A common role for astrocytes in rhythmic behaviours?

Authors acknowledge the Motor Neurone Disease (MND) Association UK (Miles/Apr18/863-791) and the Biotechnology and Biological Sciences Research Council (BBSRC; BB/M021793/1) for their funding and support.Astrocytes are a functionally diverse form of glial cell involved in various aspects of nervous system infrastructure, from the metabolic and structural support of neurons to direct neuromodulation of synaptic activity. Investigating how astrocytes behave in functionally related circuits may help us understand whether there is any conserved logic to the role of astrocytes within neuronal networks. Astrocytes are implicated as key neuromodulatory cells within neural circuits that control a number of rhythmic behaviours such as breathing, locomotion and circadian sleep-wake cycles. In this review, we examine the evidence that astrocytes are directly involved in the regulation of the neural circuits underlying six different rhythmic behaviours: locomotion, breathing, chewing, gastrointestinal motility, circadian sleep-wake cycles and oscillatory feeding behaviour. We discuss how astrocytes are integrated into the neuronal networks that regulate these behaviours, and identify the potential gliotransmission signalling mechanisms involved. From reviewing the evidence of astrocytic involvement in a range of rhythmic behaviours, we reveal a heterogenous array of gliotransmission mechanisms, which help to regulate neuronal networks. However, we also observe an intriguing thread of commonality, in the form of purinergic gliotransmission, which is frequently utilised to facilitate feedback inhibition within rhythmic networks to constrain a given behaviour within its operational range.PostprintPeer reviewe

Adaptive foveated single-pixel imaging with dynamic super-sampling

As an alternative to conventional multi-pixel cameras, single-pixel cameras enable images to be recorded using a single detector that measures the correlations between the scene and a set of patterns. However, to fully sample a scene in this way requires at least the same number of correlation measurements as there are pixels in the reconstructed image. Therefore single-pixel imaging systems typically exhibit low frame-rates. To mitigate this, a range of compressive sensing techniques have been developed which rely on a priori knowledge of the scene to reconstruct images from an under-sampled set of measurements. In this work we take a different approach and adopt a strategy inspired by the foveated vision systems found in the animal kingdom - a framework that exploits the spatio-temporal redundancy present in many dynamic scenes. In our single-pixel imaging system a high-resolution foveal region follows motion within the scene, but unlike a simple zoom, every frame delivers new spatial information from across the entire field-of-view. Using this approach we demonstrate a four-fold reduction in the time taken to record the detail of rapidly evolving features, whilst simultaneously accumulating detail of more slowly evolving regions over several consecutive frames. This tiered super-sampling technique enables the reconstruction of video streams in which both the resolution and the effective exposure-time spatially vary and adapt dynamically in response to the evolution of the scene. The methods described here can complement existing compressive sensing approaches and may be applied to enhance a variety of computational imagers that rely on sequential correlation measurements.Comment: 13 pages, 5 figure

M-type potassium currents differentially affect activation of motoneuron subtypes and tune recruitment gain

Funding: Royal Society: NIF/R1/180091; Wellcome Trust: 204821/Z/16/Z; Canadian Institute for Health Research: 202012MFE – 459188 – 297534.The size principle is a key mechanism governing the orderly recruitment of motor units and is believed to be dependent on passive properties of the constituent motoneurons. However, motoneurons are endowed with voltage-sensitive ion channels that create non-linearities in their input-output functions. Here we describe a role for the M-type potassium current, conducted by KCNQ channels, in the control of motoneuron recruitment in mice. Motoneurons were studied with whole-cell patch clamp electrophysiology in transverse spinal slices and identified based on delayed (fast) and immediate (slow) onsets of repetitive firing. M-currents were larger in delayed compared to immediate firing motoneurons, which was not reflected by variations in the presence of Kv7.2 or Kv7.3 subunits. Instead, a more depolarized spike threshold in delayed-firing motoneurons afforded a greater proportion of the total M-current to become activated within the subthreshold voltage range, which translated to a greater influence on their recruitment with little influence on their firing rates. Pharmacological activation of M-currents also influenced motoneuron recruitment at the population level, producing a rightward shift in the recruitment curve of monosynaptic reflexes within isolated mouse spinal cords. These results demonstrate a prominent role for M-type potassium currents in regulating the function of motor units, which occurs primarily through the differential control of motoneuron subtype recruitment. More generally, these findings highlight the importance of active properties mediated by voltage-sensitive ion channels in the differential control of motoneuron recruitment, which is a key mechanism for the gradation of muscle force.Publisher PDFPeer reviewe

