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Objective To summarize the electrophysiological and muscle pathological characteristics of Lambert - Eaton myasthenic syndrome (LEMS). Methods and Results Twelve LEMS patients referred to China - Japan Friendship Hospital between January 2010 and December 2021 were included. Clinically, they all showed proximal muscle weakness and reduced or disappeared tendon reflexes. Electrophysiologically, all 12 patients showed decreased compound muscle action potential (CMAP) amplitudes, normal distal motor latency (DML), and normal motor and sensory conduction velocities. Ten patients underwent repetitive nerve stimulation (RNS) test: all had amplitude increments of more than 100% at high - frequency RNS, and 8 had amplitude decrements of more than 15% at low - frequency RNS. Three patients completed the post-exercise facilitation (PEF) test: the ulnar nerve CMAP amplitude reached a peak immediately after maximum voluntary contraction of the abductor digiti minimi for 5-10 s and then gradually decreased to near baseline level after contraction for 60 s; the ulnar nerve CMAP amplitude reached a peak immediately after maximum voluntary contraction for 10 s, and then rapidly decreased to near baseline level after 15 s. On needle EMG, 8 patients showed normal motor unit action potential (MUAP), 3 showed short - duration MUAP mimicking myopathy, and one showed long - duration MUAP mimicking neuropathy. Two patients with normal MUAP underwent biceps biopsy, which showed selective type Ⅱ fiber atrophy. Conclusions Electrophysiologically, CMAP amplitudes of LEMS patients are usually diffusely low or borderline. LEMS patients have amplitude increments of more than 100% at high-frequency RNS, and some have amplitude decrements of more than 15% at low-frequency RNS. PEF test shows a transient but significant CMAP amplitude increase after 5-10 s maximum voluntary contraction. Needle EMG is usually normal, but some show myogenic lesions, and some show neurogenic lesions. Muscle biopsy shows selective type Ⅱ fiber atrophy. Needle EMG myogenic lesion may not be associated with pathologically selective type Ⅱ fiber atrophy.

Abstract Engineered biological neural networks are indispensable models for investigation of neural function and dysfunction from the subcellular to the network level. Notably, advanced neuroengineering approaches are of significant interest for their potential to replicate the topological and functional organization of brain networks. In this study, we reverse engineered feedforward neural networks of primary cortical and hippocampal neurons, using a custom-designed multinodal microfluidic device with Tesla valve inspired microtunnels. By interfacing this device with nanoporous microelectrodes, we show that the reverse engineered multinodal neural networks exhibit capacity for both segregated and integrated functional activity, mimicking brain network dynamics. To advocate the broader applicability of our model system, we induced localized perturbations with amyloid beta to study the impact of pathology on network functionality. Additionally, we demonstrate long-term culturing of subregion- and layer specific neurons extracted from the entorhinal cortex and hippocampus of adult Alzheimer’s-model mice and rats. Our results thus highlight the potential of our approach for reverse engineering of anatomically relevant multinodal neural networks to study dynamic structure-function relationships in both healthy and pathological conditions.

Background: Increasingly valuable, sophisticated, and powerful aircraft are developed and incorporated into the armed forces. Technological advances are notable for increasing physiological load during the flight, making human resources a limiting factor in such operations. It is necessary to understand the physiological demands to which aircraft pilots are exposed, especially combat pilots. Objective: This study aimed to present: i. the physiological consequences on the human body due to high accelerative forces during high-performance flights; ii. the efficiency of the Anti-G Straining Maneuver (AGSM) countermeasure to such consequences; and iii. the state of the art about surface electromyography's uses (sEMG) in AGSM. Method: It was conducted a bibliographic search in the PubMed database using the keywords “anti-G effort maneuver” and “electromyography” and their synonyms. After this, a narrative review of the results was performed. This research model allows a comprehensive discussion about the topic, enabling an in-depth contextualization in a prosperous field of study. These characteristics are suitable for detecting literature gaps and directing the research discussion. Discussion: There is a consensus in the literature that AGSM is the most effective resource to prevent loss of consciousness induced by G-load (G-LOC). The sEMG is an affordable and useful tool for AGSM training, especially given the unavailability of human centrifuges. The current literature on the application of sEMG in the context of AGSM training is limited, presenting a diversity of objectives, methodology, and analyzed parameters. Conclusion: The use of sEMG as real-time biofeedback can improve the pilot's muscle control skills during AGSM.

The global health concern of pharmacoresistant epilepsy necessitates innovative therapeutic strategies. Drug resistance often arises due to complex pharmacokinetic challenges. Beta-cyclodextrin, known for enhancing drug solubility and stability, offers a potential solution for improving the efficacy of antiseizure medications. This study aims to investigate the impact of beta-cyclodextrin-complexed rufinamide on seizure-like activity using an in vitro model of temporal lobe epilepsy.

Robotic technology is one of the most dynamically evolving fields in medicine. Alongside technological advancement, there is a growing demand for automated functions aimed at preventing human errors. The application of robotic technologies in cardiology, especially in electrophysiology, is becoming increasingly widespread. Robots enable more precise and safer interventions, overcoming the limitations of manual methods. This review primarily focuses on describing the most widely available cardiac robotic technology at present, the robotic magnetic navigation system (RMN). The RMN system offers numerous advantages during catheter ablation procedures, including reduced fluoroscopy exposure, decreased incidence of complications, and improved acute and long-term success rates. RMN is a valuable tool in the treatment of complex arrhythmias, as well as in patients with congenital heart defects or those who have undergone previous surgical interventions. Its exceptional image integration capabilities and precise catheter navigation offer a safe and effective solution in the field of electrophysiology.

Abstract Introduction Closed-loop spinal cord stimulation (CL-SCS) is a recently introduced system that records evoked compound action potentials (ECAPs) from the spinal cord elicited by each stimulation pulse and uses this information to automatically adjust the stimulation strength in real time, known as ECAP-controlled SCS. This innovative system compensates for fluctuations in the distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a predetermined target level. This data collection study was designed to assess the performance of the first CL-SCS system in a real-world setting under normal conditions of use in multiple European centers. The study analyzes and presents clinical outcomes and electrophysiological and device data and compares these findings with those reported in earlier pre-market studies of the same system. Methods This prospective, multicenter, observational study was conducted in 13 European centers and aimed to gather electrophysiological and device data. The study focused on the real-world application of this system in treating chronic pain affecting the trunk and/or limbs, adhering to standard conditions of use. In addition to collecting and analyzing basic demographic information, the study presents data from the inaugural patient cohort permanently implanted at multiple European centers. Results A significant decrease in pain intensity was observed for overall back or leg pain scores (verbal numerical rating score [VNRS]) between baseline (mean ± standard error of the mean [SEM]; n = 135; 8.2 ± 0.1), 3 months (n = 93; 2.3 ± 0.2), 6 months (n = 82; 2.5 ± 0.3), and 12 months (n = 76; 2.5 ± 0.3). Comparison of overall pain relief (%) to the AVALON and EVOKE studies showed no significant differences at 3 and 12 months between the real-world data release (RWE; 71.3%; 69.6%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies. Further investigation was undertaken to objectively characterize the physiological parameters of SCS therapy in this cohort using the metrics of percent time above ECAP threshold (%), dose ratio, and dose accuracy (µV), according to previously described methods. Results showed that a median of 90% (40.7–99.2) of stimuli were above the ECAP threshold, with a dose ratio of 1.3 (1.1–1.4) and dose accuracy of 4.4 µV (0.0–7.1), based on data from 236, 230, and 254 patients, respectively. Thus, across all three metrics, the majority of patients had objective therapy metrics corresponding to the highest levels of pain relief in previously reported studies (usage over threshold > 80%, dose ratio > 1.2, and error

Functional tremor is the most common subtype of functional movement disorder (FMD). At present, there is no "gold standard" for diagnosis. Most clinical manifestations coincide with organic tremor, which can easily lead to misdiagnosis and mistreatment. Characteristic electrophysiological manifestations can provide objective and repeatable diagnostic information, effectively supplement the history and physical examination, and can also be used in the differential diagnosis from organic tremor. This article reviews the electrophysiological characteristics of functional tremor and its application in diagnosis and differential diagnosis, in order to improve the clinical understanding of this disease.

