Role for Midbrain Glutamatergic and Epithalamic Circuitry in Stress Induced Behavioral Changes and Motivation

The Ventral Tegmental Area (VTA) is an evolutionarily conserved midbrain region that is critical for reinforcement learning and motivated behavior. The cellular heterogeneity of the VTA creates an opportunity to evaluate how genetically distinct neuronal populations and circuits inform motivation. The experiments within this thesis evaluate the role of glutamatergic neurons, VGluT2+, within the realms of both natural and drug seeking (oxycodone) behavior, aversion, and stress resilience. In-vivo viral monitoring and manipulation strategies (optogenetics, chemogenetics, and fiber photometry) were leveraged to record the unique neurochemical signaling dynamics of this population during motivated action and establish the causal behavioral contributions of this population and its epithalamic efferents. Within Pavlovian reward and aversion unique GABAergic and glutamatergic signaling input to these neurons was recorded for conditioned behavioral predictors (cues) and their associated outcomes. Significant changes in intracellular calcium signaling, required for vesicular release, were recorded for the same behavioral epochs as well as drug associated cues and oral oxycodone administration. Global inhibition of this VGluT2+ population, using hM4Di, prevented drug reinstatement behavior in male mice. In addition to natural and drug seeking behavior VTA VGluT2+ neurons were significantly recruited by stress experience and directly regulated non-associative behavioral changes, such as reduced social engagement. VTA VGluT2+ inhibition during stress prevented the development of recorded behavioral deficits. Genetically distinct VTA VGluT2+ neurons were recruited by stress experience and these stress responsive neurons established dense outputs to the lateral habenula (LHb). Neurochemical signaling in this epithalamic nucleus was recorded during stress and VTA &agrave; LHb circuitry was inhibited to determine the causal role of this pathway. Blocking neurochemical output within this neuronal circuit facilitated resilience and prevented behavioral changes in motivation following stress. These foundational experiments establish clear roles for VTA VGluT2+ in diverse motivated behaviors, while critically monitoring how neurochemical signaling dynamics and circuits contribute to these behaviors.</p

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Analysis of high-identity segmental duplications in the grapevine genome

<p>Abstract</p> <p>Background</p> <p>Segmental duplications (SDs) are blocks of genomic sequence of 1-200 kb that map to different loci in a genome and share a sequence identity > 90%. SDs show at the sequence level the same characteristics as other regions of the human genome: they contain both high-copy repeats and gene sequences. SDs play an important role in genome plasticity by creating new genes and modeling genome structure. Although data is plentiful for mammals, not much was known about the representation of SDs in plant genomes. In this regard, we performed a genome-wide analysis of high-identity SDs on the sequenced grapevine (<it>Vitis vinifera</it>) genome (PN40024).</p> <p>Results</p> <p>We demonstrate that recent SDs (> 94% identity and >= 10 kb in size) are a relevant component of the grapevine genome (85 Mb, 17% of the genome sequence). We detected mitochondrial and plastid DNA and genes (10% of gene annotation) in segmentally duplicated regions of the nuclear genome. In particular, the nine highest copy number genes have a copy in either or both organelle genomes. Further we showed that several duplicated genes take part in the biosynthesis of compounds involved in plant response to environmental stress.</p> <p>Conclusions</p> <p>These data show the great influence of SDs and organelle DNA transfers in modeling the <it>Vitis vinifera </it>nuclear DNA structure as well as the impact of SDs in contributing to the adaptive capacity of grapevine and the nutritional content of grape products through genome variation. This study represents a step forward in the full characterization of duplicated genes important for grapevine cultural needs and human health.</p

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Ventral tegmental area glutamate neurons establish a mu-opioid receptor gated circuit to mesolimbic dopamine neurons and regulate opioid-seeking behavior

A two-neuron model of ventral tegmental area (VTA) opioid function classically involves VTA GABA neuron regulation of VTA dopamine neurons via a mu-opioid receptor dependent inhibitory circuit. However, this model predates the discovery of a third major type of neuron in the VTA: glutamatergic neurons. We found that about one-quarter of VTA neurons expressing the mu-opioid receptor are glutamate neurons without molecular markers of GABA co-release. Glutamate-Mu opioid receptor neurons are largely distributed in the anterior VTA. The majority of remaining VTA mu-opioid receptor neurons are GABAergic neurons that are mostly within the posterior VTA and do not express molecular markers of glutamate co-release. Optogenetic stimulation of VTA glutamate neurons resulted in excitatory currents recorded from VTA dopamine neurons that were reduced by presynaptic activation of the mu-opioid receptor ex vivo, establishing a local mu-opioid receptor dependent excitatory circuit from VTA glutamate neurons to VTA dopamine neurons. This VTA glutamate to VTA dopamine pathway regulated dopamine release to the nucleus accumbens through mu-opioid receptor activity in vivo. Behaviorally, VTA glutamate calcium-related neuronal activity increased following oral oxycodone consumption during self-administration and response-contingent oxycodone-associated cues during abstinent reinstatement of drug-seeking behavior. Further, chemogenetic inhibition of VTA glutamate neurons reduced abstinent oral oxycodone-seeking behavior in male but not female mice. These results establish 1) a three-neuron model of VTA opioid function involving a mu-opioid receptor gated VTA glutamate neuron pathway to VTA dopamine neurons that controls dopamine release within the nucleus accumbens, and 2) that VTA glutamate neurons participate in opioid-seeking behavior

