Consequences of human Tau aggregation in the hippocampal formation of ageing mice in vivo

Intracellular aggregation of hyperphosphorylated Tau (pTau) in the brain is associated with cognitive and motor impairments, and ultimately neurodegeneration. We investigate how human pTau affects cells and network activity in the hippocampal formation of THY-Tau22 tauopathy model mice in vivo. We find that pTau preferentially accumulates in deep-layer pyramidal neurons, leading to neurodegeneration, and we establish that pTau spreads to oligodendrocytes. During goal-directed virtual navigation in aged transgenic mice, we detect fewer high-firing pyramidal cells, with the remaining cells retaining their coupling to theta oscillations. Analysis of network oscillations and firing patterns of pyramidal and GABAergic neurons recorded in head-fixed and freely-moving mice suggests preserved neuronal coordination. In spatial memory tests, transgenic mice have reduced short-term familiarity but spatial working and reference memory are surprisingly normal. We hypothesize that unimpaired subcortical network mechanisms implementing cortical neuronal coordination compensate for the widespread pTau aggregation, loss of high-firing cells and neurodegeneration.

Influence of Mong Duong fly ash on the physical properties of dry pressed ceramic tiles

Although fly ash is a solid waste of coal-fired power plants, it is also a potential raw material for the building materials industry. In the present work, the fly ash collected from Mong Duong I power plant was characterized and used as a substitute for kaolin and feldspar at sixteen percent of a ceramic tile raw mix. The results show that fly ash promotes sintering and helps upgrade wall tiles from unsatisfactory to grade BIIa and floor tiles from grade BIII to grade BIb. These changes have significant economic and environmental implications. However, due to a relatively high firing shrinkage, it is necessary to have appropriate adjustments if applied in industrial production.

Multiscale dynamics underlying neocortical slow oscillations

Slow oscillations in the sleeping and anesthetized brain invariantly emerge as an alternation between Up (high firing) and Down (almost quiescent) states. In cortex, they occur simultaneously in cell assemblies in different layers and propagate as traveling waves, a concerted activity at multiple scales whose interplay and role is still under debate. Slow oscillations have been reported to start in deep layers, more specifically in layer 5. Here, we studied the laminar organization of slow oscillations in the anesthetized rat cortex and we found that the activity leading to Up states actually initiates in layer 6, then spreads towards upper layers. Layer 5 cell assemblies have a threshold-like activation that can persist after layer 6 inactivation, giving rise to hysteresis loops like in "flip-flop" computational units. We found that such hysteresis is finely tuned by the columnar circuitry depending on the recent history of the local ongoing activity. Furthermore, thalamic inactivation reduced infragranular excitability without affecting the columnar activation pattern. We propose a role for layer 6 acting as a hub unraveling a hierarchy of cortical loops.

Compromised N-Glycosylation Processing of Kv3.1b Correlates with Perturbed Motor Neuron Structure and Locomotor Activity

Neurological difficulties commonly accompany individuals suffering from congenital disorders of glycosylation, resulting from defects in the N-glycosylation pathway. Vacant N-glycosylation sites (N220 and N229) of Kv3, voltage-gated K+ channels of high-firing neurons, deeply perturb channel activity in neuroblastoma (NB) cells. Here we examined neuron development, localization, and activity of Kv3 channels in wildtype AB zebrafish and CRISPR/Cas9 engineered NB cells, due to perturbations in N-glycosylation processing of Kv3.1b. We showed that caudal primary (CaP) motor neurons of zebrafish spinal cord transiently expressing fully glycosylated (WT) Kv3.1b have stereotypical morphology, while CaP neurons expressing partially glycosylated (N220Q) Kv3.1b showed severe maldevelopment with incomplete axonal branching and extension around the ventral musculature. Consequently, larvae expressing N220Q in CaP neurons had impaired swimming locomotor activity. We showed that replacement of complex N-glycans with oligomannose attached to Kv3.1b and at cell surface lessened Kv3.1b dispersal to outgrowths by altering the number, size, and density of Kv3.1b-containing particles in membranes of rat neuroblastoma cells. Opening and closing rates were slowed in Kv3 channels containing Kv3.1b with oligomannose, instead of complex N-glycans, which suggested a reduction in the intrinsic dynamics of the Kv3.1b α-subunit. Thus, N-glycosylation processing of Kv3.1b regulates neuronal development and excitability, thereby controlling motor activity.

Attractor cortical neurodynamics, schizophrenia, and depression

The local recurrent collateral connections between cortical neurons provide a basis for attractor neural networks for memory, attention, decision-making, and thereby for many aspects of human behavior. In schizophrenia, a reduction of the firing rates of cortical neurons, caused for example by reduced NMDA receptor function or reduced spines on neurons, can lead to instability of the high firing rate attractor states that normally implement short-term memory and attention in the prefrontal cortex, contributing to the cognitive symptoms. Reduced NMDA receptor function in the orbitofrontal cortex by reducing firing rates may produce negative symptoms, by reducing reward, motivation, and emotion. Reduced functional connectivity between some brain regions increases the temporal variability of the functional connectivity, contributing to the reduced stability and more loosely associative thoughts. Further, the forward projections have decreased functional connectivity relative to the back projections in schizophrenia, and this may reduce the effects of external bottom-up inputs from the world relative to internal top-down thought processes. Reduced cortical inhibition, caused by a reduction of GABA neurotransmission, can lead to instability of the spontaneous firing states of cortical networks, leading to a noise-induced jump to a high firing rate attractor state even in the absence of external inputs, contributing to the positive symptoms of schizophrenia. In depression, the lateral orbitofrontal cortex non-reward attractor network system is over-connected and has increased sensitivity to non-reward, providing a new approach to understanding depression. This is complemented by under-sensitivity and under-connectedness of the medial orbitofrontal cortex reward system in depression.

