Three-dimensional reconstruction of synapses and dendritic spines in the rat and ground squirrel hippocampus: New structural-functional paradigms for synaptic function

Published data are reviewed along with our own data on synaptic plasticity and rearrangements of synaptic organelles in the central nervous system. Contemporary laser scanning and confocal microscopy techniques are discussed, along with the use of serial ultrathin sections for in vivo and in vitro studies of dendritic spines, including those addressing relationships between morphological changes and the efficiency of synaptic transmission, especially in conditions of the long-term potentiation model. Different categories of dendritic spines and postsynaptic densities are analyzed, as are the roles of filopodia in originating spines. The role of serial ultrathin sections for unbiased quantitative stereological analysis and three-dimensional reconstruction is assessed. The authors data on the formation of more than two synapses on single mushroom spines on neurons in hippocampal field CA1 are discussed. Analysis of these data provides evidence for new paradigms in both the organization and functioning of synapses

A multilevel neo-institutional analysis of infection prevention and control in English hospitals: coerced safety culture change?

Despite committed policy, regulative and professional efforts on healthcare safety, little is known about how such macro-interventions permeate organisations and shape culture over time. Informed by neo-institutional theory, we examined how inter-organisational influences shaped safety practices and inter-subjective meanings following efforts for coerced culture change. We traced macro-influences from 2000 to 2015 in infection prevention and control (IPC). Safety perceptions and meanings were inductively analysed from 130 in-depth qualitative interviews with senior- and middle-level managers from 30 English hospitals. A total of 869 institutional interventions were identified; 69% had a regulative component. In this context of forced implementation of safety practices, staff experienced inherent tensions concerning the scope of safety, their ability to be open and prioritisation of external mandates over local need. These tensions stemmed from conflicts among three co-existing institutional logics prevalent in the NHS. In response to requests for change, staff flexibly drew from a repertoire of cognitive, material and symbolic resources within and outside their organisations. They crafted 'strategies of action', guided by a situated assessment of first-hand practice experiences complementing collective evaluations of interventions such as 'pragmatic', 'sensible' and also 'legitimate'. Macro-institutional forces exerted influence either directly on individuals or indirectly by enriching the organisational cultural repertoire

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Patient safety culture in care homes for older people: a scoping review

Background: In recent years, there has been an increasing focus on the role of safety culture in preventing incidents such as medication errors and falls. However, research and developments in safety culture has predominantly taken place in hospital settings, with relatively less attention given to establishing a safety culture in care homes. Despite safety culture being accepted as an important quality indicator across all health and social care settings, the understanding of culture within social care settings remains far less developed than within hospitals. It is therefore important that the existing evidence base is gathered and reviewed in order to understand safety culture in care homes. Methods: A scoping review was undertaken to describe the availability of evidence related to care homes’ patient safety culture, what these studies focused on, and identify any knowledge gaps within the existing literature. Included papers were each reviewed by two authors for eligibility and to draw out information relevant to the scoping review. Results: Twenty-four empirical papers and one literature review were included within the scoping review. The collective evidence demonstrated that safety culture research is largely based in the USA, within Nursing Homes rather than Residential Home settings. Moreover, the scoping review revealed that empirical evidence has predominantly used quantitative measures, and therefore the deeper levels of culture have not been captured in the evidence base. Conclusions: Safety culture in care homes is a topic that has not been extensively researched. The review highlights a number of key gaps in the evidence base, which future research into safety culture in care home should attempt to address

Calmodulin Activation by Calcium Transients in the Postsynaptic Density of Dendritic Spines

The entry of calcium into dendritic spines can trigger a sequence of biochemical reactions that begins with the activation of calmodulin (CaM) and ends with long-term changes to synaptic strengths. The degree of activation of CaM can depend on highly local elevations in the concentration of calcium and the duration of transient increases in calcium concentration. Accurate measurement of these local changes in calcium is difficult because the spaces are so small and the numbers of molecules are so low. We have therefore developed a Monte Carlo model of intracellular calcium dynamics within the spine that included calcium binding proteins, calcium transporters and ion channels activated by voltage and glutamate binding. The model reproduced optical recordings using calcium indicator dyes and showed that without the dye the free intracellular calcium concentration transient was much higher than predicted from the fluorescent signal. Excitatory postsynaptic potentials induced large, long-lasting calcium gradients across the postsynaptic density, which activated CaM. When glutamate was released at the synapse 10 ms before an action potential occurred, simulating activity patterns that strengthen hippocampal synapses, the calcium gradient and activation of CaM in the postsynaptic density were much greater than when the order was reversed, a condition that decreases synaptic strengths, suggesting a possible mechanism underlying the induction of long-term changes in synaptic strength. The spatial and temporal mechanisms for selectivity in CaM activation demonstrated here could be used in other signaling pathways

