Microglia have crucial roles in sculpting synapses and maintaining neural circuits during development. To test the hypothesis that microglia continue to regulate neural circuit connectivity in adult ...brain, we have investigated the effects of chronic microglial depletion, via CSF1R inhibition, on synaptic connectivity in the visual cortex in adult mice of both sexes. We find that the absence of microglia dramatically increases both excitatory and inhibitory synaptic connections to excitatory cortical neurons assessed with functional circuit mapping experiments in acutely prepared adult brain slices. Microglia depletion leads to increased densities and intensities of perineuronal nets. Furthermore,
calcium imaging across large populations of visual cortical neurons reveals enhanced neural activities of both excitatory neurons and parvalbumin-expressing interneurons in the visual cortex following microglia depletion. These changes recover following adult microglia repopulation. In summary, our new results demonstrate a prominent role of microglia in sculpting neuronal circuit connectivity and regulating subsequent functional activity in adult cortex.
Microglia are the primary immune cell of the brain, but recent evidence supports that microglia play an important role in synaptic sculpting during development. However, it remains unknown whether and how microglia regulate synaptic connectivity in adult brain. Our present work shows chronic microglia depletion in adult visual cortex induces robust increases in perineuronal nets, and enhances local excitatory and inhibitory circuit connectivity to excitatory neurons. Microglia depletion increases
neural activities of both excitatory neurons and parvalbumin inhibitory neurons. Our new results reveal new potential avenues to modulate adult neural plasticity by microglia manipulation to better treat brain disorders, such as Alzheimer's disease.
Peer Mentoring schemes tend to be developed as retention strategies, however, they can also serve other purposes (psychosocial or career‐related). However, evidence of the effectiveness of these ...presents mixed results and less is known about the horizontal peer support schemes which may help students capitalize on existing peer relationships. We developed an integrated learning communities (ILC) peer support scheme, building on the theoretical principles of social identity theory, which we embedded within our existing teaching framework and designed functional activities. Collective activities were undertaken to promote the processes of social identity with the intention that these may foster social and academic integration experiences. This intervention was undertaken with an entire cohort of first year undergraduate psychology students. We conducted semi‐structured interviews with a self‐selected sample of these students (N = 17). Thematic analysis revealed two main themes, each with two sub‐themes. These were: “Divergent Experiences” with the sub‐themes of “dependent on people” and “types of support”, and “Good idea in principle” with the sub‐themes of “Theory ≠ Practice” and “Dependent on student engagement”. Although identifying with a peer group was not transparent in the interviews, the existence of a peer support scheme was perceived positively by students which might explain the success of the newly developed student‐led Psychology Society. Indeed, this Psychology Society can provide a lasting framework for further amplification of the student voice. We conclude that our embedded ILC was both feasible and potentially valuable, but it is crucial for the peer support approach to have transactional significance.
With respect to supporting student well-being and success, the current research developed a peer support scheme, built on the principles of Social Identity Theory (SIT). This was targeted towards ...first year undergraduate psychology students, in which measures of collective identity, sense of belonging, group efficacy, happiness and resilience were obtained, along with attendance and academic attainment. Following one academic year of being part of our peer support scheme, participants (N = 90) completed a questionnaire and consented to their attendance and attainment data to be used. It was found that students' collective identity was positively related to their sense of belonging, group efficacy beliefs and happiness. Further, the sense of belonging was a reliable predictor of happiness, but not attendance or academic attainment. Therefore, there is some evidence to suggest that an SIT-driven peer support scheme can support students' psychosocial well-being, although more is needed to ascertain whether this could be developed further to observe any course-related outcomes. Theoretical contributions to SIT are therefore presented, in which the insights can be applied to Higher Education beyond the UK.
Non-volatile superbased-derived protic ionic liquids are thermally stable and highly conductive, thus hold great promises for electrochemical applications. However, systematic accounts of their ...electrochemical properties are yet to be established. In this contribution, five hydrophobic superbase-derived protic ionic liquids (PILs) have been prepared from Brønsted superbases and the salts of strong acids, and their decomposition temperature, density, conductivity and viscosity have been measured. The greatest viscosity was observed with the superbased PILs, MTBDHNfO (2212 cP) and the least with MTBDHNTf2 (121 cP). Greatest conductivity was measured for MTBDHNTf2 (1.54 mS cm−1) and the least for MTBDHNfO (0.089 mS cm−1). By combining density, conductivity and viscosity, a Walden plot was set up to demonstrate the degree of ionization, or ‘ionicity’ of each of the five PILs is greater than 10%. Their electrochemical characteristics were determined using cyclic voltammetry. Two IUPAC-recommended internal potential reference systems, ferrocene/ferrocenium and cobaltocenium/cobaltocene, were assessed for use in the five PILs. Potential windows of the five PILs were established at glassy carbon, gold and platinum electrodes, where the widest potential window was observed with glassy carbon electrodes with no direct correlation found between the ΔpKa values and the potential windows. The widest potential window was measured in MTBHbeti (4.3 ± 0.1 V) and the shortest in HNC(dma)Hbeti (2.7 ± 0.1 V). The double layer capacitance was also investigated for potential applications in supercapacitors.
