Hippocampal network oscillations - recent insights from in vitro experiments.

Network oscillations are present throughout the mammalian brain. They are important for certain cognitive functions, such as learning and memory. The hippocampus exhibits prominent oscillations similar to those seen in other parts of the cortex. Due to its highly organised lamellar structure, ex vivo and in vitro preparations from the hippocampus have provided experimental models within which to study network oscillations. As such, experiments in hippocampal slices continue to progress our understanding about both the mechanisms and functions of cortical network oscillations. Here, advances from the past two years are summarised, and the current state of the field discussed.The authors are grateful for research funding from the BBSRC, UK. JLB is supported by a CASE studentship from the BBSRC.This is the final published version. It is also available from Elsevier at http://www.sciencedirect.com/science/article/pii/S0959438814001627#

The Hippocampal Cacophony: Multiple Layers of Communication

Locally generated gamma oscillations synchronize spikes, but the nature of coupling between regions remains unclear. In this issue of Neuron, Schomburg et al. (2014) show that afferent gamma input fails to entrain hippocampal output, suggesting limited propagation of gamma waves

Role of angiopoietin-like protein 3 in sugar-induced dyslipidemia in rhesus macaques: suppression by fish oil or RNAi.

Angiopoietin-like protein 3 (ANGPTL3) inhibits lipid clearance and is a promising target for managing cardiovascular disease. Here we investigated the effects of a high-sugar (high-fructose) diet on circulating ANGPTL3 concentrations in rhesus macaques. Plasma ANGPTL3 concentrations increased ∼30% to 40% after 1 and 3 months of a high-fructose diet (both P < 0.001 vs. baseline). During fructose-induced metabolic dysregulation, plasma ANGPTL3 concentrations were positively correlated with circulating indices of insulin resistance [assessed with fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR)], hypertriglyceridemia, adiposity (assessed as leptin), and systemic inflammation [C-reactive peptide (CRP)] and negatively correlated with plasma levels of the insulin-sensitizing hormone adropin. Multiple regression analyses identified a strong association between circulating APOC3 and ANGPTL3 concentrations. Higher baseline plasma levels of both ANGPTL3 and APOC3 were associated with an increased risk for fructose-induced insulin resistance. Fish oil previously shown to prevent insulin resistance and hypertriglyceridemia in this model prevented increases of ANGPTL3 without affecting systemic inflammation (increased plasma CRP and interleukin-6 concentrations). ANGPTL3 RNAi lowered plasma concentrations of ANGPTL3, triglycerides (TGs), VLDL-C, APOC3, and APOE. These decreases were consistent with a reduced risk of atherosclerosis. In summary, dietary sugar-induced increases of circulating ANGPTL3 concentrations after metabolic dysregulation correlated positively with leptin levels, HOMA-IR, and dyslipidemia. Targeting ANGPTL3 expression with RNAi inhibited dyslipidemia by lowering plasma TGs, VLDL-C, APOC3, and APOE levels in rhesus macaques

Surface control system for the 15 meter hoop-column antenna

The 15-meter hoop-column antenna fabricated by the Harris Corporation under contract to the NASA Langley Research Center is described. The antenna is a deployable and restowable structure consisting of a central telescoping column, a 15-meter-diameter folding hoop, and a mesh reflector surface. The hoop is supported and positioned by 48 quartz cords attached to the column above the hoop, and by 24 graphite cords from the base of the antenna column. The RF reflective surface is a gold plated molybdenum wire mesh supported on a graphite cord truss structure which is attached between the hoop and the column. The surface contour is controlled by 96 graphite cords from the antenna base to the rear of the truss assembly. The antenna is actually a quadaperture reflector with each quadrant of the surface mesh shaped to produce an offset parabolic reflector. Results of near-field and structural tests are given. Controls structures and electromagnetics interaction, surface control system requirements, mesh control adjustment, surface control system actuator assembly, surface control system electronics, the system interface unit, and control stations are discussed

Effects of canagliflozin on cardiovascular biomarkers in older adults with type 2 diabetes

Background: Sodium glucose co-transporter 2 (SGLT2) inhibitors may reduce cardiovascular and heart failure risk in patients with type 2 diabetes mellitus (T2DM). Objectives: To examine the effects of canagliflozin on cardiovascular biomarkers in older patients with T2DM. Methods: In 666 T2DM patients randomized to receive canagliflozin 100 or 300 mg or placebo, we assessed median percent change in serum N-terminal pro-B type natriuretic peptide (NT-proBNP), high-sensitivity troponin I (hsTnI) , soluble (s)ST2, and galectin-3 from baseline to 26, 52, and 104 weeks. Results: Both serum NT-proBNP and serum hsTnI levels increased in placebo recipients but remained largely unchanged in those randomized to canagliflozin. Hodges-Lehmann estimates of the difference in median percent change between pooled canagliflozin and placebo were –15.0%, –16.1%, and –26.8% for NT-proBNP, and –8.3%, –11.9%, and –10.0% for hsTnI at weeks 26, 52, and 104, respectively (all P <0.05). Serum sST2 was unchanged with canagliflozin and placebo over 104 weeks. Serum galectin-3 modestly increased from baseline with canagliflozin versus placebo, with significant differences observed at 26 and 52 weeks but not at 104 weeks. These results remained unchanged when only patients with complete samples were assessed. Conclusions: Compared to placebo, treatment with canagliflozin delayed rise in serum NT-proBNP and hsTnI over 2 years in older T2DM patients. These cardiac biomarker data provide support for beneficial cardiovascular effect of SGLT2 inhibitors in T2DM

Comparison of three gamma oscillations in the mouse entorhinal-hippocampal system.