Detection limits of organic compounds achievable with intense, short-pulse lasers

Many organic molecules have strong absorption bands which can be accessed by ultraviolet short pulse lasers to produce efficient ionization. This resonant multiphoton ionization scheme has already been exploited as an ionization source in time-of-flight mass spectrometers used for environmental trace analysis. In the present work we quantify the ultimate potential of this technique by measuring absolute ion yields produced from the interaction of 267 nm femtosecond laser pulses with the organic molecules indole and toluene, and gases Xe, N2 and O2. Using multiphoton ionization cross sections extracted from these results, we show that the laser pulse parameters required for real-time detection of aromatic molecules at concentrations of one part per trillion in air and a limit of detection of a few attomoles are achievable with presently available commercial laser systems. The potential applications for the analysis of human breath, blood and tissue samples are discussed

Analisis Data Kualitatif: Buku Sumber Tentang Metode-metode Baru

Penelitian dengan data kualitatif • Kebutuhan apakah yang dirasakan paling mendesak oleh para peneliti dalam bidang-bidang ilmu tentang manusia? • Bagaimana kita dapat menggambarkan makna yang sahih dari data kualitatif? • Metode analisis apakah yang dapat kita gunakan: yang praktis, dapat diterima, dan tidak menyesatkan? Semua jawaban dari pertanyaan-pertanyaan itu memang dibutuhkan oleh para peneliti, dan jawabanya harus dapat dipertanggung jawabkan secara ilmiah. Bagi para peneliti, data kualitatif memang merupakan sumber dari deskripsi yang luas, kokoh landasanya, dan pasti memuat penjelasannya, dan pasti memuat penjelasan tentang semua proses yang terjadi dalam lingkupan setempat. Karena itu alur pristiwa dapat diikuti dan dipahami. Data-data kualitatif para peneliti dapat memperoleh temuan-temuan yang tidak terduga. Buku ini dapat digunakan secara praktis, karena disusun dengan sistematis, disertai contoh-contoh yang komunikatif. Buku ini penting bagi para peneliti, sarjana dan mahasiswa, yang ingin memperoleh kesimnpulan-kesimpulan yang tidak samar-samar dan meragukan, tetapi yang beralasan kuat serta sahih

Street View Data Collection Design for Disaster Reconnaissance

Over the last decade, street-view type images have been used across disciplines to generate and understand various place-based metrics. However efforts to collect this data were often meant to support investigator-driven research without regard to the utility of the data for other researchers. To address this, we describe our methods for collecting and publishing longitudinal data of this type in the wake of the COVID-19 pandemic and discuss some of the challenges we encountered along the way. Our process included designing a route taking into account both broad area canvassing and community capitals transects. We also implemented procedures for uploading and publishing data from each survey. Our methods successfully generated the kind of longitudinal data that can be beneficial to a variety of research disciplines. However, there were some challenges with data collection consistency and the sheer magnitude of data produced. Overall, our approach demonstrates the feasibility of generating longitudinal street-view data in the wake of a disaster event. Based on our experience, we provide recommendations for future researchers attempting to create a similar data set.Comment: 11 pages, 2 figures, 1 tabl

Modulation of spinal motor networks by astrocyte-derived adenosine is dependent on D1-like dopamine receptor signalling

