Search Results (275)

Research on filial imprinting has yielded insights into a range of behavioural and neurobiological phenomena, and these insights have in turn fed back to elucidate behavioural development. This review will summarize important stages in this progression, with emphasis on the neural mechanisms underlying visual filial imprinting in the domestic chick. Imprinting entails recognition of stimuli, in terms of both form and certain abstract features. A striking property of imprinting is the development of a preference for a stimulus slightly different from one that has become familiar, a property having profound implications for survival. Compelling evidence indicates that the intermediate and medial mesopallium (IMM) in the chick forebrain is a site of memory encoding for imprinting. In addition, processes within the IMM are intimately associated with learning capacity in the absence of specific experience (a predisposition). Electrophysiological, neuroanatomical, pharmacological, biochemical and ablation studies have implicated the IMM in the recognition of individual conspecifics, and recent research has elucidated the underlying neurobiological mechanisms at the cellular and sub-cellular levels. Results from studies of imprinting in chicks have led to the discovery of analogous processes in humans and promise to yield insights into cognitive development in both species. Full article

Background: Strength-Duration (S-D) assessment is commonly used in clinics to examine the excitability of peripheral nerves and muscles. Yet, how changes in neuromuscular excitability relate to improved athletic and muscular performance in healthy subjects remains poorly understood. Therefore, the aim of the study was to evaluate the electrophysiological changes in neuromuscular excitability in the vastus medialis (VM) muscle using the S-D assessment, following a back squat conditioning activity (BS-CA) protocol designed to elicit a post-activation potentiation (PAP)/post-activation performance enhancement (PAPE) effect in healthy athletic males. Methods: Eleven male physical education students were included in this study. All subjects performed two trials: one examining their BS one-repetition maximum (1-RM), and a main experiment. During the main experiment, baseline levels of rectangular rheobase (R-RIC), triangular rheobase (R-DIC), and chronaxie were collected from the VM muscle following a standard warmup. Subsequently, the subjects performed four warmup BS sets and executed a top set of five repetitions (reps) at 80% of 1-RM. Afterwards, R-RIC, R-DIC, and chronaxie were reassessed for pre and post analysis. Based on these S-D curve (SDC) parameters, the muscle adjustability quotient (MAQ) and threshold charge (Q) were also computed and compared. Results: The R-RIC, R-DIC and Q were all significantly higher following the BS-CA, compared to pre-intervention (p < 0.001). No significant differences were observed for the chronaxie and MAQ (p > 0.05), although an increasing trend was noted for the chronaxie (p = 0.054). Conclusions: Based on the findings from this study, the neuromuscular excitability in the VM muscle can be acutely altered following a BS-CA protocol. However, these changes seem to be more related to muscle fatigue than PAP/PAPE. Nevertheless, S-D assessment may broaden our understanding of the fatigue process during exercise. Full article

In this paper, we present a multi-parallel restricted additive Schwarz (MP-RAS) preconditioner construction method for cardiac electrophysiology simulation. This method is designed to address the need for solving large-scale linear systems in realistic cardiac electrophysiology simulations and can provide a more efficient computational tool for patient-specific electrical propagation modeling, arrhythmia studies, and the evaluation of ablation strategies. The proposed preconditioner is suitable for the finite element simulation of the anisotropic cardiac monodomain model. In particular, we construct the subdomains based on Morton code sorting, build submatrices by indices and decompose the formula for parallel computing. Given that the computing of each subdomain is relatively independent, the iteration can be extended to N-parallel. Numerical experiments indicate that for matrices of the same size and under the same number of partitions, Morton code sorting is at least 105 times faster than METIS, while the memory usages are reduced by 12∼32%. The iteration number is reduced by approximately two times compared with the Jacobi and block Jacobi preconditioned conjugate gradient (PCG) method. Comparative experiments with other solvers further demonstrate that the MP-RAS solver is highly efficient for solving this parabolic partial differential equation and have strong parallel scalability. Full article

