Recording of Age-Related Changes on Murine and Human Brain Slices.

Preparation of brain slices for electrophysiological and imaging experiments has been developed several decades ago, and the method is still widely used due to its simplicity and advantages over other techniques. It can be easily combined with other well established and recently developed methods as immunohistochemistry and morphological analysis or opto- and chemogenetics. Several aspects of this technique are covered by a plethora of excellent and detailed review papers, in which one can gain a deep insight of variations in it. In this chapter, I briefly describe the solutions, equipment, and preparation techniques routinely used in our laboratory. I also aim to present how certain "old school" brain slice lab devices can be made in a cost-efficient way. These devices can be easily adapted for the special needs of the experiments. I also aim to present some differences in the preparatory techniques of acutely isolated human brain tissue.

Rapid and local neuroestrogen synthesis supports long-term potentiation of hippocampal Schaffer collaterals-cornu ammonis 1 synapse in ovariectomized mice.

In aging women, cognitive decline and increased risk of dementia have been associated with the cessation of ovarian hormones production at menopause. In the brain, presence of the key enzyme aromatase required for the synthesis of 17-ß-estradiol (E2) allows for local production of E2 in absence of functional ovaries. Understanding how aromatase activity is regulated could help alleviate the cognitive symptoms. In female rodents, genetic or pharmacological reduction of aromatase activity over extended periods of time impair memory formation, decreases spine density, and hinders long-term potentiation (LTP) in the hippocampus. Conversely, increased excitatory neurotransmission resulting in rapid N-methyl-d-aspartic acid (NMDA) receptor activation rapidly promotes neuroestrogen synthesis. This rapid modulation of aromatase activity led us to address the hypothesis that acute neuroestrogens synthesis is necessary for LTP at the Schaffer collateral-cornu ammonis 1 (CA1) synapse in absence of circulating ovarian estrogens. To test this hypothesis, we did electrophysiological recordings of field excitatory postsynaptic potential (fEPSPs) in hippocampal slices obtained from ovariectomized mice. To assess the impact of neuroestrogens synthesis on LTP, we applied the specific aromatase inhibitor, letrozole, before the induction of LTP with a theta burst stimulation protocol. We found that blocking aromatase activity prevented LTP. Interestingly, exogenous E2 application, while blocking aromatase activity, was not sufficient to recover LTP in our model. Our results indicate the critical importance of rapid, activity-dependent local neuroestrogens synthesis, independent of circulating hormones for hippocampal synaptic plasticity in female rodents.

Common SYNE2 Genetic Variant Associated With Atrial Fibrillation Lowers Expression of Nesprin-2α1 With Downstream Effects on Nuclear and Electrophysiological Traits.

BACKGROUND: Atrial fibrillation GWAS (genome-wide association studies) identified significant associations for rs1152591 and linked variants in the SYNE2 gene encoding Nesprin-2, which connects the nuclear membrane with the cytoskeleton. METHODS: Reporter gene vector transfection and CRISPR-Cas9 editing were used to identify the causal variant regulating the expression of SYNE2α1. After SYNE2 knockdown or SYNE2α1 overexpression in human stem cell-derived cardiomyocytes, nuclear phenotypes were assessed by imaging and atomic force microscopy. Gene expression was assessed by RNAseq and gene set enrichment analysis. Fura-2 AM staining assessed calcium transients. Optical mapping assessed action potential duration and conduction velocity. RESULTS: The risk allele of rs1152591 had lower promoter and enhancer activity and was significantly associated with lower expression of the short SYNE2α1 isoform in human stem cell-derived cardiomyocytes, without an effect on the expression of the full-length SYNE2 mRNA. SYNE2α1 overexpression had dominant negative effects on the nucleus with its overexpression or SYNE2 knockdown leading to increased nuclear area and decreased nuclear stiffness. Gene expression results from SYNE2α1 overexpression demonstrated both concordant and nonconcordant effects with SYNE2 knockdown. SYNE2α1 overexpression had a gain of function on electrophysiology, leading to significantly faster calcium reuptake and decreased assessed action potential duration, while SYNE2 knockdown showed both shortened assessed action potential duration and decreased conduction velocity. CONCLUSIONS: rs1152591 was identified as a causal atrial fibrillation variant, with the risk allele decreasing SYNE2α1 expression. Downstream effects of SYNE2α1 overexpression include changes in nuclear stiffness and electrophysiology, which may contribute to the mechanism for the risk allele's association with AF.

Sex differences in glutamate transmission and plasticity in reward related regions.

