The Corticostriatal System in Dissociated Cell Culture

The sparse connectivity within the striatum in vivo makes the investigation of individual corticostriatal synapses very difficult. Most studies of the corticostriatal input have been done using electrical stimulation under conditions where it is hard to identify the precise origin of the cortical input. We have employed an in vitro dissociated cell culture system that allows the identification of individual corticostriatal pairs and have been developing methods to study individual neuron inputs to striatal neurons. In mixed corticostriatal cultures, neurons had resting activity similar to the system in vivo. Up/down states were obvious and seemed to encompass the entire culture. Mixed cultures of cortical neurons from transgenic mice expressing green fluorescent protein with striatal neurons from wild-type mice of the same developmental stage allowed visual identification of individual candidate corticostriatal pairs. Recordings were performed between 12 and 37 days in vitro (DIV). To investigate synaptic connections we recorded from 69 corticostriatal pairs of which 44 were connected in one direction and 25 reciprocally. Of these connections 41 were corticostriatal (nine inhibitory) and 53 striatocortical (all inhibitory). The observed excitatory responses were of variable amplitude (−10 to −370 pA, n = 32). We found the connections very secure – with negligible failures on repeated stimulation (approximately 1 Hz) of the cortical neuron. Inhibitory corticostriatal responses were also observed (−13 to −314 pA, n = 9). Possibly due to the mixed type of culture we found an inhibitory striatocortical response (−14 to −598 pA, n = 53). We are now recording from neurons in separate compartments to more closely emulate neuroanatomical conditions but still with the possibility of the easier identification of the connectivity

Striatal bilateral control of skilled forelimb movement

Skilled motor behavior requires bihemispheric coordination, and participation of striatal outputs originating from two neuronal groups identified by distinctive expression of D1 or D2 dopamine receptors. We trained mice to reach for and grasp a single food pellet and determined how the output pathways differently affected forelimb trajectory and task efficiency. We found that inhibition and excitation of D1-expressing spiny projection neurons (D1SPNs) have a similar effect on kinematics results, as if excitation and inhibition disrupt the whole ensemble dynamics and not exclusively one kind of output. In contrast, D2SPNs participate in control of target accuracy. Further, ex vivo electrophysiological comparison of naive mice and mice exposed to the task showed stronger striatal neuronal connectivity for ipsilateral D1 and contralateral D2 neurons in relation to the paw used. In summary, while the output pathways work together to smoothly execute skill movements, practice of the movement itself changes synaptic patterns.journal articl

Health and climate related ecosystem services provided by street trees in the urban environment

Published onlineJournal ArticleUrban tree planting initiatives are being actively promoted as a planning tool to enable urban areas to adapt to and mitigate against climate change, enhance urban sustainability and improve human health and well-being. However, opportunities for creating new areas of green space within cities are often limited and tree planting initiatives may be constrained to kerbside locations. At this scale, the net impact of trees on human health and the local environment is less clear, and generalised approaches for evaluating their impact are not well developed.In this review, we use an urban ecosystems services framework to evaluate the direct, and locally-generated, ecosystems services and disservices provided by street trees. We focus our review on the services of major importance to human health and well-being which include 'climate regulation', 'air quality regulation' and 'aesthetics and cultural services'. These are themes that are commonly used to justify new street tree or street tree retention initiatives. We argue that current scientific understanding of the impact of street trees on human health and the urban environment has been limited by predominantly regional-scale reductionist approaches which consider vegetation generally and/or single out individual services or impacts without considering the wider synergistic impacts of street trees on urban ecosystems. This can lead planners and policymakers towards decision making based on single parameter optimisation strategies which may be problematic when a single intervention offers different outcomes and has multiple effects and potential trade-offs in different places.We suggest that a holistic approach is required to evaluate the services and disservices provided by street trees at different scales. We provide information to guide decision makers and planners in their attempts to evaluate the value of vegetation in their local setting. We show that by ensuring that the specific aim of the intervention, the scale of the desired biophysical effect and an awareness of a range of impacts guide the choice of i) tree species, ii) location and iii) density of tree placement, street trees can be an important tool for urban planners and designers in developing resilient and resourceful cities in an era of climatic change