Highly active neurons emerging in vitro

Mean firing rates vary across neurons in a neuronal network. Whereas most neurons infrequently emit spikes, a small fraction of neurons exhibit extremely high frequencies of spikes; this fraction of neurons plays a pivotal role in information processing; however, little is known about how these outliers emerge and whether they are maintained over time. In primary cultures of mouse hippocampal neurons, we traced highly active neurons every 24 h for 7 weeks by optically observing the fluorescent protein dVenus; the expression of dVenus was controlled by the promoter of Arc, an immediate early gene that is induced by neuronal activity. Under default-mode conditions, 0.3-0.4% of neurons were spontaneously Arc-dVenus positive, exhibiting high firing rates. These neurons were spatially clustered, exhibited intermittently repeated dVenus expression, and often continued to express Arc-dVenus for approximately two weeks. Thus, highly active neurons constitute a few select functional subpopulations in the neuronal network.

High Firing Temperature GT36 H-Class Low NOx Combustor Engine Validation and Performance

In order to minimize the footprint of human activities on the environment, technologies to reduce greenhouse gases while meeting constantly growing electricity demands are critical. Amongst the various sources of energy production, Gas Turbines (GT) are an efficient way to stabilize the grid with regards to renewable sources like wind and solar energies. The demand for higher efficiency, higher power output while reducing emission levels (especially NO and NO2) at high loads, and for higher flexibility within the H-class Gas Turbine market is thereby a natural consequence. The development and validation of a two-stage sequential combustor, so-called Constant Pressure Sequential Combustion (CPSC) system, to achieve these goals has been accomplished by Ansaldo Energia. The CPSC consists of a premix burner system (First Stage) and of a sequential burner (SB) in series within a can combustor. At the 2017 and 2019 ASME conferences, high pressure test rig validation results of the CPSC were introduced. The advantages with regards to fuel flexibility, hydrogen combustion and low emissions at high firing temperature were presented [1,2,3,4,5]. This article focuses on the validation of the combustor performance in Ansaldo Energia’s Validation Power Plant located in Birr, Switzerland, which includes detailed validation from ignition to full speed no load, part load operation and full load over various ambient and engine thermal state conditions. To allow for detailed validation, dedicated fully instrumented combustor cans were installed in the GT. Detailed validated air distribution and emission models support the results obtained on the engine. Ignition and ramps up to full speed no load have been validated with large variations of the first combustor stage firing temperature to minimize power consumption and start-up time. The potential of the CPSC with regards to turndown capability, with minimum environmental load (MEL) below 25% GT load while keeping CO levels low has been confirmed. The MEL can be kept low over a wide range of ambient temperature and fuel compositions by adjusting the inlet temperature of the sequential burner. Low NOx values were achieved at baseload and peak firing temperature. The operational flexibility and stability of the premixed first stage combustor over the load range and over a large variation of combustor inlet plenum pressures was as well validated along with the operation concept of the gas turbine.

Presynaptic mitochondria volume and abundance increase during development of a high-fidelity synapse

The calyx of Held, a large glutamatergic presynaptic terminal in the auditory brainstem undergoes developmental changes to support the high action-potential firing rates required for auditory information encoding. In addition, calyx terminals are morphologically diverse which impacts vesicle release properties and synaptic plasticity. Mitochondria influence synaptic plasticity through calcium buffering and are crucial for providing the energy required for synaptic transmission. Therefore, it has been postulated that mitochondrial levels increase during development and contribute to the morphological-functional diversity in the mature calyx. However, the developmental profile of mitochondrial volumes and subsynaptic distribution at the calyx of Held remains unclear. To provide insight on this, we developed a helper-dependent adenoviral vector (HdAd) that expresses the genetically encoded peroxidase marker for mitochondria, mito-APEX2, at the mouse calyx of Held. We developed protocols to detect labeled mitochondria for use with serial block face scanning electron microscopy to carry out semi-automated segmentation of mitochondria, high-throughput whole terminal reconstruction and presynaptic ultrastructure in mice of either sex. Subsequently, we measured mitochondrial volumes and subsynaptic distributions at the immature postnatal day 7 (P7) and the mature (P21) calyx. We found an increase of mitochondria volumes in terminals and axons from P7 to P21 but did not observe differences between stalk and swelling subcompartments in the mature calyx. Based on these findings, we propose that mitochondrial volumes and synaptic localization developmentally increase to support high firing rates required in the initial stages of auditory information processing.Significance StatementElucidating the developmental processes of auditory brainstem presynaptic terminals is critical to understanding auditory information encoding. Additionally, morphological-functional diversity at these terminals is proposed to enhance coding capacity. Mitochondria provide energy for synaptic transmission and can buffer calcium, impacting synaptic plasticity; however, their developmental profile to ultimately support the energetic demands of synapses following the onset of hearing remains unknown. Therefore, we created a helper-dependent adenoviral vector with the mitochondria-targeting peroxidase mito-APEX2 and expressed it at the mouse calyx of Held. Volumetric reconstructions of serial block face electron microscopy data of immature and mature labeled calyces reveal that mitochondrial volumes are increased to support high firing rates upon maturity.