Serotonergic projections innervate both the dorsal and ventral cochlear nuclei; however, the electrophysiological consequences of serotonergic input in the ventral cochlear nucleus (VCN) remain incompletely understood. This study aimed to identify the serotonin receptor subtypes involved in serotonergic modulation of stellate cells in the mouse anteroventral cochlear nucleus (AVCN) and to determine the underlying ion channel mechanisms. Whole-cell patch-clamp recordings were performed in acute brain slices obtained from postnatal day 12–17 mice. Bath application of serotonin (25 µM) induced membrane depolarization (~5 mV) and increased action potential firing. Pharmacological experiments demonstrated that antagonists of 5-HT1A, 5-HT2A, and 5-HT2C receptors partially reversed the depolarization and reduced serotonin-induced inward currents, indicating that multiple receptor subtypes contribute to serotonergic excitation. Blockade of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels with extracellular Cs⁺ suppressed approximately 95% of the serotonin-induced depolarization and inward current, implicating HCN channel-mediated Ih as a principal ionic mechanism. Serotonin significantly increased Ih amplitude. Analysis of steady-state activation revealed no statistically significant shift in V0.5; however, under near-resting membrane potential conditions, serotonin significantly reduced the slope factor of the activation curve, consistent with altered voltage sensitivity of Ih gating. Immunohistochemical analysis confirmed the presence of 5-HT1A, 5-HT2A, and 5-HT2C receptors in the AVCN. Together, these findings indicate that serotonergic excitation of AVCN stellate cells is mediated by coordinated activation of multiple 5-HT receptor subtypes and primarily involves modulation of HCN-dependent subthreshold membrane dynamics. Full article

Background: Athletes may experience paroxysmal arrhythmias that occur during exercise and are difficult to document using standard diagnostic modalities. Such arrhythmias are often unpredictable, transient, and cannot be reproduced during routine exercise testing or ambulatory electrocardiographic monitoring, leading to prolonged diagnostic pathways and uncertainty regarding management. Methods: This case series presents ten athletes in whom clinically relevant paroxysmal arrhythmias were initially detected using commercially available wearable digital devices, primarily chest-strap heart rate monitors and smartwatches. Results: In most cases, arrhythmias could not be documented using conventional diagnostic methods despite repeated investigations. Most presented athletes were referred for invasive electrophysiological study, which confirmed supraventricular arrhythmias and enabled curative catheter ablation based solely on data obtained from wearable devices. The use of digital devices substantially shortened the time to diagnosis and treatment, reduced diagnostic burden, and allowed definitive therapy in symptomatic athletes. Conclusions: Wearable technology, particularly chest-strap heart rate monitors, may play an important role in the diagnostic evaluation of exercise-induced paroxysmal arrhythmias when standard methods fail. Full article

Background: Neuropsychiatric disorders such as Alzheimer’s disease (AD), bipolar disorder (BD), and depression exhibit shared glutamatergic abnormalities, although their upstream molecular mechanisms remain poorly defined. Magnesium (Mg²⁺) serves as a key regulator of N-methyl-D-aspartate (NMDA) receptor function; however, the role of Mg²⁺ transporters, particularly SLC41A1, has not been systematically investigated. As NMDA receptor dysregulation contributes to emotional and cognitive impairments, elucidating Mg²⁺-NMDA signaling may enable the development of novel therapeutic strategies. Methods: We integrated Mendelian randomization, locus colocalization, human brain transcriptomics, functional enrichment, and co-expression analyses to determine whether SLC41A1 functions as a cross-disorder molecular driver. In addition, in vitro electrophysiological experiments using field potential recordings in hippocampal Schaffer-CA1 synapses were conducted to validate its functional role in NMDA receptor-mediated synaptic transmission. Results: Genetically elevated SLC41A1 expression increased the risk of AD, BD, depression, and alcohol dependence, with strong colocalization analyses supporting shared causal variants. Transcriptomic profiling revealed SLC41A1 upregulation in AD and BD, with enrichment in magnesium transport, mitochondrial function, and synaptic signaling pathways. Co-expression networks across GTEx brain regions demonstrated strong correlations with NMDA-related genes (e.g., GRINA, CAMK2G, GRIN2C). Under NMDAR-selective recording conditions, both imipramine treatment and SLC41A1 knockdown significantly reduced NMDAR-mediated fEPSP amplitudes, supporting a role for SLC41A1 in regulating NMDA receptor-dependent synaptic responses. Conclusions: This study identifies SLC41A1 as a magnesium-centered, transdiagnostic therapeutic target that links Mg²⁺ homeostasis to NMDA-dependent synaptic dysfunction. These findings provide a mechanistic foundation for developing SLC41A1-modulating or magnesium-based therapeutic approaches for mood and cognitive disorders. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no disease-modifying therapy that halts or substantially slows disease progression is currently available. Although antibody therapies targeting amyloid β (Aβ) have recently received FDA approval, their high cost, limited efficacy, and potential adverse effects highlight the need for alternative solutions. Therefore, the development of low-molecular-weight compounds capable of reducing toxic Aβ aggregates is of considerable interest. In this study, we investigated the effects of 2,3,4-trihydroxybenzophenone (THB) on the inhibition and disassembly of Aβ_1–42 aggregates through in vitro and in vivo experiments. Methods: In vitro assays were performed to evaluate the effects of THB on Aβ_1–42 aggregation and fibril disassembly. Cell viability assays and hippocampal slice electrophysiology were conducted to assess neurotoxicity and synaptic function. In vivo effects were examined in Aβ_1–42 aggregate-injected mice and in 5 Familial AD mutations (5XFAD) mice using behavioral, histological, and electrophysiological analyses. Results: THB inhibited Aβ_1–42 aggregation in a concentration-dependent manner and promoted the disassembly of preformed fibrils. THB attenuated Aβ_1–42-induced Neuro2a cell death and restored Aβ_1–42 aggregate-associated long-term potentiation (LTP) deficits in hippocampal slices. In Aβ_1–42 aggregate-injected and 5XFAD mice, THB reduced amyloid pathology and neuroinflammatory markers and improved synaptic function and memory performance. Conclusions: These findings suggest that THB modulates pathogenic Aβ_1–42 assemblies and provides a structural basis for the development of small-molecule modulators of Aβ_1–42 aggregation with potential preventive or disease-modifying applications in AD. Full article