Abstract The red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier), also known as the Asian palm weevil, is an invasive pest that causes widespread damage to palm trees around the globe. As pheromone communication is crucial for their mass attack and survival on palm trees, the olfactory concept of pest control strategies has been widely explored recently. We aim to understand the molecular basis of olfaction in RPW by studying one of the key olfactory proteins in insect pheromone communication, sensory neuron membrane proteins (SNMPs). SNMPs belong to the CD36 (cluster of differentiation 36) family that perform two distinct olfactory roles in insects, either in pheromone (odorant) transfer to the odorant receptors (SNMP1) or in the pheromone clearing process (SNMP2). In this study, we performed antennal transcriptomic screening and identified six SNMPs, mapping them on the R. ferrugineus genome, and confirmed four distinct SNMPs. Both SNMP1 proteins in RPW, viz., RferSNMPu1 and RferSNMPu2, were mapped onto the same scaffold in different loci in the RPW genome. To further understand the function of these proteins, we first classified them using phylogenetic analysis and checked their tissue-specific expression patterns. Further, we measured the relative transcript abundance of SNMPs in laboratory-reared, field-collected adults and pheromone-exposure experiments, ultimately identifying RferSNMPu1 as a potential candidate for functional analysis. We mapped RferSNMPu1 expression in the antennae and found that expression patterns were similar in both sexes. We used RNAi-based gene silencing to knockdown RferSNMPu1 and tested the changes in the RPW responses to aggregation pheromone compounds, 4-methyl-5-nonanol (ferrugineol) and 4-methyl-5-nonanone (ferrugineone), and a kairomone, ethyl acetate using electroantennogram (EAG) recordings. We found a significant reduction in the EAG recordings in the RferSNMPu1 knockdown strain of adult RPWs, confirming its potential role in pheromone detection. The structural modelling revealed the key domains in the RferSNMPu1 structure, which could likely be involved in pheromone detection based on the identified ectodomain tunnels. Our studies on RferSNMPu1 with a putative role in pheromone detection provide valuable insight into understanding the olfaction in R. ferrugineus as well as in other Curculionids, as SNMPs are under-explored in terms of its functional role in insect olfaction. Most importantly, RferSNMPu1 can be used as a potential target for the olfactory communication disruption in the R. ferrugineus control strategies.

Abstract Background The transition from childhood to adulthood, or adolescence, a developmental stage, is characterized by psychosocial and biological changes. The nucleus accumbens (NAc), a striatal brain region composed of the core (NAcC) and shell (NAcSh), has been linked to risk-taking behavior and implicated in reward seeking and evaluation. Most neurons in the NAc are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1R +) and/or dopamine D2 receptors (D2R +). Changes in dopaminergic and glutamatergic systems occur during adolescence and converge in the NAc. While there are previous investigations into sex differences in membrane excitability and synaptic glutamate transmission in both subdivisions of the NAc, to our knowledge, none have specified NAcSh D1R + MSNs from mice during pre- and mid-adolescence. Methods Sagittal brain slices containing the NAc were prepared from B6.Cg-Tg(Drd1a-tdTomato)6Calak/J mice of both sexes from postnatal days 21–25 and 35–47, representing pre- and mid-adolescence, respectively. Whole-cell electrophysiology recordings were collected from NAcSh D1R + MSNs in the form of membrane-voltage responses to current injections, to assess membrane properties and action potential waveform characteristics, and spontaneous excitatory postsynaptic currents (sEPSCs) to assess glutamatergic synaptic activity. Results Relative to pre-adolescent males, pre-adolescent female NAcSh D1R + MSNs exhibited a less hyperpolarized resting membrane potential, increased input resistance, and smaller action potential afterhyperpolarization amplitudes. During mid-adolescence, decreased input resistance and a shorter action potential duration in females were the only sex differences observed. Conclusions Taken together, our results indicate that NAcSh D1R + MSNs in mice exhibit sex differences in membrane properties and AP waveform during pre-adolescence that are overall indicative of increased cellular excitability in females and are suggestive of possible sex differences in glycine receptors, inwardly-rectifying potassium channels, and large conductance voltage-gated potassium channels. These differences do not appear to persist into mid-adolescence, when sex was observed to affect input resistance oppositely to that of pre-adolescence and AP waveform in a manner suggestive of differences in voltage-gated potassium channels.

Abstract Background Carpal tunnel syndrome (CTS) is the most common entrapment neuropathy with multifactorial etiologies. We intended in this case–control study to identify, out of a comprehensive set of risk factors, the relatively important ones and develop a quantitative risk assessment model for this disorder. It was also legitimate to define the hazard of those factors in a dose-related manner and the acceptable safe limit especially for work-related stresses. Results Age and female predominance were comparable between the 60 patients (89 hands with electrophysiologically confirmed CTS) and 50 controls (100 hands). Occupation of the studied sample varied between housewives only, employed housewives, and manual workers with a distribution that differed significantly between patients and controls. Significantly higher body mass index (BMI) and mean wrist depth were found in patients than controls. Wrist ratio (clinically or sonographically) was significantly squarer in patients than controls. Overall workload and number of hours spent daily performing work with repeated hand movements or awkward hand position were significantly higher among patients than controls. ROC curves were constructed for wrist measurements and occupational stresses. Cut-off points of wrist ratio and internal carpal tunnel ratio (by ultrasound) to discriminate subjects with CTS were > 0.68 and ≤ 1.854, respectively. The best cut-off value for number of hours spent daily performing work with repeated hand movements was 3 h/ day. As for working with awkward hand position or cold exposure, cut-off value was 0.6 h/day for both. Two logistic regression models were conducted to investigate nonoccupational and occupational predictors of CTS. The independent predictors concluded from the first model were BMI, positive family history of CTS, wrist ratio, and decrease grip strength. As for the occupational model, predictors were tasks requiring awkward hand position and cold exposure. Conclusion Occupational risk assessment by clinical, anthropometric, and ultrasonographic measurement should be used in professions requiring repetitive or awkward hand movements, so that in overweight persons with square wrists appropriate workplace setup measures or assistive technology at work or home could be taken to prevent or decrease the impact of work hazards or help choose individuals with low risk for appropriate jobs.

Abstract The flicker stimulus is a visual stimulus of intermittent illumination. A flicker stimulus can appear flickering or steady to a human subject, depending on the physical parameters associated with the stimulus. When the flickering light appears steady, flicker fusion is said to have occurred. This work aims to bridge the gap between the psychophysics of flicker fusion and the electrophysiology associated with flicker stimulus through a Deep Learning based computational model of flicker perception. Convolutional Recurrent Neural Networks (CRNNs) were trained with psychophysics data of flicker stimulus obtained from a human subject. We claim that many of the reported features of electrophysiology of the flicker stimulus, including the presence of fundamentals and harmonics of the stimulus, can be explained as the result of a temporal convolution operation on the flicker stimulus. We further show that the convolution layer output of a CRNN trained with psychophysics data is more responsive to specific frequencies as in human EEG response to flicker, and the convolution layer of a trained CRNN can give a nearly sinusoidal output for 10 hertz flicker stimulus as reported for some human subjects.

Background: Herpes zoster (HZ) is a viral disease characterized by skin eruptions and pain in specific dermatomes. Focal motor weakness that appears in the segment of skin eruptions is a rare complication of this infection. Because of the difficulty in clinically diagnosing thoracic or upper cervical motor weakness and due to the pain that causes overlooking of weakness, the true incidence of this complication is not known. In this study, we want to review the clinical presentation of segmental zoster paresis and also discuss electrophysiological findings with the involvement of nerve, plexus parts, or spinal roots. Methods: Electromyography records were examined retrospectively from 2010 to 2023 for patients who had HZ-associated limb paresis. Clinical data were reviewed and abstracted, and patients whose clinical limb weakness and sensory deficits conformed to the distribution of peripheral nerve (s) or spinal root and whose electrodiagnostic evaluation corroborated the localization, were included in the series. Results: Fifteen patients were included in our study. Ten of them were men and five of them were women. Paresis and neuropathic pain are the main complaints. In all patients, the distribution of paresis was consistent with the area of skin eruptions. C8–T1 in the upper extremity and L5–S1 in the lower extremity are the most commonly involved segments. Electrophysiological findings showed radicular involvement in three cases, brachial plexus in six cases, ulnar nerve in one case, sciatic nerve in two cases, and fibular nerve in three cases. Axonopathy is the main detected pathology in all cases. Conclusion: Segmental zoster paresis is a rare complication of cutaneous zona zoster and it affects different nerve segments. Clinicians should be aware of clinical and electrophysiological findings of this disease for the appropriate management of the patients.