Fragile X Related Protein 1 Clusters with Ribosomes and Messenger RNAs at a Subset of Dendritic Spines in the Mouse Hippocampus

The formation and storage of memories in neuronal networks relies on new protein synthesis, which can occur locally at synapses using translational machinery present in dendrites and at spines. These new proteins support long-lasting changes in synapse strength and size in response to high levels of synaptic activity. To ensure that proteins are made at the appropriate time and location to enable these synaptic changes, messenger RNA (mRNA) translation is tightly controlled by dendritic RNA-binding proteins. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein with high homology to Fragile X Mental Retardation Protein (FMRP) and is known to repress and activate mRNA translation in non-neuronal cells. However, unlike FMRP, very little is known about the role of FXR1P in the central nervous system. To understand if FXR1P is positioned to regulate local mRNA translation in dendrites and at synapses, we investigated the expression and targeting of FXR1P in developing hippocampal neurons in vivo and in vitro. We found that FXR1P was highly expressed during hippocampal development and co-localized with ribosomes and mRNAs in the dendrite and at a subset of spines in mouse hippocampal neurons. Our data indicate that FXR1P is properly positioned to control local protein synthesis in the dendrite and at synapses in the central nervous system

A Daily Diary Approach to the Examination of Chronic Stress, Daily Hassles and Safety Perceptions in Hospital Nursing

Purpose: Stress is a significant concern for individuals and organisations. Few studies have explored stress, burnout and patient safety in hospital nursing on a daily basis at the individual level. This study aimed to examine the effects of chronic stress and daily hassles on safety perceptions, the effect of chronic stress on daily hassles experienced and chronic stress as a potential moderator. Method: Utilising a daily diary design, 83 UK hospital nurses completed three end-of-shift diaries, yielding 324 person days. Hassles, safety perceptions and workplace cognitive failure were measured daily, and a baseline questionnaire included a measure of chronic stress. Hierarchical multivariate linear modelling was used to analyse the data. Results: Higher chronic stress was associated with more daily hassles, poorer perceptions of safety and being less able to practise safely, but not more workplace cognitive failure. Reporting more daily hassles was associated with poorer perceptions of safety, being less able to practise safely and more workplace cognitive failure. Chronic stress did not moderate daily associations. The hassles reported illustrate the wide-ranging hassles nurses experienced. Conclusion: The findings demonstrate, in addition to chronic stress, the importance of daily hassles for nurses’ perceptions of safety and the hassles experienced by hospital nurses on a daily basis. Nurses perceive chronic stress and daily hassles to contribute to their perceptions of safety. Measuring the number of daily hassles experienced could proactively highlight when patient safety threats may arise, and as a result, interventions could usefully focus on the management of daily hassles

Quantal variability at glutamatergic synapses in area CA1 of the rat neonatal hippocampus

Quantal variability was determined at glutamatergic synapses in the neonatal (postnatal days 1-7) rat hippocampal slice preparation. Synaptic AMPA and NMDA quantal EPSCs were recorded from CA1 pyramidal neurones using the whole-cell, or perforated, patch-clamp technique.Release was evoked by minimal stimulation using brief trains (10 impulses, 50 Hz), and various tests ascertained that this stimulation activated single release sites releasing single vesicles.Both AMPA and NMDA quantal responses at a given release site varied considerably in magnitude, the coefficient of variation (CV) among the synapses averaging 0.39 and 0.30, respectively. This variability differed among the synapses, from 0.2 to 0.7, and 0.10 to 0.50, respectively, and CV values of AMPA responses co-varied with those of the NMDA responses.Both for AMPA and NMDA, low CV values were associated with a Gaussian distribution of EPSC peak values, whereas synapses with high CV values displayed distributions skewed towards lower values.Analysis of successive NMDA responses during a train revealed a considerable degree of non-saturation of NMDA receptors by a single vesicle.The results are compatible with a quantal variability based, to a large extent, on non-saturated AMPA and NMDA responses fluctuating as a function of the amount of transmitter released from each vesicle