High-resolution, multi-modal neural interfaces are essential for advancing systems neuroscience and brain–computer interface technologies. This study designed and fabricated a 128-channel comb-shaped flexible micro-electrode array. The device integrates a biocompatible Parylene substrate with a flexible thin-film microprobe array, enabling simultaneous recording of electrocorticography (ECoG), intracortical local field potentials (LFP), and neuronal action potentials (spikes) from the cortical surface and superficial layers. Microelectrode sites were modified with platinum black nanoparticles, significantly reducing impedance. In vivo experiments in rats demonstrated the array’s ability to capture high-fidelity signals across different recording depths. Key findings included the acquisition of opposing LFP trends and polarity reversals between adjacent channels, reflecting local microcircuit dynamics. The array also reliably recorded neural activity during audiovisual cross-modal sensory stimulation. These results validate the device as an effective tool for multi-scale electrophysiology, successfully balancing high spatial resolution and signal quality with minimal tissue invasiveness, thereby offering significant potential for fundamental research and neural engineering applications. Full article

Voltage-gated potassium channel Kv1.3 plays an important role in the regulation of survival and apoptosis in many cell types, including both normal and cancer cells. Inhibitors of these channels may potentially find clinical applications in the treatment of various diseases, including certain cancers characterized by the over-expression of Kv1.3. In this study, the effects of isobavachalcone (IBC) and two non-prenylated chalcones—2′-hydroxy-4,3′-dimethoxychalcone (HDC) and 2′-hydroxy-2-methoxychalcone (HMC)—on Kv1.3 channel activity were investigated in the Jurkat T cancer cell line using the whole-cell patch-clamp technique. The electrophysiological measurements were preceded by experiments assessing cell viability, and the patch-clamp data were consistent with results obtained from MTT-based assays. We observed an almost complete and irreversible inhibition of Kv1.3 in the presence of IBC. The non-prenylated chalcones also inhibited the channels, but with lower potency and in a reversible and incomplete manner. The inhibitory effect of IBC was significantly enhanced upon co-application with simvastatin (SIM) and mevastatin (MEV). In contrast, inhibition by the non-prenylated chalcones was significantly increased only in the presence of mevastatin, but not simvastatin. The channel inhibition may be related to the anti-proliferative and pro-apoptotic activities of these compounds in Kv1.3-expressing cancer cells. Altogether, our results indicate that both prenylated and non-prenylated chalcones, particularly in combination with statins, may represent biologically active scaffolds, warranting further optimization and preclinical evaluation. Full article

