545298 research outputs found
Sort by
A dual-pathway architecture for stress to disrupt agency and promote habit
Get PDFChronic stress can change how we learn and, thus, how we make decisions1-5. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted systems neuroscience approach in male and female mice, we reveal a dual-pathway, amygdala-striatal neuronal circuit architecture by which a recent history of chronic stress disrupts the action-outcome learning underlying adaptive agency and promotes the formation of inflexible habits. We found that the projection from the basolateral amygdala to the dorsomedial striatum is activated by rewarding events to support the action-outcome learning needed for flexible, goal-directed decision-making. Chronic stress attenuates this to disrupt action-outcome learning and, therefore, agency. Conversely, the projection from the central amygdala to the dorsomedial striatum mediates habit formation. Following stress, this pathway is progressively recruited to learning to promote the premature formation of inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to disrupt agency and promote habit. These data provide neuronal circuit insights into how chronic stress shapes learning and decision-making, and help understanding of how stress can lead to the disrupted decision-making and pathological habits that characterize substance use disorders and mental health conditions
Dichotomy or continuum? A global review of the interaction between autonomous and planned adaptations
No full textAdaptation to climate change is often conceptualized as a dichotomy, with responses being either planned (formal and structured) or autonomous (organic and self-organized, often known as “everyday adaptation”). Recent literature on adaptation responses has highlighted the existence and importance of the interplay between autonomous and planned adaptation, but examination of this interaction has been limited to date. We use a global database of 1682 peer-reviewed articles on adaptation responses to systematically examine autonomous and planned adaptations, with an emphasis on how these types of adaptations interact with one another. We propose a third category, mixed adaptation, which demonstrates characteristics of both autonomous and planned types, and which recognizes nuances in how organization, external support, formality, and autonomy manifest in the fuzzy space between the two. We find that more than one-third of articles reporting on adaptation responses fall into this mixed category, with cases across sectors and world regions. We develop a qualitative typology of mixed adaptation that identifies nine ways that autonomous and planned adaptation interact and influence each other both positively and negatively. Based on these findings, we argue for more nuanced examinations of the interplay between autonomous and planned adaptation and for conceptualizing adaptation planning as a continuum between the two rather than a dichotomy. Exploring the patterns of interplay from a large database of adaptation responses offers new insights on the relative roles of both autonomous and planned adaptation for mobilizing adaptation pathways in locally relevant, scalable, effective, and equitable ways
Addressing the Growing Intersectionality of Cancer and Heart Disease: The Rise of Cardio-Oncology
Get PDFChronic, Low-Dose Methamphetamine Reveals Sexual Dimorphism of Memory Performance, Histopathology, and Gene Expression Affected by HIV-1 Tat Protein in a Transgenic Model of NeuroHIV
Get PDFMethamphetamine (METH) use is frequent among people with HIV (PWH) and appears to increase the risk of neuronal injury and neurocognitive impairment (NCI). This study explored in vivo the effects of a 12 week (long-term), low-dose METH regimen in a transgenic animal model of neuroHIV with inducible expression of HIV-1 transactivator of transcription (Tat). Seven months after transient Tat induction and five months after METH exposure ended, we detected behavioral changes in the Barnes maze (BM) spatial memory task in the Tat and METH groups but not the combined Tat + METH group. The novel object recognition (NOR) task revealed that Tat extinguished discrimination in female animals with and without METH, although METH alone slightly improved NOR. In contrast, in males, Tat, METH, and Tat + METH all compromised NOR. Neuropathological examination detected sex-dependent and brain region-specific changes of pre-synaptic terminals, neurites, and activation of astrocytes and microglia. RNA-sequencing and quantitative reverse transcription polymerase chain reaction indicated that METH and Tat significantly altered gene expression, including factors linked to Alzheimer's disease-like NCI. In summary, chronic low-dose METH exerts long-term effects on behavioral function, neuropathology, and mRNA expression, and modulates the effects of Tat, suggesting sex-dependent and -independent mechanisms may converge in HIV brain injury and NCI
Increasing vulnerability of an endemic Mediterranean-climate conifer to changing climate and fire regime
Get PDFConifer species of Mediterranean-type ecosystems (MTEs) are especially sensitive to coupled changes in climate and fire regime. Recently California’s MTE conifers have experienced elevated mortality, range shifts, and decreased abundance relative to broadleaf trees. Restricted-range species may be especially vulnerable to environmental change and are a high priority for climate change assessment and adaptation management. We used species distribution modeling and wildfire probability models to assess the potential vulnerability of Pseudotsuga macrocarpa (Bigcone Douglas fir, hereafter BDF), a restricted-range conifer of southern California mountains that is a species of concern because of its ecological importance and recent mortality due to drought and wildfire. We also modeled the distribution of Quercus chrysolepis (CLO), a widespread oak that can be co-dominant with BDF and that can limit fire spread and reduce crown fire risk to BDF compared to the risk from surrounding chaparral vegetation. Ensembles of MAXENT and General Boosted Models were produced for a 2.1 million ha model domain encompassing BDF’s 672,000 