Slow Firing Research Articles

Thermodynamics in the system "refractory clay–glass cullet–quartz sand" when predicting the phase composition of engobe coatings on ceramic bricks

A thermodynamic analysis of the reactions involved in the formation of the phase composition of engobe coatings in the system "refractory clay–glass cullet–quartz sand" on ceramic bricks during firing has been performed. The study highlights the features of glass crystallization during prolonged exposure within the temperature range of 690–7700C, characteristic of the slow firing process in industrial ceramic brick production. Devitrite and -cristobalite are identified as the primary crystalline phases formed in the cullet, playing an active role in solid-phase reactions that shape the structure of the engobe coatings. The phase composition of the coatings depends on the maximum firing temperature and is influenced by the thermal transformation products of the raw materials (metakaolin, mullite, devitrite, -wollastonite) as well as the crystalline phases generated through chemical interactions between the engobe components. Among the significant phases formed, anorthite and -cristobalite are particularly notable for contributing to the strength and hardness of the brick's covering layer. The findings of this work provide a foundation for designing engobe compositions and selecting technological parameters to achieve coatings with superior performance characteristics.

Endoplasmic Reticulum and Mitochondrial Calcium Handling Dynamically Shape Slow Afterhyperpolarizations in Vasopressin Magnocellular Neurons.

Many neurons including vasopressin (VP) magnocellular neurosecretory cells (MNCs) of the hypothalamic supraoptic nucleus (SON) generate afterhyperpolarizations (AHPs) during spiking to slow firing, a phenomenon known as spike frequency adaptation. The AHP is underlain by Ca2+-activated K+ currents, and while slow component (sAHP) features are well described, its mechanism remains poorly understood. Previous work demonstrated that Ca2+ influx through N-type Ca2+ channels is a primary source of sAHP activation in SON oxytocin neurons, but no obvious channel coupling was described for VP neurons. Given this, we tested the possibility of an intracellular source of sAHP activation, namely, the Ca2+-handling organelles endoplasmic reticulum (ER) and mitochondria in male and female Wistar rats. We demonstrate that ER Ca2+ depletion greatly inhibits sAHPs without a corresponding decrease in Ca2+ signal. Caffeine sensitized AHP activation by Ca2+ In contrast to ER, disabling mitochondria with CCCP or blocking mitochondria Ca2+ uniporters (MCUs) enhanced sAHP amplitude and duration, implicating mitochondria as a vital buffer for sAHP-activating Ca2+ Block of mitochondria Na+-dependent Ca2+ release via triphenylphosphonium (TPP+) failed to affect sAHPs, indicating that mitochondria Ca2+ does not contribute to sAHP activation. Together, our results suggests that ER Ca2+-induced Ca2+ release activates sAHPs and mitochondria shape the spatiotemporal trajectory of the sAHP via Ca2+ buffering in VP neurons. Overall, this implicates organelle Ca2+, and specifically ER-mitochondria-associated membrane contacts, as an important site of Ca2+ microdomain activity that regulates sAHP signaling pathways. Thus, this site plays a major role in influencing VP firing activity and systemic hormonal release.

