Intrinsic Cornu Ammonis Area 1 Theta-Nested Gamma Oscillations Induced by Optogenetic Theta Frequency Stimulation.

UNLABELLED: Gamma oscillations (30-120 Hz) are thought to be important for various cognitive functions, including perception and working memory, and disruption of these oscillations has been implicated in brain disorders, such as schizophrenia and Alzheimer's disease. The cornu ammonis area 1 (CA1) of the hippocampus receives gamma frequency inputs from upstream regions (cornu ammonis area 3 and medial entorhinal cortex) and generates itself a faster gamma oscillation. The exact nature and origin of the intrinsic CA1 gamma oscillation is still under debate. Here, we expressed channel rhodopsin-2 under the CaMKIIα promoter in mice and prepared hippocampal slices to produce a model of intrinsic CA1 gamma oscillations. Sinusoidal optical stimulation of CA1 at theta frequency was found to induce robust theta-nested gamma oscillations with a temporal and spatial profile similar to CA1 gamma in vivo The results suggest the presence of a single gamma rhythm generator with a frequency range of 65-75 Hz at 32 °C. Pharmacological analysis found that the oscillations depended on both AMPA and GABAA receptors. Cell-attached and whole-cell recordings revealed that excitatory neuron firing slightly preceded interneuron firing within each gamma cycle, suggesting that this intrinsic CA1 gamma oscillation is generated with a pyramidal-interneuron circuit mechanism. SIGNIFICANCE STATEMENT: This study demonstrates that the cornu ammonis area 1 (CA1) is capable of generating intrinsic gamma oscillations in response to theta input. This gamma generator is independent of activity in the upstream regions, highlighting that CA1 can produce its own gamma oscillation in addition to inheriting activity from the upstream regions. This supports the theory that gamma oscillations predominantly function to achieve local synchrony, and that a local gamma generated in each area conducts the signal to the downstream region.J.L.B. is support by a Biotechnology and Biological Sciences Research Council CASE Studentship in collaboration with Eli Lilly and Company, and P.R.F.M. is supported by a CAPES Science without Borders Cambridge Scholarship.This is the final version of the article. It first appeared from the Society for Neuroscience via http://dx.doi.org/10.1523/JNEUROSCI.3150-15.201

Grafting: “the boyz” just doing business? Deviant entrepreneurship in street gangs

Purpose: The purpose of this paper is to attempt to disseminate street gang research by Hesketh (2018) that has identified young people’s perceptions between employment and criminality in areas of Merseyside becoming blurred. In particular, disenfranchised young males are turning to involvement with drug dealing street gangs as a substitute for employment Design/methodology/approach: The research involved the use of a hybrid design using an adapted version of Wengraf’s (2001) biographic narrative interpretive method as the means for data collection with Strauss and Corbin’s (1995) grounded theory approach as the means of analysis Findings: Such is the demand for Class A drugs in night-time economies that street gangs in areas close to such economies are adding a dark business-like dimension for which Hesketh (2018) has termed “Deviant Entrepreneurship”. This can range from selling drugs on behalf of adult organised crime figures (known on the streets of Liverpool as “grafting”) to self-employment as sole trading deviant group enterprises having several “grafts” that recent research by Robinson, McLean and Densley (2018) has noted, has extended into the annals of Criminal Child Exploitation. Research limitations/implications: Data were derived from a sample of young males, thus, no observations can be made about females involved in gangs Practical implications: The research highlights the need for more gang interventions that focus on building opportunities within marginalised areas. It also suggests as Andell (2019) points out a need for a fresh approach to countering gang culture Social implications: The paper concludes by suggesting that Merseyside is only one in many marginalised areas of the UK facing a similar problem as young people involved in street gangs attempt to realise their potential not through legitimate employment means but through dark entrepreneurial techniques learnt from older peers and adult figures Originality/value: The findings are taken from a PhD thesis by Robert F. Hesketh University of Chester

Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin neurons.