Oxidative stress-induced lipid peroxidation products (LPPs), particularly 4-hydroxy-nonenal (4-HNE) and 4-oxo-nonenal (4-ONE), have recently gained attention for their direct regulation of ion channels essential for pain signaling. In this study, we investigated how these two LPPs affect the electrophysiological properties of neurons, specifically voltage-gated sodium (Na_V) channels, thereby influencing sensory neuron excitability and pain pathways. Using human neuroblastoma (SH-SY5Y) and ND7/23 cells (a fusion cell line exhibiting partial sensory neuron properties), we measured changes in Na_V channel-mediated sodium currents following treatment with 4-HNE or 4-ONE. Whole-cell patch-clamp experiments showed that 4-ONE (10 µM) and 4-HNE (100 µM) did not significantly alter the peak sodium current amplitude in SH-SY5Y cells. However, in ND7/23 cells, both 4-HNE and 4-ONE induced a negative shift in Na_V channel activation voltage dependence, enabling sodium channel activation at lower membrane potentials. Furthermore, current-clamp recordings in primary mouse dorsal root ganglion neurons demonstrated that treatment with 4-ONE and 4-HNE reduced the current threshold required to elicit action potentials and significantly increased action potential firing frequency. These findings indicate that LPPs enhance pain sensitivity by modulating Na_V channels, which play a crucial role in pain transmission. In conclusion, 4-HNE and 4-ONE shift the voltage-dependent activation of sodium channels toward more negative potentials, thereby increasing the excitability of primary sensory neurons and amplifying pain signals. This study provides molecular insights into how oxidative stress-related lipid peroxidation contributes to sensory mechanisms and offers potential avenues for developing new treatments for oxidative stress- or inflammation-associated pain. Full article

Central nervous system (CNS) disorders such as depression severely impair human health. Targeted inhibition of the GluN1-GluN2A receptor is a promising therapeutic strategy, but current drugs often have adverse effects. To develop novel candidate drugs, this study utilized the (S)-ketamine and GluN1-GluN2A receptor complex as a structural template and conducted de novo drug design with the DrugFlow platform. An integrated strategy of molecular docking-based virtual screening combined with high-throughput binding free energy (∆G_binding) calculations from large-scale molecular dynamics (MD) simulations identified three promising antagonists. The ∆G_binding values of these compounds are all below −18.98 kcal/mol, indicating stronger binding affinity than (S)-ketamine, and they demonstrate promising drug-like properties and development potential. 200-ns MD simulations confirmed their stable receptor binding and mechanism consistent with (S)-ketamine. Electrophysiological recordings revealed that, at a concentration of 10 μM, Compounds A1, A2, and A3 produced concentration-dependent inhibition of GluN1-GluN2A receptor-mediated currents, with fractional inhibition values of 24.26%, 35.36%, and 41.76%, respectively. These findings demonstrate the compounds’ potential as CNS disorder therapeutics, requiring further experiments to validate efficacy and advance development for conditions like depression. Full article

Background: Complex neurodevelopmental disorders frequently reflect multiple neurologic symptoms which have shared molecular and network level mechanisms. Advances in genomic medicine have redefined these conditions as overlapping manifestations of brain circuit dysfunction with significant variability. This review examines the intersection of genomics, epilepsy, and neurodevelopment in complex neurodevelopmental disorders, emphasizing Dup15q syndrome as a model for understanding phenotypic variability. Methods: Authors conducted a clinical (non-systematic) review of the literature based on their experience with three patients with Dup15q who responded dramatically to neurostimulation. We synthesized current literature on genomic mechanisms underlying complex neurodevelopmental disorders focusing on Dup15q syndrome and its subtypes—int15, idic15, and mosaic idic15. We integrated clinical, electrophysiologic, and molecular data to illustrate the spectrum of epilepsy phenotypes and their mechanistic underpinnings. Results: Dup15q syndrome demonstrates marked heterogeneity in epilepsy severity and seizure semiology, reflecting variable gene dosing effects, maternal imprinting of UBE3A, and altered GABAergic signaling. While idic15 is more strongly associated with refractory epilepsy and SUDEP, both idic15 and int15 subtypes show overlapping developmental and behavioral phenotypes. There is a well-known differential response to anti-seizure medications and emerging evidence for neurostimulation and precision medicine. Conclusion: Dup15q syndrome exemplifies the convergence of genomic, neurophysiologic, and developmental pathways in epilepsy. As genomic discovery expands, precision therapies will increasingly rely on collaborative research networks. Understanding the genomic architecture of Dup15q syndrome may inform personalized strategies for epilepsy treatment and prevention. Full article