Deep learning models for atypical serotonergic cells recognition

Background:The serotonergic system modulates brain processes via functionally distinct subpopulations of neurons with heterogeneous properties, including their electrophysiological activity. In extracellular recordings, serotonergic neurons to be investigated for their functional properties are commonly identified on the basis of “typical” features of their activity, i.e. slow regular firing and relatively long duration of action potentials. Thus, due to the lack of equally robust criteria for discriminating serotonergic neurons with “atypical” features from non-serotonergic cells, the physiological relevance of the diversity of serotonergic neuron activities results largely understudied. New Methods: We propose deep learning models capable of discriminating typical and atypical serotonergic neurons from non-serotonergic cells with high accuracy. The research utilized electrophysiological in vitro recordings from serotonergic neurons identified by the expression of fluorescent proteins specific to the serotonergic system and non-serotonergic cells. These recordings formed the basis of the training, validation, and testing data for the deep learning models. The study employed convolutional neural networks (CNNs), known for their efficiency in pattern recognition, to classify neurons based on the specific characteristics of their action potentials. Results:The models were trained on a dataset comprising 27,108 original action potential samples, alongside an extensive set of 12 million synthetic action potential samples, designed to mitigate the risk of overfitting the background noise in the recordings, a potential source of bias. Results show that the models achieved high accuracy and were further validated on ”non-homogeneous” data, i.e., data unknown to the model and collected on different days from those used for the training of the model, to confirm their robustness and reliability in real-world experimental conditions. Comparison with existing methods: Conventional methods for identifying serotonergic neurons allow recognition of serotonergic neurons defined as typical. Our model based on the analysis of the sole action potential reliably recognizes over 94% of serotonergic neurons including those with atypical features of spike and activity. Conclusion:The model is ready for use in experiments conducted with the here described recording parameters. We release the codes and procedures allowing to adapt the model to different acquisition parameters or for identification of other classes of spontaneously active neurons.

Effect of firing process on electrical properties and efficiency of n-TOPCon solar cells

In the large-scale production of solar cells, metallization is a very important process, which directly affects the opening-circuit voltage, short-cut current, shunt resistance, and fill factor, thus affecting the efficiency of the solar cell. In this paper, the n-TOPCon process is matched by changing the firing temperature and belt speed of each zone to change the peak temperature and the width of the firing curve. After low-temperature slow firing (A1), the front contact resistance of the solar cell is the largest, and the Uoc and the Eff are the highest. However, after the electric injection, the Uoc and the FF increase are small, and the Eff is low, with an average value of 24.23 % and an increase of 0.04 %. After higher temperature and faster firing (AB2), the front-specific contact resistance of the solar cell is the smallest. Affected by the specific contact resistance, the solar cell has the highest FF, the lowest Uoc, and the lowest Eff. However, the electrical injection significantly increases the Uoc. The Eff after electric injection is the highest, with an average of 24.42 %, an increase of 0.36 %. The H ions in SiNx have different effects of passivation on the wafer under different firing conditions, but the difference is narrowed by the electrical carrier injection of H ions on the surface into the wafer. Therefore, solar cells with excellent electrical performance can be obtained by firing at appropriate peak temperature and firing width, obtaining low contact resistance first, and then increasing the Uoc and Jsc by electric injection.

Laparoscopic radical antegrade modular pancreatosplenectomy for pancreatic cancer: technical tips and pitfalls

: Laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) has been increasingly performed for pancreatic ductal adenocarcinoma (PDAC) in the body and tail of the pancreas. However, it is technically demanding, and a lack of experience can lead to serious intraoperative and postoperative complications or local recurrence due to residual tumors at the surgical margins. There are three keys to successful L-RAMPS: understanding anatomical variations; obtaining appropriate operative fields; and familiarity with several approaches. Preoperative evaluation should be focused not only on the tumor characteristics but also on the anatomical variations of major vessels. Surgeons should choose the appropriate approach according to the tumor location and anatomical variations for each patient. Retracting the liver and stomach is crucial for obtaining appropriate operative fields around the pancreas. Optimizing the caudal view of laparoscopy is important for safe approaches to the major vessels. Adequate posterior dissection according to the extent of retropancreatic invasion and en bloc regional lymphadenectomy should be performed for oncological benefits. Additionally, proper pancreatic transection with precompression of the pancreas, adequate selection of the cartridge of stapler, and slow firing technique is crucial for the prevention of postoperative pancreatic fistulas. A review of the literature was performed and our standard L-RAMPS technique was described.

Proximal dendritic localization of NALCN channels underlies tonic and burst firing in nigral dopaminergic neurons.