Impact of Adjunct Testosterone on Cancer-Related Fatigue: An Ancillary Analysis from a Controlled Randomized Trial

Many cancer patients undergoing treatment experience cancer-related fatigue (CRF). Inflammatory markers are correlated with CRF but are not routinely targeted for treatment. We previously demonstrated in an NIH-funded placebo-controlled, double-blind, randomized clinical trial (NCT00878995, closed to follow-up) that seven weekly injections of 100 mg adjunct testosterone preserved lean body mass in cancer patients undergoing standard-of-care treatment in a hospital setting. Because testosterone therapy can reduce circulating proinflammatory cytokines, we conducted an ancillary analysis to determine if this testosterone treatment reduced inflammatory burden and improved CRF symptoms and health-related quality of life. Randomization was computer-generated and managed by the pharmacy, which dispensed testosterone and placebo in opaque syringes to the administering study personnel. A total of 24 patients were randomized (14 placebo, 10 testosterone), and 21 were included in the primary analysis (11 placebo, 10 testosterone). Testosterone therapy did not ameliorate CRF symptoms (placebo to testosterone difference in predicted mean multidimensional fatigue symptom inventory scores: −5.6, 95% CI: −24.6 to 13.3), improve inflammatory markers, or preserve health-related quality of life and functional measures of performance in late-stage cancer patients

Nocturnal basking in freshwater turtles: A global assessment

Diurnal basking (“sunning”) is common in many ectotherms and is generally thought to be a behavioural mechanism for thermoregulation. Recent studies have reported the occurrence of nocturnal basking in a few distantly-related species of freshwater turtles, but the true extent of this behaviour is unknown, and it may be underreported due to sampling biases (e.g., not surveying for turtles at night). Therefore, we initiated a global, collaborative effort to systematically document and quantify basking activity (diurnal and nocturnal) across a wide range of freshwater turtle species and locations. We conducted camera trap or manual surveys in North America, the Caribbean, Europe, Asia, Africa, the Seychelles, and Australia. We collected 873,111 trail camera photographs (25,273 hrs of search effort) and obtained data on 29 freshwater turtle species from seven families. Nocturnal basking was documented in 13 species, representing six families (Chelidae, Emydidae, Geoemydidae, Kinosternidae, Pelomedusidae, and Trionychidae), including representatives in Central America, Trinidad and Tobago, Africa, the Seychelles, Asia, and Australia. Nocturnal basking was restricted to tropical and sub-tropical locations, suggesting that environmental temperature plays a role in this behaviour. However, the primary factors driving nocturnal basking are yet to be determined and may vary geographically and by species. The frequency and duration of nocturnal basking varied among species and seasons, but nocturnal basking events were often substantially longer than diurnal events. This is the first study to document a widespread occurrence of nocturnal basking, and our results suggest that nocturnal basking may be a common, although overlooked, aspect of many species’ ecology

Designing, formalizing and evaluating a flexible architecture for integrated service delivery: Combining event-driven and service-oriented architectures

An in?ux of service providers collaborate in networks to meet their clients’ demands. Integrated service delivery (ISD) is a way to let networked service providers offer services to their clients by bundling selected services offered by each provider so that clients do not have to deal with each single provider anymore. Designing such a network is a complicated endeavor as independent organizations need to collaborate and should understand how their activities are dependent on each other. Communication of events is necessary to deal with unpredictable and complex processes in such a network. In contrast with conventional event-driven architecture and service-oriented architecture (SOA) approaches, the hybrid model of event-driven interactions and SOA offers the required ?exibility to realize ISD. This ?exibility is realized by integrating not only services but also the processes of the different service providers to supply such services. A design science approach has been applied resulting in a detailed and formalized design of an eventdriven service-oriented architecture (EDSOA). The EDSOA has been illustrated to show how ISD is realized with support of the architecture in a scenario concerning an application for a temporary residence permit by an immigrant. An evaluative workshop has been conducted which re?ected that the following criteria are most important for successful organizational adoption of the EDSOA: expected usefulness, ?t with organizational standards, use of trusted technology, and ease of maintenance.ISSTechnology, Policy and Managemen