An Advanced Ultra-Deep Resistivity Mapping Sensor Reduced Reservoir Uncertainty and Eliminated the Need for a Pilot Hole for the First Time; A Case Study from Offshore Abu Dhabi

The high reservoir uncertainty, due to the lateral distribution of fluids, results in variable water saturation, which is very challenging in drilling horizontal wells. In order to reduce uncertainty, the plan was to drill a pilot hole to evaluate the target zones and plan horizontal sections based on the information gained. To investigate the possibility of avoiding pilot holes in the future, an advanced ultra-deep resistivity mapping sensor was deployed to map the mature reservoirs, to identify formation and fluid boundaries early before penetrating them, avoiding the need for pilot holes. Prewell inversion modeling was conducted to optimize the spacing and firing frequency selection and to facilitate an early real-time geostopping decision. The plan was to run the ultra-deep resistivity mapping sensor in conjunction with shallow propagation resistivity, density, and neutron porosity tools while drilling the 8 ½-in. landing section. The real-time ultra-deep resistivity mapping inversion was run using a depth of inversion up to 120 ft., to be able to detect the reservoir early and evaluate the predicted reservoir resistivity. This would allow optimization of any geostopping decision. The ultra-deep resistivity mapping sensor delivered accurate mapping of low resistivity zones up to 85 ft. TVD away from the wellbore in a challenging low resistivity environment. The real-time ultra-deep resistivity mapping inversion enabled the prediction of resistivity values in target zones prior to entering the reservoir; values which were later crosschecked against open-hole logs for validation. The results enabled identification of the optimal geostopping point in the 8 ½-in. section, enabling up to seven rig days to be saved in the future by eliminating a pilot hole. In addition this would eliminate the risk of setting a whipstock at high inclination with the subsequent impact on milling operations. In specific cases, this minimizes drilling risks in unknown/high reservoir pressure zones by improving early detection of formation tops. Plans were modified for a nearby future well and the pilot-hole phase was eliminated because of the confidence provided by these results. Deployment of the ultra-deep resistivity mapping sensor in these mature carbonate reservoirs may reduce the uncertainty associated with fluid migration. In addition, use of the tool can facilitate precise geosteering to maintain distance from fluid boundaries in thick reservoirs. Furthermore, due to the depths of investigation possible with these tools, it will help enable the mapping of nearby reservoirs for future development. Further multi-disciplinary studies remain desirable using existing standard log data to validate the effectiveness of this concept for different fields and reservoirs.

Kv3 channels contribute to the excitability of sub-populations of spinal cord neurons in lamina VII

Autonomic parasympathetic preganglionic neurons (PGN) drive contraction of the bladder during micturition but remain quiescent during bladder filling. This quiescence is postulated to be due to recurrent inhibition of PGN by fast-firing adjoining interneurons. Here, we defined four distinct neuronal types within lamina VII of the lumbosacral spinal cord, where PGN are situated, by combining whole cell patch clamp recordings with k-means clustering of a range of electrophysiological parameters. Additional morphological analysis separated these neuronal classes into parasympathetic preganglionic populations (PGN) and a fast firing interneuronal population. Kv3 channels are voltage-gated potassium channels (Kv) that allow fast and precise firing of neurons. We found that blockade of Kv3 channels by tetraethylammonium (TEA) reduced neuronal firing frequency and isolated high-voltage-activated Kv currents in the fast-firing population but had no effect in PGN populations. Furthermore, Kv3 blockade potentiated the local and descending inhibitory inputs to PGN indicating that Kv3-expressing inhibitory neurons are synaptically connected to PGN. Taken together, our data reveal that Kv3 channels are crucial for fast and regulated neuronal output of a defined population that may be involved in intrinsic spinal bladder circuits that underpin recurrent inhibition of PGN.

Firing Activities in Fractional-Order Hindmarsh-Rose Neuron with Multistable Memristor as Autapse

Compared with integer order neurons, fractional-order neuron model can more accurately describe the firing behavior of biological neurons. Considering the fact that memristors have the characteristics similar to biological synapses, a fractional-order multistable memristor is firstly proposed in this study. It is verified that the fractional-order memristor has multiple local active regions and multiple stable hysteresis loops, and the influence of fractional order on its nonvolatility is also revealed. Then by considering the fractional-order memristor as an autapse of HR neuron model, a fractional-order memristive neuron model is developed. The effects of the initial value, external excitation current, coupling strength and fractional order on the firing behavior are discussed by time series, phase diagrams, Lyapunov exponents and inter spike interval (ISI) bifurcation diagrams. Three coexisting firing patterns, including irregulate A-periodic bursting, A-periodic bursting and chaotic bursting, dependent on the memristor initial values are observed. It is also revealed that the fractional order can not only induce the transition of firing patterns, but also change the firing frequency of the neuron. Finally, a neuron circuit with variable fractional order is designed to verify the numerical simulations.