In multipolar nigral dopamine (DA) neurons, the highly excitable proximal dendritic compartments (PDCs) and two Na+ -permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. However, the causal link between them is unknown. Here we report that the proximal dendritic localization of NALCN underlies pacemaking and burst firing in DA neurons. Our morphological analysis of nigral DA neurons reveals that TRPC3 is ubiquitously expressed in the whole somatodendritic compartment, but NALCN is localized within the PDCs. Blocking either TRPC3 or NALCN channels abolished pacemaking. However, only blocking NALCN, not TRPC3, degraded burst discharges. Furthermore, local glutamate uncaging readily induced burst discharges within the PDCs, compared with other parts of the neuron, and NALCN channel inhibition dissipated burst generation, indicating the importance of NALCN to the high excitability of PDCs. Therefore, we conclude that PDCs serve as a common base for tonic and burst firing in nigral DA neurons. KEY POINTS: Midbrain dopamine (DA) neurons are slow pacemakers that can generate tonic and burst firings, and the highly excitable proximal dendritic compartments (PDCs) and two Na+ -permeable leak channels, TRPC3 and NALCN, play a key role in pacemaking. We find that slow tonic firing depends on the basal activity of both the NALCN and TRPC3 channels, but that burst firing does not require TRPC3 channels but relies only on NALCN channels. We find that TRPC3 is ubiquitously expressed in the entire somatodendritic compartment, but that NALCN exists only within the PDCs in nigral DA neurons. We show that NALCN channel localization confers high excitability on PDCs and is essential for burst generation in nigral DA neurons. These results suggest that PDCs serve as a common base for tonic and burst firing in nigral DA neurons.

Glycolysis regulates neuronal excitability via lactate receptor, HCA1R.

Repetitively firing neurons during seizures accelerate glycolysis to meet energy demand, which leads to the accumulation of extracellular glycolytic by-product lactate. Here, we demonstrate that lactate rapidly modulates neuronal excitability in times of metabolic stress via the hydroxycarboxylic acid receptor type 1 (HCA1R) to modify seizure activity. The extracellular lactate concentration, measured by a biosensor, rose quickly during brief and prolonged seizures. In two epilepsy models, mice lacking HCA1R (lactate receptor) were more susceptible to developing seizures. Moreover, HCA1R deficient (knockout) mice developed longer and more severe seizures than wild-type littermates. Lactate perfusion decreased tonic and phasic activity of CA1 pyramidal neurons in genetically encoded calcium indicator 7 imaging experiments. HCA1R agonist 3-chloro-5-hydroxybenzoic acid (3CL-HBA) reduced the activity of CA1 neurons in HCA1R WT but not in knockout mice. In patch-clamp recordings, both lactate and 3CL-HBA hyperpolarized CA1 pyramidal neurons. HCA1R activation reduced the spontaneous excitatory postsynaptic current frequency and altered the paired-pulse ratio of evoked excitatory postsynaptic currents in HCA1R wild-type but not in knockout mice, suggesting it diminished presynaptic release of excitatory neurotransmitters. Overall, our studies demonstrate that excessive neuronal activity accelerates glycolysis to generate lactate, which translocates to the extracellular space to slow neuronal firing and inhibit excitatory transmission via HCA1R. These studies may identify novel anticonvulsant target and seizure termination mechanisms.

Slow Firing Single Units Are Essential for Optimal Decoding of Silent Speech.

The motivation of someone who is locked-in, that is, paralyzed and mute, is to find relief for their loss of function. The data presented in this report is part of an attempt to restore one of those lost functions, namely, speech. An essential feature of the development of a speech prosthesis is optimal decoding of patterns of recorded neural signals during silent or covert speech, that is, speaking “inside the head” with output that is inaudible due to the paralysis of the articulators. The aim of this paper is to illustrate the importance of both fast and slow single unit firings recorded from an individual with locked-in syndrome and from an intact participant speaking silently. Long duration electrodes were implanted in the motor speech cortex for up to 13 years in the locked-in participant. The data herein provide evidence that slow firing single units are essential for optimal decoding accuracy. Additional evidence indicates that slow firing single units can be conditioned in the locked-in participant 5 years after implantation, further supporting their role in decoding.

Hidden hearing loss: current concepts.