Sexual selection protects against extinction

Reproduction through sex carries substantial costs, mainly because only half of sexual adults produce offspring. It has been theorised that these costs could be countered if sex allows sexual selection to clear the universal fitness constraint of mutation load. Under sexual selection, competition between (usually) males, and mate choice by (usually) females create important intraspecific filters for reproductive success, so that only a subset of males gains paternity. If reproductive success under sexual selection is dependent on individual condition, which depends on mutation load, then sexually selected filtering through ‘genic capture’ could offset the costs of sex because it provides genetic benefits to populations. Here, we test this theory experimentally by comparing whether populations with histories of strong versus weak sexual selection purge mutation load and resist extinction differently. After evolving replicate populations of the flour beetle Tribolium castaneum for ~7 years under conditions that differed solely in the strengths of sexual selection, we revealed mutation load using inbreeding. Lineages from populations that had previously experienced strong sexual selection were resilient to extinction and maintained fitness under inbreeding, with some families continuing to survive after 20 generations of sib × sib mating. By contrast, lineages derived from populations that experienced weak or non-existent sexual selection showed rapid fitness declines under inbreeding, and all were extinct after generation 10. Multiple mutations across the genome with individually small effects can be difficult to clear, yet sum to a significant fitness load; our findings reveal that sexual selection reduces this load, improving population viability in the face of genetic stress

Cell envelope proteins of Staphylococcus epidermidis grown in vivo in a peritoneal chamber implant

Staphylococcus epidermidis was grown in vivo in chambers implanted intraperitoneally in rats. The cell wall and cytoplasmic membrane protein profiles of the in vivo-grown organisms were compared with those of S. epidermidis grown in vitro in nutrient broth (NB), in iron-restricted NB, or in pooled human peritoneal dialysate (HPD). Compared with growth in broth and in common with growth in HPD, growth in vivo in chambers resulted in the repression of many S. epidermidis wall proteins, with proteins of 27, 42, 54, and 70 kDa predominating. Growth in vivo also resulted in the induction of two iron-repressible cytoplasmic membrane proteins of 32 and 36 kDa, which were also present in staphylococci grown in HPD and in iron-restricted NB. Immunoblotting experiments revealed that in sera taken 21 days after inoculation of the intraperitoneal chambers, the predominant antibody response to cell envelope proteins was directed against the 32- and 36-kDa iron-repressible membrane proteins

How consistent are the transcriptome changes associated with cold acclimation in two species of the Drosophila virilis group?

This work was financially support by a Marie Curie Initial Training Network grant, “Understanding the evolutionary origin of biological diversity” (ITN-2008–213780 SPECIATION), grants from the Academy of Finland to A.H. (project 132619) and M.K. (projects 268214 and 272927), a grant from NERC, UK to M.G.R. (grant NE/J020818/1), and NERC, UK PhD studentship to D.J.P. (NE/I528634/1).For many organisms the ability to cold acclimate with the onset of seasonal cold has major implications for their fitness. In insects, where this ability is widespread, the physiological changes associated with increased cold tolerance have been well studied. Despite this, little work has been done to trace changes in gene expression during cold acclimation that lead to an increase in cold tolerance. We used an RNA-Seq approach to investigate this in two species of the Drosophila virilis group. We found that the majority of genes that are differentially expressed during cold acclimation differ between the two species. Despite this, the biological processes associated with the differentially expressed genes were broadly similar in the two species. These included: metabolism, cell membrane composition, and circadian rhythms, which are largely consistent with previous work on cold acclimation/cold tolerance. In addition, we also found evidence of the involvement of the rhodopsin pathway in cold acclimation, a pathway that has been recently linked to thermotaxis. Interestingly, we found no evidence of differential expression of stress genes implying that long-term cold acclimation and short-term stress response may have a different physiological basis.PostprintPeer reviewe