Abstract In honey bees, circulation of blood (hemolymph) is driven by the peristaltic contraction of the heart vessel located in the dorsal part of the abdomen. Chlorantraniliprole (CHL) is an insecticide of the anthranilic diamide class which main mode of action is to alter the function of intracellular Ca2+ release channels (known as RyRs, for ryanodine receptors). In the honey bee, it was recently found to be more toxic when applied on the dorsal part of the abdomen, suggesting a direct cardiotoxicity. In the present study, a short-term exposure of semi-isolated bee hearts to CHL (0.1–10 µM) induces alterations of cardiac contraction. These alterations range from a slow-down of systole and diastole kinetics, to bradycardia and cardiac arrest. The bees heart wall is made of a single layer of semi-circular cardiomyocytes arranged concentrically all along the long axis of tube lumen. Since the heart tube is suspended to the cuticle through long tubular muscles fibers (so-called alary muscle cells), the CHL effects in ex-vivo heart preparations could result from the modulation of RyRs present in these skeletal muscle fibers as well as cardiomyocytes RyRs themselves. In order to specifically assess effects of CHL on cardiomyocytes, for the first time, intact heart cells were enzymatically dissociated from bees. Exposure of cardiomyocytes to CHL induces an increase in cytoplasmic calcium, cell contraction at the highest concentrations and depletion of intracellular stores. Electrophysiological properties of isolated cardiomyocytes were described, with a focus on voltage-gated Ca2+ channels responsible for the cardiac action potentials depolarization phase. Two types of Ca2+ currents were measured under voltage-clamp. Exposure to CHL was accompanied by a decrease in voltage-activated Ca2+ currents densities. Altogether, these results show that chlorantraniliprole can cause cardiac defects in honey bees.

Inflammatory bowel disease (IBD) is a clinical condition of the gastrointestinal tract that has significant incidence in childhood. Major symptoms include abdominal pain, dyspepsia, delayed gastric emptying, anorexia, diarrhea and weight loss. IBD etiopathogenesis is multifactorial, with a proven involvement of cytokines. In this regard, cytokines like resistin and adiponectin produced by adipose tissue play a crucial role in inflammation. Particularly, resistin seems related to IBD severity and is considered a promising marker of disease occurrence and progression. Unraveling its mechanism of action and downstream effectors is mandatory when designing novel therapies. This preclinical study aims to further elucidate the action of resistin in causing functional gastrointestinal alterations, comparing it with the well-defined effect of adiponectin. To this end, we carried out electrophysiological analysis on murine gastric fundus. We found that resistin, similarly to adiponectin, increases smooth muscle cell (SMC) capacitance, indicative of cell surface remodeling, which is consistent with relaxation. However, contrary to adiponectin, resistin unalters membrane potential and inward Ca2+ entry and scarcely affects outward current, suggesting its inefficacy in markedly modifying electrical phenomena on the SMC membrane. This outcome, supporting the role of resistin in gastrointestinal distention, as observed in IBD, rules out a strikingly direct effect on SMCs.

Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others. With one new patch clamp recording attempt, many new connections can be probed. By placing one pipette in front of the others in this way, one can ‘walk’ across the mouse brain slice, termed ‘patch-walking.’ We performed 136 patch clamp attempts for two pipettes, achieving 71 successful whole cell recordings (52.2%). Of these, we probed 29 pairs (i.e. 58 bidirectional probed connections) averaging 91 μm intersomatic distance, finding three connections. Patch-walking yields 80–92% more probed connections, for experiments with 10–100 cells than the traditional synaptic connection searching method.

It is widely acknowledged that microglia actively regulate synaptic function in the brain. Remarkably, much of our understanding regarding the role of microglia in synaptic regulation is derived from studies in acute brain slices. However, it is still uncertain to what extent the preparation and maintenance of acute slices can influence microglial function and whether microglial changes may affect synaptic transmission. In this study, we examined the impact of acute slice resting time on hippocampal CA1 microglia, by assessing morphological and functional parameters at two distinct time intervals. We report that after 4 h from slicing microglia undergo morphological, functional, and transcriptional changes, including a decrease in the number of branches and in their movement speed. Furthermore, microglia acquire a reactive phenotype, characterized by increased amplitude of outward rectifying K+ currents, increased expression of the pro-inflammatory cytokine Tnfα and altered expression of the microglial receptors Cx3cr1 and P2y12r. We also examined time-dependent changes of excitatory synaptic transmission in CA1 pyramidal neurons from acute hippocampal slices, reporting time-dependent decrease in both amplitude and frequency of postsynaptic currents (sEPSCs), along with a decrease in spine density. Noticeably, sEPSCs amplitude decrease was absent in slices prepared from PLX5622 microglia-depleted mice, suggesting that this time-dependent effect on synaptic transmission is microglia-dependent. Our findings highlight possible causal relation between microglia phenotypic changes in the hours following slice preparation and concomitant synaptic changes, pointing to the mechanisms of acute synaptic modulation, whose understanding is crucial for unraveling microglia-neurons interplay in nature. Furthermore, they emphasize the potential issues associated with experimental time windows in ex vivo samples.

IntroductionCoronary artery disease (CAD) is the foremost single cause of mortality and disability globally. Patients with type 2 diabetes (T2DM) have a higher incidence of CAD, and poorer prognosis. The low-grade inflammation associated to T2DM contributes to increased morbidity and worst outcomes after revascularization. Inflammatory signaling in the vasculature supports endothelial dysfunction, leukocyte infiltration, and macrophage activation to a metabolic disease (MMe) specific phenotype, which could contribute to the metabolic disorders and ascular damage in T2DM. We have previously found that Kv1.3 blockers inhibit the development of intimal hyperplasia, thereby preventing restenosis. This inhibition was enhanced in a mouse model of T2DM, where systemic Kv1.3 blockers administration also improve metabolic dysfunction by acting on unidentified cellular targets other than vascular smooth muscle. Here we characterize the MMe phenotype in our T2DM model with a focus on macrophage Kv1.3 channels, to explore their contribution to vascular disease and their potential role as targets to ameliorate T2DM vascular risk.Methods and ResultsMale and female BPH mice fed on high-fat diet (HFD) develop metabolic syndrome (MetS) and T2DM. mRNA levels of several K+ channels (KV1.3, KCa3.1, Kir2.1) and macrophage markers (TNFα, NOS2, CD36) were analyzed. The MMe phenotype associated with increased CD36 expression. Channel-specific fingerprinting highlights a gender-specific increase of KV1.3 mRNA fold change in LPS stimulated macrophages from HFD compared to standard diet (SD). KV1.3 functional expression was also significantly increased after LPS stimulation in female HFD macrophages compared to SD. Functional studies showed that macrophage's KV1.3 channels of BPH female mice did not contribute to phagocytosis or metabolic profile but were relevant in cell migration rate.ConclusionAltogether, our data suggest that by inhibiting macrophage infiltration, Kv1.3 blockers could contribute to disrupt the vicious cycle of inflammation and insulin resistance, offering a novel approach to prevent MetS, T2DM and its associated cardiovascular complications in females.