The entorhinal-hippocampal system is an important circuit in the brain, essential for certain cognitive tasks such as memory and navigation. Different gamma oscillations occur in this circuit, with the medial entorhinal cortex (mEC), CA3 and CA1 all generating gamma oscillations with different properties. These three gamma oscillations converge within CA1, where much work has gone into trying to isolate them from each other. Here, we compared the gamma generators in the mEC, CA3 and CA1 using optogenetically induced theta-gamma oscillations. Expressing channelrhodopsin-2 in principal neurons in each of the three regions allowed for the induction of gamma oscillations via sinusoidal blue light stimulation at theta frequency. Recording the oscillations in CA1 in vivo, we found that CA3 stimulation induced slower gamma oscillations than CA1 stimulation, matching in vivo reports of spontaneous CA3 and CA1 gamma oscillations. In brain slices ex vivo, optogenetic stimulation of CA3 induced slower gamma oscillations than stimulation of either mEC or CA1, whose gamma oscillations were of similar frequency. All three gamma oscillations had a current sink-source pair between the perisomatic and dendritic layers of the same region. Taking advantage of this model to analyse gamma frequency mechanisms in slice, we showed using pharmacology that all three gamma oscillations were dependent on the same types of synaptic receptor, being abolished by blockade of either type A γ-aminobutyric acid receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors, and insensitive to blockade of N-methyl-d-aspartate receptors. These results indicate that a fast excitatory-inhibitory feedback loop underlies the generation of gamma oscillations in all three regions

High level design proof of a reliable computing platform

The main objectives are: to establish hardware/software platform for ultra-reliable computing; to use fault tolerant computer architecture; to use formal methods to prevent design and implementation errors; and to construct reliability model to quantify reliability estimate. The results show that: ultra-reliable control systems are hard to achieve; simple fault tolerant design is postulated; formal specification of design is constructed; and preliminary correctness proofs are obtained

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

Crossing the Brown Dwarf Desert Using Adaptive Optics: A Very Close L-Dwarf Companion to the Nearby Solar Analog HR 7672

We have found a very faint companion to the active solar analog HR 7672 (HD 190406; GJ 779; 15 Sge). Three epochs of high resolution imaging using adaptive optics (AO) at the Gemini-North and Keck II Telescopes demonstrate that HR 7672B is a common proper motion companion, with a separation of 0.79" (14 AU) and a 2.16 um flux ratio of 8.6 mags. Using follow-up K-band spectroscopy from Keck AO+NIRSPEC, we measure a spectral type of L4.5+/-1.5. This is the closest ultracool companion around a main sequence star found to date by direct imaging. We estimate the primary has an age of 1-3 Gyr. Assuming coevality, the companion is most likely substellar, with a mass of 55-78 Mjup based on theoretical models. The primary star shows a long-term radial velocity trend, and we combine the radial velocity data and AO imaging to set a firm (model-independent) lower limit of 48 Mjup. In contrast to the paucity of brown dwarf companions at <~4 AU around FGK dwarfs, HR 7672B implies that brown dwarf companions do exist at separations comparable to those of the giant planets in our own solar system. Its presence is at variance with scenarios where brown dwarfs form as ejected stellar embryos. Moreover, since HR 7672B is likely too massive to have formed in a circumstellar disk as planets are believed to, its discovery suggests that a diversity of physical processes act to populate the outer regions of exoplanetary systems.Comment: Astrophysical Journal, in pres

Large-area submillimeter resolution CdZnTe strip detector for astronomy

We report the first performance measurements of a sub-millimeter CdZnTe strip detector developed as a prototype for space-borne astronomical instruments. Strip detector arrays can be used to provide two-dimensional position resolution with fewer electronic channels than pixellated arrays. Arrays of this type and other candidate technologies are under investigation for the position-sensitive backplane detector for a coded-aperture telescope operating in the range of 30 - 300 keV. The prototype is a 1.4 mm thick, 64 multiplied by 64 stripe CdZnTe array of 0.375 mm pitch in both dimensions, approximately one square inch of sensitive area. Pulse height spectra in both single and orthogonal stripe coincidence mode were recorded at several energies. The results are compared to slab- and pixel-geometry detector spectra. The room-temperature energy resolution is less than 10 keV (FWHM) for 122 keV photons with a peak-to-valley ratio greater than 5:1. The response to photons with energies up to 662 keV appears to be considerably improved relative to that of previously reported slab and pixel detectors. We also show that strip detectors can yield spatial and energy resolutions similar to those of pixellated arrays with the same dimensions. Electrostatic effects on the pulse heights, read-out circuit complexity, and issues related to design of space borne instruments are also discussed