Clinical peripherality: development of a peripherality index for rural health services

BACKGROUND: The configuration of rural health services is influenced by geography. Rural health practitioners provide a broader range of services to smaller populations scattered over wider areas or more difficult terrain than their urban counterparts. This has implications for training and quality assurance of outcomes. This exploratory study describes the development of a "clinical peripherality" indicator that has potential application to remote and rural general practice communities for planning and research purposes. METHODS: Profiles of general practice communities in Scotland were created from a variety of public data sources. Four candidate variables were chosen that described demographic and geographic characteristics of each practice: population density, number of patients on the practice list, travel time to nearest specialist led hospital and travel time to Health Board administrative headquarters. A clinical peripherality index, based on these variables, was derived using factor analysis. Relationships between the clinical peripherality index and services offered by the practices and the staff profile of the practices were explored in a series of univariate analyses. RESULTS: Factor analysis on the four candidate variables yielded a robust one-factor solution explaining 75% variance with factor loadings ranging from 0.83 to 0.89. Rural and remote areas had higher median values and a greater scatter of clinical peripherality indices among their practices than an urban comparison area. The range of services offered and the profile of staffing of practices was associated with the peripherality index. CONCLUSION: Clinical peripherality is determined by the nature of the practice and its location relative to secondary care and administrative and educational facilities. It has features of both gravity model-based and travel time/accessibility indicators and has the potential to be applied to training of staff for rural and remote locations and to other aspects of health policy and planning. It may assist planners in conceptualising the effects on general practices of centralising specialist clinical services or administrative and educational facilities

Executive function and intelligence in the resolution of temporary syntactic ambiguity: An individual differences investigation

In the current study, we examined the role of intelligence and executive functions in the resolution of temporary syntactic ambiguity using an individual differences approach. Data were collected from 174 adolescents and adults who completed a battery of cognitive tests as well as a sentence comprehension task. The critical items for the comprehension task consisted of object/subject garden paths (e.g. While Anna dressed the baby that was small and cute played in the crib.), and participants answered a comprehension question (e.g. Did Anna dress the baby?) following each one. Previous studies have shown that garden-path misinterpretations tend to persist into final interpretations. Results showed that both intelligence and processing speed interacted with ambiguity. Individuals with higher intelligence and faster processing were more likely to answer the comprehension questions correctly, and specifically, following ambiguous as opposed to unambiguous sentences. Inhibition produced a marginal effect, but the variance in inhibition was largely shared with intelligence. Conclusions focus on the role of individual differences in cognitive ability and their impact on syntactic ambiguity resolution

Forensic child and Adolescent Psychiatry and mental health in Europe

Background When faced with the discovery of their child’s self-harm, mothers and fathers may re-evaluate their parenting strategies. This can include changes to the amount of support they provide their child and changes to the degree to which they control and monitor their child. Methods We conducted an in-depth qualitative study with 37 parents of young people who had self-harmed in which we explored how and why their parenting changed after the discovery of self-harm. Results Early on, parents often found themselves “walking on eggshells” so as not to upset their child, but later they felt more able to take some control. Parents’ reactions to the self-harm often depended on how they conceptualised it: as part of adolescence, as a mental health issue or as “naughty behaviour”. Parenting of other children in the family could also be affected, with parents worrying about less of their time being available for siblings. Many parents developed specific strategies they felt helped them to be more effective parents, such as learning to avoid blaming themselves or their child for the self-harm and developing new ways to communicate with their child. Parents were generally eager to pass their knowledge on to other people in the same situation. Conclusions Parents reported changes in their parenting behaviours after the discovery of a child’s self-harm. Professionals involved in the care of young people who self-harm might use this information in supporting and advising parents.</p