selected. visTRN activity was causal to performance as confirmed by bidirectional optogenetic manipulations of this subnetwork. Using a combination of electrophysiology and intracellular chloride photometry, we demonstrated that visTRN dynamically controls visual thalamic gain through feedforward inhibition. Our experiments introduce a new subcortical model of sensory selection, in which the PFC biases thalamic reticular subnetworks to control thalamic sensory gain, selecting appropriate inputs for further processing., To dissect the circuit basis of sensory selection, we sought a behaviour capable of dividing attention across modalities in the freely behaving mouse. Building on the rich history of visual [...]

Macrophyte invasive alien species (IAS) fitness is often hypothesised to be associated with beneficial environmental conditions (environmental matching) or species‐poor communities. However, positive correlations between macrophyte IAS abundance and native plant richness can also arise, due to habitat heterogeneity (defined here as variation in abiotic and native biotic conditions over space and time). We analysed survey and palaeoecological data for macrophytes in satellite lakes along the Upper Lough Erne (ULE) system (Northern Ireland, UK), covering a gradient of eutrophication and connectivity to partition how environmental conditions, macrophyte diversity and habitat heterogeneity explained the abundance of Elodea canadensis, a widely distributed non‐native macrophyte in Europe. E. canadensis abundance positively correlated with macrophyte richness at both the within‐ and between‐lake scales indicating coexistence of native and invasive species over time. E. canadensis was also more prolific in highly connected and macrophyte‐rich lakes, but sparser in the more eutrophic‐isolated ones. Partial boosted regression trees revealed that in eutrophic‐isolated lakes, E. canadensis abundances correlated with water clarity (negatively), plant diversity (positively), and plant cover (negatively) whereas in diverse‐connected lakes, beta diversity (both positively and negatively) related to most greatly E. canadensis abundance. Dense macrophyte cover and unfavourable environmental conditions thus appear to confer invasibility resistance and sufficient habitat heterogeneity to mask any single effect of native biodiversity or environmental matching in controlling E. canadensis abundance. Therefore, in shallow lake landscapes, habitat heterogeneity variously enables the coexistence of native macrophytes and E. canadensis, reducing the often‐described homogenisation effects of invasive macrophytes. [ABSTRACT FROM AUTHOR]

Socio-economic and racial/ethnic disparities in healthcare quality have been the point of huge discussion and debate. There is currently a public debate over healthcare legislation in the United States to eliminate the disparities in healthcare. We reviewed the literature and critically examined standard socio-economic and racial/ethnic measurement approaches. As a result of the literature review, we identified and discussed the limitations in existing quality assessment for identifying and addressing these disparities. The aim of this research was to investigate the difference between health outcomes based on patients' ability to pay and ethnic status during a single emergency admission. We conducted a multifactorial analysis using the 11-year admissions data from a single hospital to test the bias in short-term health outcomes for length of stay and death rate, based on 'payment type' and 'race', for emergency hospital admissions. Inconclusive findings for racial bias in outcomes may be influenced by different insurance and demographic profiles by race. As a result, we found that the Self-Pay (no insurance) category has the shortest statistically significant length of stay. While the differences between Medicare, Private and Government are not significant, Self-Pay was significantly shorter. That 'Whites' have more Medicare (older) patients than 'Blacks' might possibly lead to a longer length of stay and higher death rate for the group. [ABSTRACT FROM AUTHOR]

Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal and external stimuli is unclear. Here we show in mice that excitatory neural populations in the lamina terminalis form a hierarchical circuit architecture to regulate thirst. Among them, nitric oxide synthase-expressing neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Conversely, a distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of GLP1R-expressing MnPO neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. Our study reveals dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behaviour to maintain internal water balance., Author(s): Vineet Augustine [1, 2]; Sertan Kutal Gokce [2]; Sangjun Lee [2]; Bo Wang [2]; Thomas J. Davidson [3]; Frank Reimann [4]; Fiona Gribble [4]; Karl Deisseroth [5, 6]; Carlos [...]