Abstract How consciousness is lost in states such as sleep or anesthesia remains a mystery. To gain insight into this phenomenon, concurrent recordings of electrophysiology signals in the anterior cingulate cortex and whole‐brain functional magnetic resonance imaging (fMRI) are conducted in rats exposed to graded propofol, undergoing the transition from consciousness to unconsciousness. The results reveal that upon the loss of consciousness (LOC), there is a sharp increase in low‐frequency power of the electrophysiological signal. Additionally, fMRI signals exhibit a cascade of deactivation across a pathway including the hippocampus, thalamus, and medial prefrontal cortex (mPFC) surrounding the moment of LOC, followed by a broader increase in brain activity across the cortex during sustained unconsciousness. Furthermore, sliding window analysis demonstrates a temporary increase in synchrony of fMRI signals across the hippocampus‐thalamus‐mPFC pathway preceding LOC. These data suggest that LOC may be triggered by sequential activities in the hippocampus, thalamus, and mPFC, while wide‐spread activity increases in other cortical regions commonly observed during anesthesia‐induced unconsciousness may be a consequence, rather than a cause of LOC. Taken together, the study identifies a cascade of neural events unfolding as the brain transitions into unconsciousness, offering insight into the systems‐level neural mechanisms underpinning LOC.

Kainate receptors are key modulators of synaptic transmission and plasticity in the central nervous system. Different kainate receptor isoforms with distinct spatiotemporal expressions have been identified in the brain. The GluK1-1 splice variant receptors, which are abundant in the adult brain, have an extra fifteen amino acids inserted in the amino-terminal domain (ATD) of the receptor resulting from alternative splicing of exon 9. However, the functional implications of this post-transcriptional modification are not yet clear. We employed a multi-pronged approach using cryogenic electron microscopy, electrophysiology, and other biophysical and biochemical tools to understand the structural and functional impact of this splice insert in the extracellular domain of GluK1 receptors. Our study reveals that the splice insert alters the key gating properties of GluK1 receptors and their modulation by the cognate auxiliary Neuropilin and tolloid-like (Neto) proteins 1 and 2. Mutational analysis identified the role of crucial splice residues that influence receptor properties and their modulation. Furthermore, the cryoEM structure of the variant shows that the presence of exon 9 in GluK1 does not affect the receptor architecture or domain arrangement in the desensitized state. Our study thus provides the first detailed structural and functional characterization of GluK1-1a receptors, highlighting the role of the splice insert in modulating receptor properties and their modulation.

Traditional methods for assessing vine water status, such as the Scholander pressure chamber, are time-consuming, punctual and labour-intensive. The development of alternative methods which are accurate, reliable and can provide real-time information on vine water status is a necessity for farmers all over the world. This study proposes the use of plant electrophysiology as a novel approach for real-time water status assessment in grapevines. We conducted four climate chamber experiments with potted grapevines under different irrigation regimes. Various morphological and physiological assessments were performed in parallel with electrophysiological measurements to correlate classic water status assessment methods with plant electrophysiological signals. Two machine learning approaches based on classification and regression were employed to train the prediction models. Results obtained from both models indicate significant differences in irrigation status between well-watered and water-deficit plants, with the latter showing reduced growth and physiological activity, confirming the water stress status of the plant. While the binary classification model successfully differentiates between well-watered and water-deficit plants, its practical use is limited. Therefore, a regression model was developed to directly predict predawn leaf water potential. To the best of our knowledge, this is the first time that electrical signals are correlated with vine water potential measurements. The findings presented here thus provide a promising new tool for future real-time and remote monitoring of vine water status to manage irrigation and adapt agronomic strategies. Nevertheless, validation and optimisation of the models are still necessary, particularly under field conditions.

IntroductionIn primary auditory cortex (A1), nicotinic acetylcholine receptors (nAChRs) containing α2 subunits are expressed in layer 5 Martinotti cells (MCs)—inhibitory interneurons that send a main axon to superficial layers to inhibit distal apical dendrites of pyramidal cells (PCs). MCs also contact interneurons in supragranular layers that, in turn, inhibit PCs. Thus, MCs may regulate PCs via inhibition and disinhibition, respectively, of distal and proximal apical dendrites. Auditory inputs to PCs include thalamocortical inputs to middle layers relaying information about characteristic frequency (CF) and near-CF stimuli, and intracortical long-distance (“horizontal”) projections to multiple layers carrying information about spectrally distant (“nonCF”) stimuli. CF and nonCF inputs integrate to create broad frequency receptive fields (RFs). Systemic administration of nicotine activates nAChRs to “sharpen” RFs—to increase gain within a narrowed RF—resulting in enhanced responses to CF stimuli and reduced responses to nonCF stimuli. While nicotinic mechanisms to increase gain have been identified, the mechanism underlying RF narrowing is unknown.MethodsHere, we examine the role of α2 nAChRs in mice with α2 nAChR-expressing neurons labeled fluorescently, and in mice with α2 nAChRs genetically deleted.ResultsThe distribution of fluorescent neurons in auditory cortex was consistent with previous studies demonstrating α2 nAChRs in layer 5 MCs, including nonpyramidal somata in layer 5 and dense processes in layer 1. We also observed label in subcortical auditory regions, including processes, but no somata, in the medial geniculate body, and both fibers and somata in the inferior colliculus. Using electrophysiological (current-source density) recordings in α2 nAChR knock-out mice, we found that systemic nicotine failed to enhance CF-evoked inputs to layer 4, suggesting a role for subcortical α2 nAChRs, and failed to reduce nonCF-evoked responses, suggesting that α2 nAChRs regulate horizontal projections to produce RF narrowing.DiscussionThe results support the hypothesis that α2 nAChRs function to simultaneously enhance RF gain and narrow RF breadth in A1. Notably, a similar neural circuit may recur throughout cortex and hippocampus, suggesting widespread conserved functions regulated by α2 nAChRs.

Cardiac screening of newly discovered drugs remains a longstanding challenge for the pharmaceutical industry. While therapeutic efficacy and cardiotoxicity are evaluated through preclinical biochemical and animal testing, 90 % of lead compounds fail to meet safety and efficacy benchmarks during human clinical trials. A preclinical model more representative of the human cardiac response is needed; heart tissue engineered from human pluripotent stem cell derived cardiomyocytes offers such a platform. In this study, three functionally distinct and independently validated engineered cardiac tissue assays are exposed to increasing concentrations of known compounds representing 5 classes of mechanistic action, creating a robust electrophysiology and contractility dataset. Combining results from six individual models, the resulting ensemble algorithm can classify the mechanistic action of unknown compounds with 86.2 % predictive accuracy. This outperforms single-assay models and offers a strategy to enhance future clinical trial success aligned with the recent FDA Modernization Act 2.0.

Abnormal accumulation of insoluble α-synuclein (α-Syn) inclusions in neurons, neurites, and glial cells is the defining neuropathology of synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy. Accumulation of α-Syn inclusions in the amygdala has been well-documented in post-mortem studies of PD and DLB brains, as well as preclinical animal models of these conditions. Though α-Syn pathology is closely associated with neurodegeneration, there is a poor correlation between neuronal loss in the amygdala and the clinical features of PD and DLB. Moreover, functional interaction between the cerebral cortex and the amygdala is critical to regulating emotion, motivation, and social behaviors. The cortico-amygdala functional interaction is likely to be disrupted by the development of α-Syn pathology in the brain. Thus, we hypothesize that neuronal α-Syn inclusions disrupt cortical modulation of the amygdala circuits and are sufficient to drive social behavioral deficits. In the present work, we designed a series of longitudinal studies to rigorously measure the time courses of neurodegeneration, functional impairment of cortico-amygdala connectivity, and development of amygdala-dependent social behavioral deficits to test this hypothesis. We injected α-Syn preformed fibrils (PFFs) into the dorsal striatum to induce α-Syn aggregation in the amygdala and the medial prefrontal cortex (mPFC) of C57BL6 mice of both sexes, followed by a detailed analysis of temporal development of α-Syn pathology, synaptic deficits, and neuronal loss in the amygdala, as well as behavioral deficits at 3–12 months post injections. Development of α-Syn inclusions caused losses of cortical axon terminals and cell death in the basolateral amygdala (BLA) at 6- and 12-months post injections, respectively. At a relatively early stage of 3 months post injections, the connection strength of the mPFC-BLA synapse was decreased in PFFs-injection mice compared to controls. Meanwhile, the PFFs-injected mice showed impaired social interaction behavior, which was rescued by chemogenetic stimulation of mPFC-BLA connections. Altogether, we presented a series of evidence to delineate circuit events in the amygdala associated with the accumulation of α-Syn inclusions in the mouse brain, highlighting that functional impairment of the amygdala is sufficient to cause social behavior deficits. The present work further suggests that early circuit modulation could be an effective approach to alleviate symptoms associated with α-Syn pathology, necessitating studies of functional consequences of α-Syn aggregation.