The purpose of this review is to offer a concise summary of current knowledge regarding hidden hearing loss (HHL) and to describe the variety of mechanisms that contribute to its development. We will also discuss the various diagnostic tools that are available as well as future directions. Hidden hearing loss often also called cochlear synaptopathy affects afferent synapses of the inner hair cells. This description is in contrast to traditional models of hearing loss, which predominantly affects auditory hair cells. In HHL, the synapses of nerve fibres with a slow spontaneous firing rate, which are crucial for locating sound in background noise, are severely impaired. In addition, recent research suggests that HHL may also be related to cochlear nerve demyelination. Noise exposure causes loss of myelin sheath thickness. Auditory brainstem response, envelope-following response and middle-ear muscle reflex are promising diagnostic tests, but they have yet to be validated in humans. Establishing diagnostic tools for cochlear synaptopathy in humans is important to better understand this patient population, predict the long-term outcomes and allow patients to take the necessary protective precautions.

Heterogeneity in form and function of the rat extensor digitorum longus motor unit.

The motor unit comprises a variable number of muscle fibres that connect through myelinated nerve fibres to a motoneuron (MN), the central drivers of activity. At the simplest level of organisation there exist phenotypically distinct MNs that activate corresponding muscle fibre types, but within an individual motor pool there typically exists a mixed population of fast and slow firing MNs, innervating groups of Type II and Type I fibres, respectively. Characterising the heterogeneity across multiple levels of motor unit organisation is critical to understanding changes that occur in response to physiological and pathological perturbations. Through a comprehensive assessment of muscle histology and ex vivo function, mathematical modelling and neuronal tracing, we demonstrate regional heterogeneities at the level of the MN, muscle fibre type composition and oxygen delivery kinetics of the rat extensor digitorum longus (EDL) muscle. Specifically, the EDL contains two phenotypically distinct regions: a relatively oxidative medial and a more glycolytic lateral compartment. Smaller muscle fibres in the medial compartment, in combination with a greater local capillary density, preserve tissue O2 partial pressure (PO2) during modelled activity. Conversely, capillary supply to the lateral compartment is calculated to be insufficient to defend active muscle PO2 but is likely optimised to facilitate metabolite removal. Simulation of in vivo muscle length change and phasic activation suggest that both compartments are able to generate similar net power. However, retrograde tracing demonstrates (counter to previous observations) that a negative relationship between soma size and C‐bouton density exists. Finally, we confirm a lack of specificity of SK3 expression to slow MNs. Together, these data provide a reference for heterogeneities across the rat EDL motor unit and re‐emphasise the importance of sampling technique.

Dynamics of synaptically coupled FitzHugh–Nagumo neurons

An extended FitzHugh–Nagumo model is developed to model the synaptic coupling of neurons and the associated dynamics. The neurons are coupled via chemical synapses, which can excite or inhibit the postsynaptic neuron. The neurotransmitter–receptor dynamics is governed with a gating dynamic, which allows for the distinction between fast and slow synapses. Detailed nonlinear dynamics analysis are performed for simple neural motifs of a self-synapsed neuron and two synaptically coupled neurons for the instabilities that lead to neural oscillations, and the associated phase diagrams are obtained. Interesting dynamics such as synchronization of fast and slow firing neurons, frequency enhancement, quiescent neurons coupled to oscillators, chaotic spiking, and periodic bursting are found.

Channel block of the astrocyte network connections accounting for the dynamical transition of epileptic seizures