One way to compare health care needs and outcomes on common scales is by estimating the strength of preferences or willingness-to-pay (WTP). The aim of this study was to review directly measured preference values and WTP estimates for health states treated by plastic surgery. The included articles had to meet the criteria defined in the SPIDER (Sample, Phenomenon of Interest, Design, Evaluation, Research type). Relevant databases were searched using predetermined strings. Data were extracted in a standardised manner. Included studies were appraised according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach for rating the importance of outcomes. In total, 213 abstracts were retrieved. Of these, 179 did not meet the inclusion criteria and were excluded, leaving 34 studies in the review. The risk of bias was considered moderate in four studies and serious in the rest. The overall certainty of evidence for directly measured preference values and WTP estimates for health states treated by plastic surgery is low (Grade ƟƟОО). The lowest preference scores were generally elicited for facial defects/anomalies and the highest for excess skin after massive weight loss. Scientific knowledge about preferences and the resulting health gains might play an essential role in deciding which procedures should be considered for public funding or rather rationed within the system. Better quality studies are required to allow for such applications. [ABSTRACT FROM AUTHOR]

Alpine peatlands are recognized as a major natural contributor to the budgets of atmospheric methane (CH4) but as a weak nitrous oxide (N2O) source. Anthropogenic activities and climate change have put these fragile nitrogen (N)-limited peatlands under pressure by altering water table (WT) levels and enhancing N deposition. The response of greenhouse gas (GHG) emissions from these peatlands to these twin changes is uncertain. To address this knowledge gap, we conducted a mesocosm experiment in 2018 and 2019 investigating individual and interactive effects of three WT levels (WT-30, 30 cm below soil surface; WT0, soil-water interface; WT10, 10 cm above soil surface) and multiple levels of N deposition (0, 20, 40, 80 and 160 kg N ha-1 yr-1) on growing season CH4 and N2O emissions in the Zoige alpine peatland, Qinghai-Tibetan Plateau. We found that the elevated WT levels increased CH4 emission, while the N deposition had non-linear effects (stimulation at moderate levels and inhibition at higher). In contrast no clear pattern of the effect of WT levels on the cumulative N2O emission was evident, while N deposition led to a consistent and linear increase (emission factor: 2.3%-2.8% and 1% in IPCC), and this was dependent on the WT levels. Across the two years, the scenario with the greatest GWP (from CH4 and N2O) was an N deposition of ca. 20 kg N ha-1 yr-1 and high WT levels (at soil surface or above). Given the current N deposition in the Zoige alpine peatland (1.08-17.81 kg N·ha-1), our results suggested that the CH4 and N2O emissions from the alpine peatlands could greatly increase in response to the possible doubling N deposition in the future. We believe that our results provide insights into how interactions between climate change and human disturbance will alter GHG emissions from this globally important habitat. [ABSTRACT FROM AUTHOR]

Obtaining high-resolution information from a complex system, while maintaining the global perspective needed to understand system function, represents a key challenge in biology. Here we address this challenge with a method (termed CLARITY) for the transformation of intact tissue into a nanoporous hydrogel-hybridized form (crosslinked to a three-dimensional network of hydrophilic polymers) that is fully assembled but optically transparent and macromolecule-permeable. Using mouse brains, we show intact-tissue imaging of long-range projections, local circuit wiring, cellular relationships, subcellular structures, protein complexes, nucleic acids and neurotransmitters. CLARITY also enables intact-tissue in situ hybridization, immunohistochemistry with multiple rounds of staining and de-staining in non-sectioned tissue, and antibody labelling throughout the intact adult mouse brain. Finally, we show that CLARITY enables fine structural analysis of clinical samples, including non-sectioned human tissue from a neuropsychiatric-disease setting, establishing a path for the transmutation of human tissue into a stable, intact and accessible form suitable for probing structural and molecular underpinnings of physiological function and disease., The extraction of detailed structural and molecular information from intact biological systems has long been a fundamental challenge across fields of investigation, and has spurred considerable technological innovation (1,8). The [...]