Abstract Background We aimed to identify different Guillain–Barré syndrome (GBS) subtypes, demyelination, axonal degeneration, and reversible conduction failure (RCF) as early as possible by analyzing the initial clinical and electrophysiological examinations. Methods This study retrospectively collected GBS patients between October 2018 and December 2022 at Beijing Tiantan Hospital. The diagnostic criteria for the initial electrophysiological study were based on Rajabally's criteria, and the criteria for the serial electrophysiological study were based on Uncini's criteria. All subjects underwent clinical and electrophysiological evaluations at least twice within 8 weeks. Results A total of 47 eligible patients with GBS were included, comprising 19 acute inflammatory demyelinating polyradiculoneuropathy (AIDP), 18 axonal degenerations, and 10 RCFs. In the RCF group, 40%, 30%, and 30% patients were diagnosed as AIDP, axonal, and equivocal at the initial study, respectively. The AIDP group had significantly higher cerebrospinal fluid (CSF) protein than the RCF (123.8 [106.4, 215.1] mg/dL vs. 67.1 [36.8, 85.6] mg/dL, p = 0.002) and axonal degeneration (123.8 [106.4, 215.1] mg/dL vs. 60.8 [34.8, 113.0] mg/dL, p

Dravet Syndrome (DS) is most often caused by heterozygous loss-of-function mutations in the voltage-gated sodium channel gene SCN1A (Nav1.1), resulting in severe epilepsy and neurodevelopmental impairment thought to be cause by reduced interneuron excitability. However, recent studies in mouse models suggest that interneuron dysfunction alone does not completely explain all the cellular and network impairments seen in DS. Here, we investigated the development of the intrinsic, synaptic, and network properties of CA1 pyramidal cells in a DS model prior to the appearance of overt seizures. We report that CA1 pyramidal cell development is altered by heterozygous reduction of Scn1a, and propose that this is explained by a period of reduced intrinsic excitability in early postnatal life, during which Scn1a is normally expressed in hippocampal pyramidal cells. We also use a novel ex vivo model of homeostatic plasticity to show an instability in homeostatic response during DS epileptogenesis. This study provides evidence for the early effects of Scn1a haploinsufficiency in pyramidal cells in contributing to the pathophysiology of DS.

IntroductionResurgent current (INaR) generated by voltage-gated sodium channels (VGSCs) plays an essential role in maintaining high-frequency firing of many neurons and contributes to disease pathophysiology such as epilepsy and painful disorders. Targeting INaR may present a highly promising strategy in the treatment of these diseases. Navβ4 and A-type fibroblast growth factor homologous factors (FHFs) have been identified as two classes of important INaR mediators; however, their receptor sites in VGSCs remain unknown, which hinders the development of novel agents to effectively target INaR.MethodsNavβ4 and FHF4A can mediate INaR generation through the amino acid segment located in their C-terminus and N-terminus, respectively. We mainly employed site-directed mutagenesis, chimera construction and whole-cell patch-clamp recording to explore the receptor sites of Navβ4 peptide and FHF4A in Nav1.7 and Nav1.8.ResultsWe show that the receptor of Navβ4-peptide involves four residues, N395, N945, F1737 and Y1744, in Nav1.7 DI-S6, DII-S6, and DIV-S6. We show that A-type FHFs generating INaR depends on the segment located at the very beginning, not at the distal end, of the FHF4 N-terminus domain. We show that the receptor site of A-type FHFs also resides in VGSC inner pore region. We further show that an asparagine at DIIS6, N891 in Nav1.8, is a major determinant of INaR generated by A-type FHFs in VGSCs.DiscussionCryo-EM structures reveal that the side chains of the critical residues project into the VGSC channel pore. Our findings provide additional evidence that Navβ4 peptide and A-type FHFs function as open-channel pore blockers and highlight channel inner pore region as a hotspot for development of novel agents targeting INaR.

Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as part of the Infant Brain Imaging Study (IBIS) Network and reports interim feasibility and data quality results. We evaluated feasibility by measuring the percentage of infants from whom we successfully collected each EEG paradigm. The quality of task-free data was assessed based on the duration of EEG recordings remaining after artifact removal. Preliminary analyses revealed low data loss, with average in-session loss rates at 4.16 % and quality control loss rates at 11.66 %. Overall, the task-free data retention rate, accounting for both in-session issues and quality control, was 84.16 %, with high consistency across sites. The insights gained from this preliminary analysis highlight key sources of data attrition and provide practical considerations to guide similar research endeavors.

Introduction The study of electrophysiological auditory measures with different types of masking makes it possible to understand temporal processing skills and the processes involved in speech recognition in noise situations. The use of modulated masking in cortical measures of hearing enables the obtainment of analysis parameters of the masking release and its impact on neural auditory processing.

Though animal models are still the gold standard for fundamental biological studies and drug evaluation for brain diseases, concerns arise from an apparent lack of reflecting the human genetics and pathophysiology. Recently, human avatars such as brain‐on‐a‐chip and brain organoids which are generated in a 3D manner using multiple types of human‐originated cells have risen as alternative testing models. Particularly in monitoring the functional neuronal cells that express action potentials in brain‐on‐a‐chip or brain organoids, various methods of measuring their electrophysiological function have been suggested for the study of brain‐related disease. Recent methodologies for analyzing the electrophysiology of different types of cells in brain‐on‐a‐chip and brain organoids are summarized in this review. We first emphasize the inherent features of brain‐on‐a‐chip and brain organoids from the perspective of the cell culture environment and accessibility to cells in the deep layer. The applicable monitoring techniques are then overviewed based on these features. Finally, we discuss the unmet needs for electrophysiology monitoring in advanced human brain avatar models.

Objective Cryoballoon ablation for pulmonary vein isolation is a time-efficient procedure that can alleviate stress on electrophysiology lab resources. This analysis modeled the impact of cryoballoon ablation on electrophysiology lab operation using data from Latin America. Methods Data from centers in Argentina, Mexico, Colombia, and Chile of the Cryo Global Registry were used as inputs for an electrophysiology lab efficiency simulation model. The model used the assumption that either two (today’s electrophysiology lab operations) or three (including electrophysiology lab operational changes) cryoballoon ablation procedures could be performed per day. The endpoints were the percentage of days that resulted in 1) overtime and 2) time left for an extra non-ablation electrophysiology procedure. Results Data from a total of 232 procedures from six Latin American centers were included in the analysis. The average electrophysiology lab occupancy time for all procedures in Latin America was 132 ± 62 minutes. In the Current Scenario (two procedures per day), 7.4% of simulated days resulted in overtime, and 81.4% had enough time for an extra electrophysiology procedure. In the Enhanced Productivity Scenario (three procedures per day), 16.4% of days used overtime, while 67.4% allowed time for an extra non-ablation electrophysiology procedure. Conclusions Using real-world, Latin American-specific data, we found that with operational changes, three ablation procedures could feasibly be performed daily, leaving time for an extra electrophysiology procedure on more than half of days. Thus, use of cryoballoon ablation is an effective tool to enhance electrophysiology lab efficiency in resource-constrained regions such as Latin America.