The patch-clamp technique is widely regarded as the gold standard in cellular electrophysiology and can be applied in several configurations. In the cell-attached (C-A) mode, it enables the recording of single-channel currents, whereas the whole-cell (W-C) mode allows for the measurement of macroscopic currents, representing the collective activity of many channels. When the recording configuration was switched from C-A to W-C on the same cell, the current amplitude increased dramatically, while action currents (ACs) were completely abolished, indicating a profound alteration in the cell’s electrophysiological response under the new setup. In excitable cells, the occurrence of ACs, representing propagated action potentials, can interfere with C-A single-channel recordings. To address this, a high-K⁺ solution is typically applied to the bath to suppress the ACs. The inwardly rectifying K⁺ (Kir), ATP-sensitive K⁺ (K_ATP) and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels are crucial members of the K⁺ channel family that facilitate the efflux of K⁺ ions, driven by the K⁺ electrochemical gradient. These channels are primarily distinguished by their rectification properties and gating kinetics. For instance, K_ATP channels exhibit a bursting kinetic pattern with inward rectifying property, while BK_Ca channels display strong outward rectification. Mitoxantrone, which belongs to a class of drugs called anthracenediones, can suppress the activity of Kir channels in differentiated RAW 264.7 cells, with no change in single-channel conductance. The respiratory stimulator GAL-021 acts as a BK_Ca channel inhibitor, and it suppresses channel activity and shifts the activation curve to the right, suggesting a voltage-dependent blockade that stabilizes the channel in a closed state. GAL-021 does not change the single-channel conductance, indicating it is a gating modifier rather than an open-pore blocker. The functional roles of ion channels are fundamentally important. Correspondingly, the field is transitioning to artificial intelligence for automated single-cell patch-clamp experiments, though brain slice recordings still require manual techniques. Full article

The integration of complementary metal–oxide–semiconductor (CMOS) and micro-electromechanical systems (MEMSs) technologies for miniaturized biosensor fabrication enables unprecedented spatiotemporal resolution in monitoring the bioelectrical activity of the nervous system. Wafer-level CMOS technology incurs high costs, but multi-project wafer (MPW) runs mitigate this by allowing multiple users to share a single wafer. Still, monolithic CMOS biosensors require specialized surface materials or device geometries incompatible with standard CMOS processes. Performing MEMS post-processing on the few square millimeters available in MPW dies remains a significant challenge. In this paper, we present a MEMS post-processing workflow tailored for CMOS dies that supports both surface material modification and layout shaping for intracortical biosensing applications. To address lithographic limitations on small substrates, we optimized spray-coating photolithography methods that suppress edge effects and enable reliable patterning and lift-off of diverse materials. We fabricated a needle-like, 512-channel simultaneous neural recording active pixel sensor (SiNAPS) technology based neural probe designed for integration with optical fibers for optogenetic studies. To mitigate photoelectric effects induced by light stimulation, we incorporated a photoelectric shield through simple modifications to the photolithography mask. Optical bench testing demonstrated >96% light-shielding effectiveness at 3 mW of light power applied directly to the probe electrodes. In vivo experiments confirmed the probe’s capability for high-resolution electrophysiological measurements. Full article

Total hip arthroplasty (THA) is a widely performed procedure that significantly enhances patients’ quality of life. However, nerve injury remains a concerning complication, with an incidence ranging from 0.6% to 3.7%, depending on patient and surgical variables. This narrative review provides a comprehensive overview of nerve injuries associated with THA, focusing on etiology, risk factors, clinical manifestations, prevention, and treatment strategies. The most affected nerves include the sciatic, femoral, lateral femoral cutaneous (LFCN), superior gluteal, and obturator nerves. Anatomical factors such as developmental hip dysplasia (DDH), limb length discrepancy, and aberrant nerve courses, along with patient-specific conditions like female sex, obesity, and pre-existing spinal disorders, increase the risk of nerve damage. Surgical complexity, revision procedures, and surgeon experience also influence injury likelihood. Clinical manifestations range from sensory disturbances to motor deficits including foot drop, Trendelenburg gait, or impaired knee extension, depending on the nerve involved. Diagnosis is primarily clinical, supported by electrophysiological studies and imaging when needed. Prevention hinges on careful preoperative planning, appropriate surgical approach selection, meticulous intraoperative technique, and attention to limb positioning. Treatment is typically conservative, involving pain control, physical therapy, and neurostimulation. In refractory or severe cases, interventions such as nerve decompression, repair, or tendon transfer may be considered. Pharmacological agents including vitamin B12, tacrolimus, and melatonin show potential in promoting nerve regeneration. Although most nerve injuries resolve spontaneously or with conservative measures, some cases may result in long-term deficits. Understanding the mechanisms, risk factors, and management strategies is essential to mitigating complications and optimizing functional outcomes in patients undergoing THA. Full article