Inhibitory interneurons are crucial to brain function and their dysfunction is implicated in neuropsychiatric conditions. Emerging evidence indicates that cholecystokinin (CCK)-expressing ...interneurons (CCK+) are highly heterogenous. We find that a large subset of parvalbumin-expressing (PV+) interneurons express CCK strongly; between 40 and 56% of PV+ interneurons in mouse hippocampal CA1 express CCK. Primate interneurons also exhibit substantial PV/CCK co-expression. Mouse PV+/CCK+ and PV+/CCK- cells show distinguishable electrophysiological and molecular characteristics. Analysis of single nuclei RNA-seq and ATAC-seq data shows that PV+/CCK+ cells are a subset of PV+ cells, not of synuclein gamma positive (SNCG+) cells, and that they strongly express oxidative phosphorylation (OXPHOS) genes. We find that mitochondrial complex I and IV-associated OXPHOS gene expression is strongly correlated with CCK expression in PV+ interneurons at both the transcriptomic and protein levels. Both PV+ interneurons and dysregulation of OXPHOS processes are implicated in neuropsychiatric conditions, including autism spectrum (ASD) disorder and schizophrenia (SCZ). Analysis of human brain samples from patients with these conditions shows alterations in OXPHOS gene expression. Together these data reveal important molecular characteristics of PV-CCK co-expressing interneurons and support their implication in neuropsychiatric conditions.
Many energy conversion technologies comprise proton-coupled electron transfer reactions that consume/produce protons at electrode surfaces, thereby generating interfacial pH environments that differ ...substantially from the bulk. Quantification of these interfacial pH swings is a prerequisite for designing efficient energy conversion systems. Herein, we develop a methodology for quantifying interfacial pH using open circuit potential (OCP) transients. Using a model system of hydrogen evolution on Pt, we quantify polarization-induced pH swings under a wide variety of conditions relevant for functional devices. We find that even strongly buffered solutions experience pH swings of >2 pH units at modest current densities of −30 mA cm−2. The interfacial pH swings are augmented by the addition of supporting electrolyte and the presence of Nafion polymer overlayers—resulting in swings >12 pH units. Analytical transport modeling validates the developed methodology and enables quantitative prediction of both steady-state and transient interfacial pH swings.
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•Open circuit potential decay transients can quantify interfacial pH swings•Even strongly buffered solutions experience pH swings of >2 pH units•pH swing is enhanced by the presence of Nafion polymer overlayers•Transport modeling enables quantitative prediction of transient pH swing
The local proton activity at electrode-solution interfaces plays a major role in determining efficiencies of technologically relevant electrocatalytic transformations, including hydrogen evolution/oxidation, oxygen evolution/reduction, and carbon dioxide reduction. Since each of these electrochemical reactions necessarily consumes or produces protons, the interfacial proton activity is commonly profoundly different, compared with the bulk solution during active electrolysis. Understanding the underlying factors that influence polarization-induced interfacial pH swing is therefore essential for designing next-generation electrolyzers. To this end, we developed a technique that measures interfacial pH swing on complex gas diffusion electrodes and is uniquely amenable to high current conditions relevant in functional electrolyzer devices. Our study emphasizes the propensity of high current densities to induce dramatic deviations in pH between the electrode-solution interface and bulk solution.
The pH at an electrode’s surface strongly affects its reactivity and efficiency for different reactions. Furthermore, the pH can change as a result of electrocatalysis and is very difficult to measure in such a scenario. Herein, we develop a methodology for quantifying interfacial pH using open circuit potential (OCP) transients. Using a model system of hydrogen evolution on Pt, we quantify polarization-induced pH swings for a diverse range of conditions pertinent to functional devices.
Manufacturing Message Specification (MMS) is an international standard for shop floor machine control. It defines a set of conceptual schema and an interactive software object known as Virtual ...Manufacturing Device (VMD). Many systems have been established using this protocol but very few formal methods have been used to build such systems. This paper addresses the problems of the design and analysis of a network-based task oriented messaging system for flexible robot task control using a Petri net. The information and message transfer processes of the MMS systems were analysed. The modelling methodology allows a top down approach by which the net model is decomposed into fine details with clear identification of components which can be realised directly from the model. This approach is illustrated in this paper by a Windows-based robot control prototype system implemented from the Petri net model. The prototype was built using Object Windows Library and the NetBIOS session layer protocol on a PC network.
Heterogeneous electrocatalysis involves elementary chemical and charge transfer reaction steps, with the kinetics of each step contributing to the overpotential requirement at a given reaction rate. ...Typical experiments report on the aggregate rate-overpotential profile with no information about the relative contributions from charge transfer and chemical steps. For the hydrogen evolution reaction (HER), the applied overpotential can be partitioned into a charge transfer overpotential, the overpotential necessary to drive proton-coupled electron transfer (PCET) to and from the surface, and a chemical overpotential, corresponding to a change in surface H activity. Reaction conditions can affect either or both the charge transfer and chemical components. Herein, we employ a Pd membrane double cell to spatially separate the charge transfer and chemical reactions steps of HER catalysis, enabling quantification of the chemical and charge transfer overpotential. We further analyze how each depend on pH, and the introduction of HER poisons and promoters. We find that for a given rate of H
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release, the chemical overpotential is constant across diverse reaction environments whereas the charge transfer overpotential is strongly sensitive to reaction conditions. These findings suggest that reaction condition dependent-HER efficiencies are driven predominantly by changes to the kinetics of charge transfer rather than the chemical reactivity of surface H.