Abstract Bioelectronic medicine is emerging as a powerful approach for restoring lost endogenous functions and addressing life‐altering maladies such as cardiac disorders. Systems that incorporate both modulation of cellular function and recording capabilities can enhance the utility of these approaches and their customization to the needs of each patient. Here we report an integrated optogenetic and bioelectronic platform for stable and long‐term stimulation and monitoring of cardiomyocyte function in vitro. Optical inputs are achieved through the expression of a photoactivatable adenylyl cyclase, that when irradiated with blue light causes a dose‐dependent and time‐limited increase in the secondary messenger cyclic adenosine monophosphate with subsequent rise in autonomous cardiomyocyte beating rate. Bioelectronic readouts are obtained through a multi‐electrode array that measures real‐time electrophysiological responses at 32 spatially‐distinct locations. Irradiation at 27 µW mm−2 results in a 14% elevation of the beating rate within 20–25 min, which remains stable for at least 2 h. The beating rate can be cycled through “on” and “off” light states, and its magnitude is a monotonic function of irradiation intensity. The integrated platform can be extended to stretchable and flexible substrates, and can open new avenues in bioelectronic medicine, including closed‐loop systems for cardiac regulation and intervention, for example, in the context of arrythmias.

In the last few years, a plethora of biomarkers have been proposed for the differentiation of Parkinson’s disease (PD) from its mimics. Most of them consist of complex measures, often based on expensive technology, not easily employed outside research centers. MRI measures have been widely used to differentiate between PD and other parkinsonism. However, these measurements were often performed manually on small brain areas in small patient cohorts with intra- and inter-rater variability. The aim of the current review is to provide a comprehensive and updated overview of the literature on biomarkers commonly used to differentiate PD from its mimics (including parkinsonism and tremor syndromes), focusing on parameters derived by simple qualitative or quantitative measurements that can be used in routine practice. Several electrophysiological, sonographic and MRI biomarkers have shown promising results, including the blink-reflex recovery cycle, tremor analysis, sonographic or MRI assessment of substantia nigra, and several qualitative MRI signs or simple linear measures to be directly performed on MR images. The most significant issue is that most studies have been conducted on small patient cohorts from a single center, with limited reproducibility of the findings. Future studies should be carried out on larger international cohorts of patients to ensure generalizability. Moreover, research on simple biomarkers should seek measurements to differentiate patients with different diseases but similar clinical phenotypes, distinguish subtypes of the same disease, assess disease progression, and correlate biomarkers with pathological data. An even more important goal would be to predict the disease in the preclinical phase.

Background: Interest in cardiac electrophysiology is increasing in sub-Saharan Africa, but the interpretation of results is poorly understood. Cardiac electrophysiology is the study of electrical activity of the heart by virtue of catheters that are positioned in the heart, as opposed to leads placed on the chest surface. It is useful in identifying sites of origin of various cardiac arrhythmias, diagnosing conduction abnormalities and treating various arrhythmias. Material and method: This study is a review of cardiac electrophysiology methods. It aims to help physicians understand and interpret cardiac electrophysiology reports.

With the recent rise in the rate of alcohol use disorder (AUD) in women, the historical gap between men and women living with this condition is narrowing. While there are many commonalities in how men and women are impacted by AUD, an accumulating body of evidence is revealing sex-dependent adaptations that may require distinct therapeutic approaches. Preclinical rodent studies are beginning to shed light on sex differences in the effects of chronic alcohol exposure on synaptic activity in a number of brain regions. Prior studies from our laboratory revealed that, while withdrawal from chronic intermittent ethanol (CIE), a commonly used model of AUD, increased excitability in the ventral hippocampus (vHC) of male rats, this same treatment had the opposite effect in females. A follow-up study not only expanded on the synaptic mechanisms of these findings in male rats, but also established a CIE-dependent increase in the excitatory-inhibitory (E-I) balance of a glutamatergic projection from the basolateral amygdala to vHC (BLA-vHC). This pathway modulates anxiety-like behavior and could help explain the comorbid occurrence of anxiety disorders in individuals suffering from AUD. The present study sought to conduct a similar analysis of CIE effects on both synaptic mechanisms in the vHC and adaptations in the BLA-vHC pathway of female rats. Our findings indicate that CIE increases the strength of inhibitory neurotransmission in the vHC and that this sex-specific adaptation blocks, or at least delays, the increases in intrinsic vHC excitability and BLA-vHC synaptic transmission observed in males. Our findings establish the BLA-vHC pathway and the vHC as important circuitry to consider for future studies directed at identifying sex-dependent therapeutic approaches to AUD.

The infralimbic cortex (IL) is part of the medial prefrontal cortex (mPFC), exerting top-down control over structures that are critically involved in the development of alcohol use disorder (AUD). Activity of the IL is tightly controlled by γ-aminobutyric acid (GABA) transmission, which is susceptible to chronic alcohol exposure and withdrawal. This inhibitory control is regulated by various neuromodulators, including 5-hydroxytryptamine (5-HT; serotonin). We used chronic intermittent ethanol vapor inhalation exposure, a model of AUD, in male Sprague-Dawley rats to induce alcohol dependence (Dep) followed by protracted withdrawal (WD; 2 weeks) and performed ex vivo electrophysiology using whole-cell patch clamp to study GABAergic transmission in layer V of IL pyramidal neurons. We found that WD increased frequencies of spontaneous inhibitory postsynaptic currents (sIPSCs), whereas miniature IPSCs (mIPSCs; recorded in the presence of tetrodotoxin) were unaffected by either Dep or WD. The application of 5-HT (50 μM) increased sIPSC frequencies and amplitudes in naive and Dep rats but reduced sIPSC frequencies in WD rats. Additionally, 5-HT2A receptor antagonist M100907 and 5-HT2C receptor antagonist SB242084 reduced basal GABA release in all groups to a similar extent. The blockage of either 5-HT2A or 5-HT2C receptors in WD rats restored the impaired response to 5-HT, which then resembled responses in naive rats. Our findings expand our understanding of synaptic inhibition in the IL in AUD, indicating that antagonism of 5-HT2A and 5-HT2C receptors may restore GABAergic control over IL pyramidal neurons. Significance statement: Impairment in the serotonergic modulation of GABAergic inhibition in the medial prefrontal cortex contributes to alcohol use disorder (AUD). We used a well-established rat model of AUD and ex vivo whole-cell patch-clamp electrophysiology to characterize the serotonin modulation of GABAergic transmission in layer V infralimbic (IL) pyramidal neurons in ethanol-naive, ethanol-dependent (Dep), and ethanol-withdrawn (WD) male rats. We found increased basal inhibition following WD from chronic alcohol and altered serotonin modulation. Exogenous serotonin enhanced GABAergic transmission in naive and Dep rats but reduced it in WD rats. 5-HT2A and 5-HT2C receptor blockage in WD rats restored the typical serotonin-mediated enhancement of GABAergic inhibition. Our findings expand our understanding of synaptic inhibition in the infralimbic neurons in AUD.

The ventral pallidum (VP) has emerged as a critical node in the mesolimbic reward system. Modulating the VP can impact the subjective valuation of rewards, reward motivation, and reward seeking under conflict, making it an attractive target for clinical neuromodulation therapies that manage substance use disorders. To understand how to rationally modulate the VP, we need a better understanding of the electrophysiological properties of VP neurons and the molecular and biophysical determinants of these properties. Here, we used patch-clamp electrophysiology to characterize the intrinsic properties of glutamatergic VP (VPGlu) neurons and observed two distinct electrophysiological profiles: VPGlu neurons that undergo depolarization block in response to progressively increasing current injection amplitudes and those that were resistant to depolarization block. To explore the mechanisms that could contribute to these distinct profiles, we used targeted ribosome affinity purification to identify ion channel subunits and regulatory proteins by isolating actively transcribed mRNA selectively from VPGlu neurons. We then used this transcriptomic information to implement a Markov Chain Monte Carlo method to parameterize a large population of biophysically distinct multicompartment models of VPGlu neurons conforming to either subpopulation. Based on prior literature suggesting parvalbumin (PV) is expressed in a subset of VPGlu neurons, and that PV expression governs the firing properties of those neurons, we tested the hypothesis that PV expression accounted for differences in subgroups, by increasing the maximal firing frequency and conferring resistance to depolarization block. In contrast, our model determined that PV expression at physiological levels had no effect on maximum firing rate. However, supraphysiological expression levels of PV appeared to induce a depolarization block in previously depolarization block-resistant neuron models, suggesting that other intracellular calcium-binding proteins could play a role in determining the firing phenotype of VPGlu neurons. We corroborated this result with single-cell patch-clamp RT-PCR, which confirmed that PV expression did not distinguish the two electrophysiologically distinct subpopulations. Together, these findings establish that VPGlu neurons are composed of biophysically distinct subpopulations that have not been appreciated in prior studies interrogating the function of this population. With the advent of novel tools for cell-type specific pharmacology and targeted neurostimulation, this understanding will be critical for developing strategies to rationally modulate VPGlu cells to treat disorders characterized by maladaptive reward seeking.