Epilepsy has been found to be modulated by the astrocyte systems in experiments, and tremendous modeling studies have unveiled the roles of astrocyte cellular functions such as the calcium and potassium channels in the epileptic seizures. However, little attention has been paid to the structure changes of astrocytes in the epileptic seizures in the scale of networks. This paper first constructs a neuron–astrocyte network model to explain the experimental observation that astrocytes mainly induce epilepsy by blocking the channels of the astrocyte gap junction in the network scale. Such model is used to discuss potential seizure induction process in the network by changing the connection intensity of the astrocyte gap junction. The simulation results show that a decrease of the gap junction intensity changes the firing pattern of the population of neurons from slow periodical firing to high-frequency epileptic seizures, featuring epileptic patterns of depolarization blocks. This further verifies that epileptic seizures are experimentally induced via the channel block of the astrocyte gap junctions. Because of the heterogeneous structure of the real neuron–astrocyte network, the effect of changing astrocyte network structures on the seizure activities is then studied in two typical network structures: the regular neighboring connection and the random connection. The results show that an increase of the number of regular connections of the regular neighboring astrocyte network could inhibit the induction and spread of the epileptic seizures. The epileptic inhibition can be achieved similarly by increasing the connection probability of the random astrocyte network. These findings further provide evidence for the experimental phenomena of the protective response of gliosis to epilepsy with increasing gap junctions. Above all, the simulation results suggest a potential pathway of epilepsy treatment by targeting the astrocyte gap junctions.

Efficacy of the slow firing method using a reinforced triple-row stapler for preventing postoperative pancreatic fistula during laparoscopic distal pancreatectomy.

Postoperative pancreatic fistula (POPF) remains the most clinically relevant complication of laparoscopic distal pancreatectomy (LDP). The present study evaluated the efficacy of the "slow firing method" using a reinforced triple-row stapler (Covidien, Tokyo, Japan) during LDP. This retrospective single-center study included 73 consecutive patients who underwent LDP using the slow firing method. A black cartridge was used in all patients. The primary endpoint was the rate of clinically relevant POPF (CR-POPF) after LDP. Secondary endpoints included perioperative outcomes and factors associated with CR-POPF as well as the correlation between the transection time and thickness of the pancreas. Four patients (5.5%) developed CR-POPF (grade B). Overall morbidity rates, defined as grade ≥ II and ≥ III according to the Clavien-Dindo classification, were 21 and 11%, respectively. The median postoperative hospital stay was 10days. Preoperative diabetes (13.6 vs. 0.2%, P = 0.044) and thickness of the pancreas ≥ 15mm (13.8% vs. 0%, P = 0.006) were identified as independent risk factors for CR-POPF. The median transection time was 16 (8-29)min. The slow firing method using a reinforced triple-row stapler for pancreatic transection is simple, safe, and effective for preventing CR-POPF after LDP.

Discharge characteristics of neurons of nucleus reuniens across sleep-wake states in the behaving rat

The nucleus reuniens (RE) of the ventral midline thalamus is strongly reciprocally connected with the hippocampus (HF) and medial prefrontal cortex (PFC), serving a critical role in affective and cognitive functioning. While midline thalamic nuclei have been implicated in the modulation of states of arousal and consciousness, few studies have addressed RE’s role in behavioral state control. Accordingly, as a first line of investigation, we examined the discharge properties of RE neurons in behaving rats throughout the sleep-wake cycle. We analyzed 153 units in RE which demonstrated heterogeneity in discharge rates and pattern of activity across sleep wake states. Using a rate ratio of activity in wake vs. REM, we found that the majority of cells displayed state-related changes and were classified into distinct cell types, exhibiting their highest discharge rates during active waking (AW), REM sleep, or maintaining equivalent activity across AW/REM. We further distinguished cells as either slow firing (SF = < 10 Hz) or fast firing (FF =>10 Hz) cells. The majority of cells, independent of state-related preference, were SF. FF RE cells were primarily wake active and wake/REM cell types. This diverse set of RE neurons are likely modulated by key brainstem and hypothalamic nuclei, which in turn, drive RE to exert strong effects on its cortical targets during waking and REM sleep. RE may not only act as a node in HF-PFC circuitry, but also as a critical thalamic link in ascending arousal and attentional networks.

Fast inactivation of Nav1.3 channels by FGF14 proteins: An unconventional way to regulate the slow firing of adrenal chromaffin cells.

Using Nav1.3 and FGF14 KO mice, Martinez-Espinosa et al. provide new findings on how intracellular FGF14 proteins interfere with the endogenous fast inactivation gating and regulate the “long-term inactivation” of Nav1.3 channels that sets Nav channel availability and spike adaptation during sustained stimulation in adrenal chromaffin cells.