KEY POINTS: Neurons in the hypothalamus of the brain which secrete the peptide kisspeptin are important regulators of reproduction, and normal reproductive development. Electrical activity, in the form of action potentials, or spikes, leads to secretion of peptides and neurotransmitters, influencing the activity of downstream neurons; in kisspeptin neurons, this activity is highly irregular, but the mechanism of this is not known. In this study, we show that irregularity depends on the presence of a particular type of potassium ion channel in the membrane, which opens transiently in response to electrical excitation. The results contribute to understanding how kisspeptin neurons generate and time their membrane potential spikes, and how reliable this process is. Improved understanding of the activity of kisspeptin neurons, and how it shapes their secretion of peptides, is expected to lead to better treatment for reproductive dysfunction and disorders of reproductive development. ABSTRACT: Kisspeptin neurons in the hypothalamus are critically involved in reproductive function, via their effect on GnRH neuron activity and consequent gonadotropin release. Kisspeptin neurons show an intrinsic irregularity of firing, but the mechanism of this remains unclear. To address this, we carried out targeted whole-cell patch-clamp recordings of kisspeptin neurons in the arcuate nucleus (Kiss1Arc ), in brain slices isolated from adult male Kiss-Cre:tdTomato mice. Cells fired irregularly in response to constant current stimuli, with a wide range of spike time variability, and prominent subthreshold voltage fluctuations. In voltage clamp, both a persistent sodium (NaP) current and a fast transient (A-type) potassium current were apparent, activating at potentials just below the threshold for spiking. These currents have also previously been described in irregular-spiking cortical interneurons, in which the A-type current, mediated by Kv4 channels, interacts with NaP current to generate complex dynamics of the membrane potential, and irregular firing. In Kiss1Arc neurons, A-type current was blocked by phrixotoxin, a specific blocker of Kv4.2/4.3 channels, and consistent expression of Kv4.2 transcripts was detected by single-cell RT-PCR. In addition, firing irregularity was correlated to the density of A-type current in the membrane. Using conductance injection, we demonstrated that adding Kv4-like potassium conductance (gKv4 ) to a cell produces a striking increase in firing irregularity, and excitability is reduced, while subtracting gKv4 has the opposite effects. Thus, we propose that Kv4 interacting dynamically with NaP is a key determinant of the irregular firing behaviour of Kiss1Arc neurons, shaping their physiological function in gonadotropin release

Simulating stable carbon isotopes in the ocean component of the FAMOUS general circulation model with MOSES1 (XOAVI)

Ocean circulation and the marine carbon cycle can be indirectly inferred from stable and radiogenic carbon isotope ratios (δ13C and Δ14C, respectively), measured directly in the water column, or recorded in geological archives such as sedimentary microfossils and corals. However, interpreting these records is non-trivial because they reflect a complex interplay between physical and biogeochemical processes. By directly simulating multiple isotopic tracer fields within numerical models, we can improve our understanding of the processes that control large-scale isotope distributions and interpolate the spatiotemporal gaps in both modern and palaeo datasets. We have added the stable isotope 13C to the ocean component of the FAMOUS coupled atmosphere–ocean general circulation model, which is a valuable tool for simulating complex feedbacks between different Earth system processes on decadal to multi-millennial timescales. We tested three different biological fractionation parameterisations to account for the uncertainty associated with equilibrium fractionation during photosynthesis and used sensitivity experiments to quantify the effects of fractionation during air–sea gas exchange and primary productivity on the simulated δ13CDIC distributions. Following a 10 000-year pre-industrial spin-up, we simulated the Suess effect (the isotopic imprint of anthropogenic fossil fuel burning) to assess the performance of the model in replicating modern observations. Our implementation captures the large-scale structure and range of δ13CDIC observations in the surface ocean, but the simulated values are too high at all depths, which we infer is due to biases in the biological pump. In the first instance, the new 13C tracer will therefore be useful for recalibrating both the physical and biogeochemical components of FAMOUS