Objective To explore the influencing factors affecting somatosensory evoked potential (SEP) during decompression laminectomy and to establish a prediction model. b>Methods The SEP monitoring data from 120 patients with spinal stenosis who underwent decompression laminectomy at the Spinal Orthopedics Department of Ma'anshan People's Hospital from January 2021 to January 2023 were analyzed retrospectively. Patients were divided into SEP-altered group (n=21) and control group (n=99) based on the presence or absence of SEP signal alteration. Predictors were determined using Lasso regression, cross-validation, logistic regression analysis. A column-line plot predicting change in SEP based on independent predictors was drawn. Receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves were used to evaluate the model. Results Logistic regression analysis indicated that overweight, hemorrhage, body temperature, and use of electrosurgical equipment were independent risk factors affecting SEP, with statistically significant differences (P＜0.05). In the validation of the model, the AUC of the column-line plot was 0.914, indicating that the model had good discrimination. The optimal calibration curve showed good agreement between predicted and actual values. The clinical decision curve attested to the practical efficacy of the model. Conclusion Factors affecting changes in SEP include overweight, hemorrhage, body temperature, and the use of electrosurgical equipment. The construction of a column chart to forecast SEP changes empowers spinal physicians to implement proactive therapeutic interventions effectively, concurrently enhancing the precision of electrophysiological monitoring.

Parkinson's disease (PD) is a neurodegeneration disease with α-synuclein accumulated in the substantia nigra pars compacta (SNpc) and most of the dopaminergic neurons are lost in SNpc while patients are diagnosed with PD. Exploring the pathology at an early stage contributes to the development of the disease-modifying strategy. Although the “gut–brain” hypothesis is proposed to explain the underlying mechanism, where the earlier lesioned site in the brain of gastric α-synuclein and how α-synuclein further spreads are not fully understood. Here we report that caudal raphe nuclei (CRN) are the early lesion site of gastric α-synuclein propagating through the spinal cord, while locus coeruleus (LC) and substantia nigra pars compacta (SNpc) were further affected over a time frame of 7 months. Pathological α-synuclein propagation via CRN leads to neuron loss and disordered neuron activity, accompanied by abnormal motor and non-motor behavior. Potential neuron circuits are observed among CRN, LC, and SNpc, which contribute to the venerability of dopaminergic neurons in SNpc. These results show that CRN is the key region for the gastric α-synuclein spread to the midbrain. Our study provides valuable details for the “gut–brain” hypothesis and proposes a valuable PD model for future research on early PD intervention.

Mounting interest in mental health conditions over the last two decades has been coupled with the increasing sophistication of techniques to study the brain in vivo.

Abstract The nasal potential difference test (nPD) is an electrophysiological measurement which is altered in patients and animal models with cystic fibrosis (CF). Because protocols and outcomes vary substantially between laboratories, there are concerns over its validity and precision. We performed a systematic literature review (SR) of the nPD to answer the following review questions: A. Is the nasal potential difference similarly affected in CF patients and animal models?”, and B. “Is the nPD in human patients and animal models of CF similarly affected by various changes in the experimental set-up?”. The review protocol was preregistered on PROSPERO (CRD42021236047). We searched PubMed and Embase with comprehensive search strings. Two independent reviewers screened all references for inclusion and extracted all data. Included were studies about CF which described in vivo nPD measurements in separate CF and control groups. Risk of bias was assessed, and three meta-analyses were performed. We included 130 references describing nPD values for CF and control subjects, which confirmed substantial variation in the experimental design and nPD outcome between groups. The meta-analyses showed a clear difference in baseline nPD values between CF and control subjects, both in animals and in humans. However, baseline nPD values were, on average, lower in animal than in human studies. Reporting of experimental details was poor for both animal and human studies, and urgently needs to improve to ensure reproducibility of experiments within and between species.

Abstract Background Bundle branch reentrant ventricular tachycardia is a unique type of VT that employs both bundles and the ventricular septum as integral components of a re-entrant circuit. It is usually observed in dilated cardiomyopathy, and its circuit depends exclusively on the specialized conduction system. Case presentation A 67-year-old man with a history of Fabry disease, and atrial fibrillation ablation, was admitted for a wide QRS tachycardia at 150 bpm, with an LBBB. Pharmacological therapy failed to stop the arrhythmia. Intracardiac recordings confirm the diagnosis. His Bundle recordings are essential, and Atrioventricular (AV) dissociation is typically present. The method used to induce left BBRVT is right ventricle apex stimulation. An electrophysiological study showed an AV dissociation a long HV sequence and a similar QRS morphology between VT and sinus rhythm. An overdrive stopped it. The same arrhythmia reappears and is restored to sinus rhythm by electrical cardioversion. We decided to implant an Implantable Cardiac defibrillator (ICD) with a backup pacing for secondary prevention and to ablate the right bundle branch. Conclusion BBRVT is a rare entity that is underreported. Pharmacological therapy is usually inefficient. An ICD is recommended for secondary prevention and can provide backup pacing, frequently required after catheter ablation to prevent the development of AV block or an excessive prolonged HV interval. Catheter ablation of the bundle branch is the first-line therapy.

This report discusses a case of transient 2:1 atrioventricular block with conduction system pacing 4 hours after leadless right ventricular pacemaker implantation in a 19-year-old patient with a history of cardioinhibitory syncope and asystole cardiac arrest but without preexisting atrioventricular block. The atrioventricular block was resolved spontaneously. Pacing morphology was suggestive of right bundle branch pacing. Neither 2:1 atrioventricular block nor conduction system pacing has previously been a reported outcome of right ventricular leadless pacemaker implantation. The report demonstrates that conduction system pacing with leadless devices is achievable. Further study of techniques, limitations, and complications related to intentional right ventricular leadless conduction system pacing is warranted.

A topical issue is the determination of the optimal values of activation time of local endograms (LE) and bipolar signal morphology during ablation in patients with idiopathic ventricular arrhythmias (VA) at the site of successful suppression, and the influence of 3D navigation on these values. The aim. To study earliest activation time (EAT) and LE morphology in the area of successful suppression during ablation of idiopathic VA using 3D navigation. Materials and methods. Analysis of the results of ablation in 57 patients with idiopathic VA was made. The patients were divided into two groups. Group I included 30 (52.6%) patients in whom mapping was performed using 3D navigation (EnSite Velocity Cardiac Mapping System). Group II included 27 (47.4%) patients who were mapped using conventional methods. In group I, extrasystole was found in 20 (66.7%) patients, while ventricular tachycardia was observed in 10 (33.3%) patients. In group II, extrasystole was revealed in 16 (59.3%) patients, and ventricular tachycardia in 11 (40.7%) patients. Group I included 21 (70%) patients with right ventricular localization of arrhythmia and 9 (30%) patients with left ventricular localization. Meanwhile, group II included 17 (63%) patients with a focus in the right ventricle and 10 (33%) patients with that in the left ventricle. The morphology of the LE was evaluated according to criteria such as polarity (positive or negative) and degree of signal fragmentation (monomorphic or fragmented). Polarity was determined by the initial direction of the signal during the first 10 ms, regardless of further changes in the endogram. The signal was considered fragmented if there were three or more polarity changes. Results. In group I, EAT of LE was -38.0±7.0 ms, while in group II it was -38.0±8.5 ms. No difference was found between the studied groups (p=0.834). Among all patients in both groups, the average value of EAT of LE at the site of successful arrhythmia elimination was -37.0±8.5 ms. In 92.9% cases EAT of LE was -30 ms or earlier. Only in four (7.1%) patients it was possible to achieve suppression of the arrhythmia with EAT of LE not earlier than -30 ms, while in all these cases the focus was always localized in the right ventricle. The minimum value of EAT of LE at the site of successful suppression of arrhythmia was -27 ms. The dominant morphology at the site of successful suppression among the patients in both groups, regardless of the type of mapping, was positive polarity of endogram. Conclusions. Regardless of the mapping method, in the site of successful idiopathic VA suppression LE must precede QRS by at least 27 ms.