A stimulating life and career – an obituary for Professor Gerta Vrbová

A stimulating life and career – an obituary for Professor Gerta Vrbová

Atypical fibrillation and fasciculation potentials: An exercise in waveform identification and analysis.

No consensus criteria exist for recording and analyzing waveforms in clinical electromyography (EMG). There have been significant technical improvements in recent decades that are under-used in both routine practice and research. In current practice, disciplined techniques in acquisition and analysis of signals are required to appropriately define them. As an example, we describe such an exercise in acquisition and analysis. During a routine study, atypical spontaneous activity was encountered. High-quality digital recordings were stored for off-line analysis. These revealed waveforms that could be isolated and quantitatively defined using basic instrumentation available on most modern EMG systems: "slow" firing fibrillation potentials and a repeating fasciculation potential. Subjective analysis alone could not have identified them. To improve accuracy in identification and understanding of these waveforms, we propose criteria for data collection and signal analysis. This is critical for quality in routine practice, education, and proper reporting of electrophysiological signals.

Development of Adhesive, Bioactive and Antibacterial Titania Sol-Gel Coating on Titanium Substrate by Dip-Coating Technique

The sol-gel method provides a wide variety of applications in the medical field. One of these applications is the formation of coatings on the metal implants. The coatings containing specific additive can enhance or improve the existing surface properties of the substrate. In this work, titania sol-gel coatings were doped with two forms of silver (AgNO3, Ag3PO4) and synthetic hydroxyapatite and applied on the titanium samples by dip-coating technique. After drying and slow firing, all coatings were characterized with scanning electron microscopy. Thin coatings were successfully prepared with excellent adhesion to the substrate (measured by ASTM D 3359-2), despite cracks. Coatings containing silver and hydroxyapatite demonstrated a 100% antibacterial effect against Escherichia coli after 24 h. The bioactivity of the coatings containing hydroxyapatite tested in modified simulated body fluid under static-dynamic conditions was confirmed by bone-like hydroxyapatite precipitation. To better understand the interaction of the coatings with simulated body fluid (SBF), changes of Ca2+ and (PO4)3− ions concentrations and pH values were studied.

Detached from reality.

A dissociative state is caused by slow rhythmic firing of deep neurons in the retrosplenial cortex in mice or the homologous posteromedial cortex in humans

Context-Dependent Multiplexing by Individual VTA Dopamine Neurons.

Dopamine (DA) neurons of the VTA track cues and rewards to generate a reward prediction error signal during Pavlovian conditioning. Here we explored how these neurons respond to a self-paced, operant task in freely moving mice. The animal could trigger a reward-predicting cue by remaining in a specific location of an operant box for a brief time before moving to a spout for reward collection. VTA DA neurons were identified using DAT-Cre male mice that carried an optrode with minimal impact on the behavioral task. In vivo single-unit recordings revealed transient fast spiking responses to the cue and reward in correct trials, while for incorrect ones the activity paused, reflecting positive and negative error signals of a reward prediction. In parallel, a majority of VTA DA neurons simultaneously encoded multiple actions (e.g., movement velocity, acceleration, distance to goal, and licking) in sustained slow firing modulation. Applying a GLM, we show that such multiplexed encoding of rewarding and motor variables by individual DA neurons was only apparent while the mouse was engaged in the task. Downstream targets may exploit such goal-directed multiplexing of VTA DA neurons to adjust actions to optimize the task's outcome.SIGNIFICANCE STATEMENT VTA DA neurons code for multiple functions, including the reward prediction error but also motivation and locomotion. Here we show that about half of the recorded VTA DA neurons perform multiplexing: they exploit the phasic and tonic activity modes to encode, respectively, the cue/reward responses and motor parameters, most prominently when the mouse engages in a self-paced operand task. VTA non-DA neurons, by contrast, encode motor parameters regardless of task engagement.