Brain Rhythms Reveal a Hierarchical Network Organization

Recordings of ongoing neural activity with EEG and MEG exhibit oscillations of specific frequencies over a non-oscillatory background. The oscillations appear in the power spectrum as a collection of frequency bands that are evenly spaced on a logarithmic scale, thereby preventing mutual entrainment and cross-talk. Over the last few years, experimental, computational and theoretical studies have made substantial progress on our understanding of the biophysical mechanisms underlying the generation of network oscillations and their interactions, with emphasis on the role of neuronal synchronization. In this paper we ask a very different question. Rather than investigating how brain rhythms emerge, or whether they are necessary for neural function, we focus on what they tell us about functional brain connectivity. We hypothesized that if we were able to construct abstract networks, or “virtual brains”, whose dynamics were similar to EEG/MEG recordings, those networks would share structural features among themselves, and also with real brains. Applying mathematical techniques for inverse problems, we have reverse-engineered network architectures that generate characteristic dynamics of actual brains, including spindles and sharp waves, which appear in the power spectrum as frequency bands superimposed on a non-oscillatory background dominated by low frequencies. We show that all reconstructed networks display similar topological features (e.g. structural motifs) and dynamics. We have also reverse-engineered putative diseased brains (epileptic and schizophrenic), in which the oscillatory activity is altered in different ways, as reported in clinical studies. These reconstructed networks show consistent alterations of functional connectivity and dynamics. In particular, we show that the complexity of the network, quantified as proposed by Tononi, Sporns and Edelman, is a good indicator of brain fitness, since virtual brains modeling diseased states display lower complexity than virtual brains modeling normal neural function. We finally discuss the implications of our results for the neurobiology of health and disease

Stable endocytic structures navigate the complex pellicle of apicomplexan parasites

Apicomplexan parasites have immense impacts on humanity, but their basic cellular processes are often poorly understood. Where endocytosis occurs in these cells, how conserved this process is with other eukaryotes, and what the functions of endocytosis are across this phylum are major unanswered questions. Using the apicomplexan model Toxoplasma, we identified the molecular composition and behavior of unusual, fixed endocytic structures. Here, stable complexes of endocytic proteins differ markedly from the dynamic assembly/disassembly of these machineries in other eukaryotes. We identify that these endocytic structures correspond to the ‘micropore’ that has been observed throughout the Apicomplexa. Moreover, conserved molecular adaptation of this structure is seen in apicomplexans including the kelch-domain protein K13 that is central to malarial drug-resistance. We determine that a dominant function of endocytosis in Toxoplasma is plasma membrane homeostasis, rather than parasite nutrition, and that these specialized endocytic structures originated early in infrakingdom Alveolata likely in response to the complex cell pellicle that defines this medically and ecologically important ancient eukaryotic lineage

Multi-Dimensional Characterization of Battery Materials

Demand for low carbon energy storage has highlighted the importance of imaging techniques for the characterization of electrode microstructures to determine key parameters associated with battery manufacture, operation, degradation, and failure both for next generation lithium and other novel battery systems. Here, recent progress and literature highlights from magnetic resonance, neutron, X-ray, focused ion beam, scanning and transmission electron microscopy are summarized. Two major trends are identified: First, the use of multi-modal microscopy in a correlative fashion, providing contrast modes spanning length- and time-scales, and second, the application of machine learning to guide data collection and analysis, recognizing the role of these tools in evaluating large data streams from increasingly sophisticated imaging experiments

Multiple shifts and fractional integration in the us and uk unemployment rates

This paper analyses the long-run behaviour of the US and UK unemployment rates by testing for possibly fractional orders of integration and multiple shifts using a sample of over 100 annual observations. The results show that the orders of integration are higher than 0 in both series, which implies long memory. If we assume that the underlying disturbances are white noise, the values are higher than 0.5, i.e., nonstationary. However, if the disturbances are autocorrelated, the orders of integration are in the interval (0, 0.5), implying stationarity and mean-reverting behaviour. Moreover, when multiple shifts are taken into account, unemployment is more persistent in the US than in the UK, implying the need for stronger policy action in the former to bring unemployment back to its original level