Abstract The uterus exhibits intermittent electrophysiological activity in vivo. Although most active during labor, the non-pregnant uterus can exhibit activity of comparable magnitude to the early stages of labor. In this study, two types of flexible electrodes were utilized to measure the electrical activity of uterine smooth muscle in vivo in anesthetized, non-pregnant rats. Flexible printed circuit electrodes were placed on the serosal surface of the uterine horn of six anesthetized rats. Electrical activity was recorded for a duration of 20–30 min. Activity contained two components: high frequency activity (bursts) and an underlying low frequency ‘slow wave’ which occurred concurrently. These components had dominant frequencies of 6.82 ± 0.63 Hz for the burst frequency and 0.032 ± 0.0055 Hz for the slow wave frequency. There was a mean burst occurrence rate of 0.76 ± 0.23 bursts per minute and mean burst duration of 20.1 ± 6.5 s. The use of multiple high-resolution electrodes enabled 2D mapping of the initiation and propagation of activity along the uterine horn. This in vivo approach has the potential to provide the organ level detail to help interpret non-invasive body surface recordings.

Abstract Since antiquity human taste has been divided into 4–5 taste qualities. We realized in the early 1970s that taste qualities vary between species and that the sense of taste in species closer to humans such as primates should show a higher fidelity to human taste qualities than non-primates (Brouwer et al. in J Physiol 337:240, 1983). Here we present summary results of behavioral and single taste fiber recordings from the distant South American marmoset, through the Old World rhesus monkey to chimpanzee, the phylogenetically closest species to humans. Our data show that in these species taste is transmitted in labelled-lines to the CNS, so that when receptors on taste bud cells are stimulated, the cell sends action potentials through single taste nerve fibers to the CNS where they create taste, whose quality depends on the cortical area stimulated. In human, the taste qualites include, but are perhaps not limited to sweet, sour, salty, bitter and umami. Stimulation of cortical taste areas combined with inputs from internal organs, olfaction, vision, memory etc. leads to a choice to accept or reject intake of a compound. The labelled-line organization of taste is another example of Müller’s law of specific nerve energy, joining other somatic senses such as vision (Sperry in J Neurophysiol 8:15–28, 1945), olfaction (Ngai et al. in Cell 72:657–666, 1993), touch, temperature and pain to mention a few.

Particulate matter (PM) has always received widespread attention, PM2.5 pollution is associated with many adverse effects, including cardiovascular, respiratory and metabolic diseases and mood disorders. However, the underlying mechanisms are not yet clear. In this study, the small animal whole body inhalation exposure system collected real-time PM2.5 in the real environment, which can truly reflect the presence status of PM2.5 in the atmospheric environment. This study investigated the depressive like behavior of mice exposed to PM2.5 for a long time and proved its molecular mechanism through RNA-seq. C57BL/6 male mice were exposed to ambient air together with control mice, who breathed air filtered through high-efficiency air particulate filters. Depression like behavior was observed in mice exposed to PM for 4, 6, and 8 weeks through behavioral experiments, EEG signals, and pathological sections. RNA-seq results indicated that the depressive like behavior of mice exposed to PM2.5 might be related to pro-inflammatory and anti-inflammatory cytokines, as well as the BDNF pathways in the hippocampus and olfactory bulb. This study suggests that PM2.5 may induce depression in mice through the MAPK/CREB/BDNF pathway. Environmental Implication: Atmospheric particulate matter has been classified as Class 1 pollutant by the International Agency for Research on Cancer. Current research mainly believed that PM2.5 seriously affected lung health, but there was little research on the effects of PM2.5 on other organs. With the improvement of quality of life, people were paying more attention to mental health, while there is little research on the effects of PM2.5 on brain. This study simulated a real PM2.5 exposure environment and explored the effects of PM2.5 on the brain of mice, provided a solid scientific basis for inducing depression after PM2.5 exposure.

The endogenous endocannabinoid-like compound N-arachidonoyl-L-serine (ARA-S) facilitates activation of the human Kv7.1/KCNE1 channel and shortens a prolonged action potential duration and QT interval in guinea pig hearts. Hence, ARA-S is interesting to study further in cardiac models to explore the functional impact of such Kv7.1/KCNE1-mediated effects. To guide which animal models would be suitable for assessing ARA-S effects, and to aid interpretation of findings in different experimental models, it is useful to know whether Kv7.1/KCNE1 channels from relevant species respond similarly to ARA-S. To this end, we used the two-electrode voltage clamp technique to compare the effects of ARA-S on Kv7.1/KCNE1 channels from guinea pig, rabbit, and human Kv7.1/KCNE1, when expressed in Xenopus laevis oocytes. We found that the activation of Kv7.1/KCNE1 channels from all tested species was facilitated by ARA-S, seen as a concentration-dependent shift in the voltage-dependence of channel opening and increase in current amplitude and conductance over a broad voltage range. The rabbit channel displayed quantitatively similar effects as the human channel, whereas the guinea pig channel responded with more prominent increase in current amplitude and maximal conductance. This study suggests that rabbit and guinea pig models are both suitable for studying ARA-S effects mediated via Kv7.1/KCNE1.

The number of opioid overdose deaths has increased over the past several years, mainly driven by an increase in the availability of highly potent synthetic opioids, like fentanyl, in the un-regulated drug supply. Over the last few years, changes in the drug supply, and in particular the availability of counterfeit pills containing fentanyl, have made oral use of opioids a more common route of administration. Here, we used a drinking in the dark (DiD) paradigm to model oral fentanyl self-administration using increasing fentanyl concentrations in male and female mice over 5 weeks. Fentanyl consumption peaked in both female and male mice at the 30 µg/mL dose, with female mice consuming significantly more fentanyl than male mice. Mice consumed sufficient fentanyl such that withdrawal was precipitated with naloxone, with males having increased withdrawal symptoms as compared to females, despite lower pharmacological exposure. We also performed behavioral assays to measure avoidance behavior and reward-seeking during fentanyl abstinence. Female mice displayed reduced avoidance behaviors in the open field assay, whereas male mice showed increased avoidance in the light/dark box assay. Female mice also exhibited increased reward-seeking in the sucrose preference test. Fentanyl-consuming mice of both sexes showed impaired cued fear extinction learning following fear conditioning and increased excitatory synaptic drive and increased excitability of BLA principal neurons. Our experiments demonstrate that long-term oral fentanyl consumption results in wide-ranging physiological and behavioral disruptions. This model could be useful to further study fentanyl withdrawal syndrome and behaviors and neuroplasticity associated with protracted fentanyl withdrawal.

ABSTRACTL-type calcium channels (LTCCs), the major portal for Ca2+ entry into cardiomyocytes, are essential for excitation-contraction coupling and thus play a central role in regulating overall cardiac function. LTCC function is finely tuned by multiple signaling pathways and accessory proteins. Leucine-rich repeat-containing protein 10 (LRRC10) is a little studied cardiomyocyte-specific protein recently identified as a modulator of LTCCs. LRRC10 exerts a remarkable effect on LTCC function, more than doubling L-type Ca2+ current (ICa,L) amplitude in a heterologous expression system by altering the gating of the channels without changing their surface membrane expression. Genetic ablation of LRRC10 expression in mouse and zebrafish hearts leads to a significant reduction in ICa,L density and a slowly progressive dilated cardiomyopathy in mice. Rare sequence variants of LRRC10 have been identified in dilated cardiomyopathy and sudden unexplained nocturnal cardiac death syndrome, but these variants have not been clearly linked to disease. Nevertheless, the DCM-associated variant, I195T, converted LRRC10 from a ICa,L potentiator to a ICa,L suppressor, thus illustrating the wide dynamic range of LRRC10-mediated ICa,L regulation. This review focuses on the contemporary knowledge of LTCC modulation by LRRC10 and discusses potential directions for future investigations.