Posttranscriptional modulation of KCNQ2 gene expression by the miR-106b microRNA family

MicroRNAs (miRNAs) have recently emerged as important regulators of ion channel expression. We show here that select miR-106b family members repress the expression of the KCNQ2 K+ channel protein by binding to the 3′-untranslated region of KCNQ2 messenger RNA. During the first few weeks after birth, the expression of miR-106b family members rapidly decreases, whereas KCNQ2 protein level inversely increases. Overexpression of miR-106b mimics resulted in a reduction in KCNQ2 protein levels. Conversely, KCNQ2 levels were up-regulated in neurons transfected with antisense miRNA inhibitors. By constructing more specific and stable forms of miR-106b controlling systems, we further confirmed that overexpression of precursor-miR-106b-5p led to a decrease in KCNQ current density and an increase in firing frequency of hippocampal neurons, while tough decoy miR-106b-5p dramatically increased current density and decreased neuronal excitability. These results unmask a regulatory mechanism of KCNQ2 channel expression in early postnatal development and hint at a role for miR-106b up-regulation in the pathophysiology of epilepsy.

Transition from Anti-coherence resonance to coherence resonance for mixed-mode oscillations and period-1 firing of nervous system

Identification of dynamics of the mixed-mode oscillations (MMOs), which exhibit transition between oscillations with large and small amplitudes, is very important for nonlinear physics. In this paper, the MMOs with transition between subthreshold oscillations and spikes are investigated in a neuron model. In the absence of noise, the MMOs appear between the resting state and period-1 firing with increasing depolarization current. After introducing white noise, coherence resonance (CR) is evoked from the resting state and non-CR is induced from period-1 firing far from the MMOs, which is consistent with the traditional viewpoint. However, an interesting result that a transition from anti-CR to CR is evoked by noise from both the MMOs and the period-1 firing near the MMOs is acquired, which is characterized by the increase, decrease and increase again of the coefficient of variations of interspike intervals (ISIs) with increasing noise intensity. At small noise intensity, more subthreshold oscillations are evoked by noise to reduce the firing frequency, resulting in faster increase of standard deviation (SD) of ISIs than that of mean value of ISIs, which is the cause for the anti-CR. The decrease of SD is faster for middle noise intensity and is lower for strong noise intensity, which is the cause for the CR. The different stochastic responses of MMOs and period-1 firing nearby at different levels of noise insanity are the dynamical mechanism for the transition from anti-CR to CR. Such results present potential functions of the MMOs and period-1 firing on information processing in the nervous system with noise and extend the conditions for the CR and anti-CR phenomena, which enriches the contents of nonlinear dynamics.

CaV1.3 L-type Ca2+ channel modulates pancreatic β-cell electrical activity and survival

Pancreatic β cells express several high voltage-gated Ca2+ channel (HVCC) isoforms critical for insulin release, cell differentiation, and survival. RNaseq and qPCR analyses demonstrated that CACNA1D gene encoding for CaV1.3-α1D isoform is highly expressed in pancreatic islets of both mice and men. Additionally, CACNA1D genetic polymorphisms were associated with increased susceptibility for diabetes while CaV1.3 gain-of-function mutations cause hyperinsulinemia in humans. Nevertheless, functional evidence for the role of CaV1.3 on β-cell electrical activity, insulin release, and β-cell mass is contradictory and largely unknown. Here, we show that CaV1.3 deletion led to a sixfold increase in DNA damage and a threefold decrease in proliferation markers in pancreatic β cells of 14-d-old mice, while adult mice were largely unaffected. However, β-cell mass was reduced by ∼20% in both young and old mice, resulting in a diminished sustained insulin release. Voltage-clamp recordings in β-cells of 14-d-old mice showed an ∼20% reduction in total Ca2+ influx (WT Ipeak = −19.76 ± 1.04 pA/pF; CaV1.3−/− Ipeak = −14.84 ± 0.61 pA/pF, P = 0.001) accompanied by slower inactivation and an ∼5 mV rightwards shift in the voltage dependence of activation (WT V1/2 = −7.71 ± 0.82 mV; CaV1.3−/− V1/2 = −2.32 ± 1.09 mV, P = 0.0003). Although to a lower extent, Ca2+ influx in adult CaV1.3−/− β cells was similarly affected. Moreover, current-clamp recordings showed that CaV1.3 deletion delayed the glucose-induced action potential (AP) onset, reduced AP firing frequency (e.g., at 7.5 mM glucose, WT = 4.3 Hz; CaV1.3−/− = 2.1 Hz, P = 0.001) and AP-train frequency (e.g., at 7.5 mM glucose intertrain interval, WT = 49.3 ± 9.6 s; CaV1.3−/− = 120.3 ± 25.5 s, P = 0.04) in both young and adult β cells. Therefore, our data demonstrate that the CaV1.3 channel is required for the initiation of glucose-induced β-cell electrical activity and modulates β-cell mass and insulin release in both young and old mice.