ha range for the period 1981–2010, and were projected to 2040–2069 and 2070–2099 using three climate models (warmer-wetter, warmer, and hotter-drier) under a high emission scenario (IPCC 5th Assessment, RCP 8.5). Wildfire projections were analyzed only for mid-century based on warmer-wetter and hotter-drier climate scenarios. Our analysis contributes several important new insights: (1) topoclimatic habitat for BDF could shrink by 19–57% by mid-century, especially for southernmost populations; (2) by mid-century, wildfire probability could increase 2–4 fold in BDF habitat, potentially diminishing the value of mid-to-high elevation sites as topoclimatic refugia; (3) CLO could play a diminishing role in providing refuge from severe wildfires as soon as mid-century but especially by end-of-century; (4) extensive areas of stable mid-century and late-century habitat are confined to national forests in the San Gabriel Mountains and Transverse Ranges. The climate and fire vulnerability of BDF could be reduced by management actions such as mechanical fuel treatments and post-fire restoration, but these are highly constrained by topography, access, and sensitive wildlife species. Our case study illustrates the rapidly increasing vulnerability of endemic conifer species in MTE forests
Genome‐wide association studies on resistance to powdery mildew in cultivated emmer wheat
Get PDFPowdery mildew, caused by the fungal pathogen Blumeria graminis (DC.) E. O. Speer f. sp. tritici Em. Marchal (Bgt), is a constant threat to global wheat (Triticum aestivum L.) production. Although ∼100 powdery mildew (Pm) resistance genes and alleles have been identified in wheat and its relatives, more is needed to minimize Bgt's fast evolving virulence. In tetraploid wheat (Triticum turgidum L.), wild emmer wheat [T. turgidum ssp. dicoccoides (Körn. ex Asch. & Graebn.) Thell.] accessions from Israel have contributed many Pm resistance genes. However, the diverse genetic reservoirs of cultivated emmer wheat [T. turgidum ssp. dicoccum (Schrank ex Schübl.) Thell.] have not been fully exploited. In the present study, we evaluated a diverse panel of 174 cultivated emmer accessions for their reaction to Bgt isolate OKS(14)-B-3-1 and found that 66% of accessions, particularly those of Ethiopian (30.5%) and Indian (6.3%) origins, exhibited high resistance. To determine the genetic basis of Bgt resistance in the panel, genome-wide association studies were performed using 46,383 single nucleotide polymorphisms (SNPs) from genotype-by-sequencing and 4331 SNPs from the 9K SNP Infinium array. Twenty-five significant SNP markers were identified to be associated with Bgt resistance, of which 21 SNPs are likely novel loci, whereas four possibly represent emmer derived Pm4a, Pm5a, PmG16, and Pm64. Most novel loci exhibited minor effects, whereas three novel loci on chromosome arms 2AS, 3BS, and 5AL had major effect on the phenotypic variance. This study demonstrates cultivated emmer as a rich source of powdery mildew resistance, and the resistant accessions and novel loci found herein can be utilized in wheat breeding programs to enhance Bgt resistance in wheat
Differing genetics of saline and cocaine self-administration in the hybrid mouse diversity panel
Get PDFTo identify genes that regulate the response to the potentially addictive drug cocaine, we performed a control experiment using genome-wide association studies (GWASs) and RNA-Seq of a panel of inbred and recombinant inbred mice undergoing intravenous self-administration of saline. A linear mixed model increased statistical power for analysis of the longitudinal behavioral data, which was acquired over 10 days. A total of 145 loci were identified for saline compared to 17 for the corresponding cocaine GWAS. Only one locus overlapped. Transcriptome-wide association studies (TWASs) using RNA-Seq data from the nucleus accumbens and medial frontal cortex identified 5031434O11Rik and Zfp60 as significant for saline self-administration. Two other genes, Myh4 and Npc1, were nominated based on proximity to loci for multiple endpoints or a cis locus regulating expression. All four genes have previously been implicated in locomotor activity, despite the absence of a strong relationship between saline taking and distance traveled in the open field. Our results indicate a distinct genetic basis for saline and cocaine self-administration, and suggest some common genes for saline self-administration and locomotor activity
Naturally disengaging control to reveal habits.
No full textHabits are an essential part of everyday decision-making. However, the mechanisms underlying habit formation and expression in humans are difficult to study in the laboratory, owing to a dearth of convenient experimental paradigms that reliably exhibit a key marker of habits - training-induced inflexibility - under ecologically valid conditions. This difficulty is often attributed to the fact that habits are identified in contrast to goal-directed (GD) control, which research participants typically engage strongly in laboratory experiments. To address this gap, we develop a new, short habit learning paradigm that incorporates several features we hypothesized would encourage participants to disengage GD control, enabling habits to exert greater influence over behavior: a hierarchical multi-step trial structure, opportunities for self-correction, and frequent switches between extensively and moderately practiced behaviors. Through a series of experiments, we demonstrate that overtraining amplifies habitual control, as evidenced by errors biased toward the overtrained context and away from the moderately-trained context at early response times, while later responses remain dominated by GD control. The reliability of this overtraining effect depended on the inclusion of task features designed to dampen GD control. In addition to providing a practical, robust, and flexible tool for studying the cognitive processes underlying habit formation and habitual control, our paradigm moves us beyond the traditional stimulus-response conception of habits, expanding the definition to include more complex, hierarchical behaviors that better reflect naturalistic human habits