D.A. was supported by funds from a Wellcome Trust Institutional Strategic Support Fund grant. G.B.M. and M.J.B. received support from Biotechnology and Biological Science Research Grant BB/M021793/1.Astrocytes modulate many neuronal networks, including spinal networks responsible for the generation of locomotor behavior. Astrocytic modulation of spinal motor circuits involves release of ATP from astrocytes, hydrolysis of ATP to adenosine, and subsequent activation of neuronal A1 adenosine receptors (A1Rs). The net effect of this pathway is a reduction in the frequency of locomotor-related activity. Recently, it was proposed that A1Rs modulate burst frequency by blocking the D1-like dopamine receptor (D1LR) signaling pathway; however, adenosine also modulates ventral horn circuits by dopamine-independent pathways. Here, we demonstrate that adenosine produced upon astrocytic stimulation modulates locomotor-related activity by counteracting the excitatory effects of D1LR signaling and does not act by previously described dopamine-independent pathways. In spinal cord preparations from postnatal mice, a D1LR agonist, SKF 38393, increased the frequency of locomotor-related bursting induced by 5-hydroxytryptamine and N-methyl-d-aspartate. Bath-applied adenosine reduced burst frequency only in the presence of SKF 38393, as did adenosine produced after activation of protease-activated receptor-1 to stimulate astrocytes. Furthermore, the A1R antagonist 8-cyclopentyl-1,3-dipropylxanthine enhanced burst frequency only in the presence of SKF 38393, indicating that endogenous adenosine produced by astrocytes during network activity also acts by modulating D1LR signaling. Finally, modulation of bursting by adenosine released upon stimulation of astrocytes was blocked by protein kinase inhibitor-(14–22) amide, a protein kinase A (PKA) inhibitor, consistent with A1R-mediated antagonism of the D1LR/adenylyl cyclase/PKA pathway. Together, these findings support a novel, astrocytic mechanism of metamodulation within the mammalian spinal cord, highlighting the complexity of the molecular interactions that specify motor output.Publisher PDFPeer reviewe

Synaptic expression of TAR-DNA-binding protein 43 in the mouse spinal cord determined using super-resolution microscopy

Funding: This work was supported by Motor Neurone Disease (MND) Association UK (Miles/Apr18/863-791), Chief Scientist Office, RS Macdonald Charitable Trust, ALS CURE Project, the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (695568 SYNNOVATE), Simons Foundation Autism Research Initiative (529085), and the Wellcome Trust (Technology Development grant 202932).Amyotrophic Lateral Sclerosis (ALS) is characterised by a loss of motor neurons in the brain and spinal cord that is preceded by early-stage changes in synapses that may be associated with TAR-DNA-Binding Protein 43 (TDP-43) pathology. Cellular inclusions of hyperphosphorylated TDP-43 (pTDP-43) are a key hallmark of neurodegenerative diseases such ALS. However, there has been little characterisation of the synaptic expression of TDP-43 inside subpopulations of spinal cord synapses. This study utilises a range of high-resolution and super-resolution microscopy techniques with immunolabelling, as well as an aptamer-based TDP-43 labelling strategy visualised with single-molecule localisation microscopy, to characterise and quantify the presence of pTDP-43 in populations of excitatory synapses near where motor neurons reside in the lateral ventral horn of the mouse lumbar spinal cord. We observe that TDP-43 is expressed in approximately half of spinal cord synapses as nanoscale clusters. Synaptic TDP-43 clusters are found most abundantly at synapses associated with VGLUT1-positive presynaptic terminals, compared to VGLUT2-associated synapses. Our nanoscopy techniques showed no difference in the subsynaptic expression of pTDP-43 in the ALS mouse model, SOD1G93a, compared to healthy controls, despite prominent structural deficits in VGLUT1-associated synapses in SOD1G93a mice. This research characterizes the basic synaptic expression of TDP-43 with nanoscale precision and provides a framework with which to investigate the potential relationship between TDP-43 pathology and synaptic pathology in neurodegenerative diseases.Publisher PDFPeer reviewe

A meta-regression of the impact of policy on the efficacy of individual placement and support

Objective: Individual placement and support (IPS) has shown consistently better outcomes on competitive employment for patients with severe mental illness than traditional vocational rehabilitation. The evidence for efficacy originates from few countries, and generalization to different countries has been questioned. This has delayed implementation of IPS and led to requests for country-specific RCTs. This meta-analysis examines if evidence for IPS efficacy can be generalized between rather different countries. Methods: A systematic search was conducted according to PRISMA guidelines to identify RCTs. Overall efficacy was established by meta-analysis. The generalizability of IPS efficacy between countries was analysed by random-effects meta-regression, employing country- and date-specific contextual data obtained from the OECD and the World Bank. Results: The systematic review identified 27 RCTs. Employment rates are more than doubled in IPS compared with standard vocational rehabilitation (RR 2.07 95% CI 1.82–2.35). The efficacy of IPS was marginally moderated by strong legal protection against dismissals. It was not moderated by regulation of temporary employment, generosity of disability benefits, type of integration policies, GDP, unemployment rate or employment rate for those with low education. Conclusions: The evidence for efficacy of IPS is very strong. The efficacy of IPS can be generalized between countries