Filtering Properties of Hodgkin-Huxley Neuron to Different Time-Scale Signals

Neuron can be excited and inhibited by filtered signals. The filtering properties of neural networks have a huge impact on memory, learning, and disease. In this paper, the filtering properties of Hodgkin-Huxley neuron to different time-scale signals are investigated. It is found that the neuronal filtering property depends on the locking relationship between the signal's frequency band and the natural frequency of neuron. The natural firing frequency is a combination of the fundamental component and the various level harmonic components. The response of neuron to the filtered signal is related to the amplitude of the harmonic components. Neuron responds better to the low-frequency signals than the high-frequency signals because of the reduction in the harmonic component amplitude. The filtering ability of neuron can be modulated by the excitation level, and is stronger around the excitation threshold. Our results might provide novel insights into the filtering properties of neural networks and guide the construction of artificial neural networks.

Fasciculation differences between ALS and non-ALS patients: an ultrasound study

Background Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. Methods Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. Results The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0–3) in ALS and 0 (0–0) in non-ALS patients (P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs. Discussion The fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients. Conclusions The fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.

Long-Term Inactivation of Sodium Channels as a Mechanism of Adaptation in CA1 Pyramidal Neurons

The hippocampus is involved in memory and spatial navigation. Many CA1 pyramidal cells function as place cells, increasing their firing rate when a specific place field is traversed. The dependence of CA1 place cell firing on position within the place field is asymmetric. We investigated the source of this asymmetry by injecting triangular depolarizing current ramps to approximate the spatially-tuned, temporally-diffuse depolarizing synaptic input received by these neurons while traversing a place field. Ramps were applied to rat CA1 pyramidal neurons in vitro (slice electrophysiology) and in silico (multi-compartmental NEURON model). Under control conditions, CA1 neurons fired more action potentials at higher frequencies on the up-ramp versus the down-ramp. This effect was more pronounced for dendritic compared to somatic ramps. We incorporated a five-state Markov scheme for NaV1.6 channels into our model and calibrated the spatial dependence of long-term inactivation according to the literature; this spatial dependence was sufficient to explain the difference in dendritic versus somatic ramps. Long-term inactivation reduced the firing frequency by decreasing open-state occupancy, and reduced spike amplitude during trains by decreasing occupancy in closed states, which comprise the available pool. PKC activators like phorbol ester phorbol-dibutyrate (PDBu) are known to reduce NaV long-term inactivation. PDBu application removed spike amplitude attenuation during spike trains in vitro, more visibly in dendrites, consistent with decreased NaV long-term inactivation. Moreover, PDBu greatly reduced adaptation, consistent with our hypothesized mechanism. Our synergistic experimental/computational approach shows that long-term inactivation of NaV1.6 is the primary mechanism of adaptation in CA1 pyramidal cells.

Activity of Cerebellar Nuclei Neurons Correlates with ZebrinII Identity of Their Purkinje Cell Afferents

Purkinje cells (PCs) in the cerebellar cortex can be divided into at least two main subpopulations: one subpopulation that prominently expresses ZebrinII (Z+), and shows a relatively low simple spike firing rate, and another that hardly expresses ZebrinII (Z–) and shows higher baseline firing rates. Likewise, the complex spike responses of PCs, which are evoked by climbing fiber inputs and thus reflect the activity of the inferior olive (IO), show the same dichotomy. However, it is not known whether the target neurons of PCs in the cerebellar nuclei (CN) maintain this bimodal distribution. Electrophysiological recordings in awake adult mice show that the rate of action potential firing of CN neurons that receive input from Z+ PCs was consistently lower than that of CN neurons innervated by Z– PCs. Similar in vivo recordings in juvenile and adolescent mice indicated that the firing frequency of CN neurons correlates to the ZebrinII identity of the PC afferents in adult, but not postnatal stages. Finally, the spontaneous action potential firing pattern of adult CN neurons recorded in vitro revealed no significant differences in intrinsic pacemaking activity between ZebrinII identities. Our findings indicate that all three main components of the olivocerebellar loop, i.e., PCs, IO neurons and CN neurons, operate at a higher rate in the Z– modules.