Disruptions in glutamate homeostasis within the mesolimbic reward circuitry may play a role in the pathophysiology of various reward related disorders such as major depressive disorders, anxiety, and substance use disorders. Clear sex differences have emerged in the rates and symptom severity of these disorders which may result from differing underlying mechanisms of glutamatergic signaling. Indeed, preclinical models have begun to uncover baseline sex differences throughout the brain in glutamate transmission and synaptic plasticity. Glutamatergic synaptic strength can be assessed by looking at morphological features of glutamatergic neurons including spine size, spine density, and dendritic branching. Likewise, electrophysiology studies evaluate properties of glutamatergic neurons to provide information of their functional capacity. In combination with measures of glutamatergic transmission, synaptic plasticity can be evaluated using protocols that induce long-term potentiation or long-term depression. This review will consider preclinical rodent literature directly comparing glutamatergic transmission and plasticity in reward related regions of males and females. Additionally, we will suggest which regions are exhibiting evidence for sexually dimorphic mechanisms, convergent mechanisms, or no sex differences in glutamatergic transmission and plasticity and highlight gaps in the literature for future investigation.

Management of Rapid Atrial Fibrillation Using Stellate Ganglion Blockade.

Background: Stellate ganglion blockade has been demonstrated as an efficacious treatment for refractory ventricular tachyarrhythmias. There are no published reports of the use of this technique in management of rapid atrial arrhythmia. Case Summary: A 73-year-old woman presented to our institution in rapid atrial fibrillation and cardiogenic shock. She was intubated for airway protection and underwent successful electrical cardioversion. However, atrial fibrillation returned multiple times with weaning of sedation for extubation. Stellate ganglion infusion catheter was placed with infusion of ropivacaine and subsequent maintenance of sinus rhythm, with successful extubation, ablation of atrial fibrillation, improvement of left ventricular ejection fraction, and discharge. Take-Home Message: For selected patients, stellate ganglion blockade can be used as a technique to aid in the management of rapid atrial fibrillation.

When Is Mitral Regurgitation Not Just Systolic?: A Case of Near-Continuous Mitral Regurgitation.

A 30-year-old man presented with symptomatic severe chronic aortic regurgitation, first-degree atrioventricular block, and near-continuous mitral regurgitation. Surgical intervention, including aortic root replacement and mitral valve repair, was successful, highlighting the close relationship between valvular diseases and emphasizing the importance of comprehensive assessment for optimal management.

Prevalence and Predictors of Carpal Tunnel Syndrome Symptoms Among Teachers in Jazan: A Cross-Sectional Study.

Background  Carpal tunnel syndrome (CTS) is a common musculoskeletal condition of the hand and wrist frequently associated with repetitive hand motion and environmental considerations. Teachers are more likely to acquire CTS because of their lengthy writing and computer use. This study aimed to determine the prevalence of CTS symptoms and related variables among schoolteachers in Jazan, Saudi Arabia. Methods This study was conducted as a cross-sectional survey of teachers in Jazan, utilizing an online platform for data collection. The Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) was the primary tool used to determine symptom intensity and functional status. The data were rigorously analyzed using a range of statistical methods, including descriptive statistics, the Mann-Whitney U test, the Kruskal-Wallis test, Spearman's correlation, the chi-square test, Fisher's exact test, and binary logistic regression, ensuring the robustness of the findings. Results The study comprised 336 schoolteachers with a mean age of 43.3 ± 6.5 years, of whom 58.0% were female and 42.0% were male. About 8.0% of instructors reported CTS symptoms. Female gender (median Symptom Severity Scale (SSS): 15.0 vs. 12.0, p < 0.001; median Functional Status Scale (FSS): 8.0 vs. 8.0, p < 0.001), increased time spent writing (r = 0.237, p < 0.001 for SSS; r = 0.217, p < 0.001 for FSS), and presence of comorbidities such as diabetes (median SSS: 16.0, p = 0.002; median FSS: 8.0, p = 0.001) had a negative correlation with symptom severity (r = -0.174, p = 0.002) and functional impairment (r = -0.141, p = 0.011). Surgical therapy (median SSS: 32.0; median FSS: 24.0; p<0.001) and post-treatment symptom recurrence (median SSS: 28.0; median FSS: 22.0; p<0.001) were associated with increased severity and disability. According to binary logistic regression, increased writing time significantly predicted CTS diagnosis (OR = 1.151, 95% CI: 1.024-1.295, p = 0.018). Conclusion CTS symptoms are common among Jazan teachers, and various sociodemographic, vocational, and clinical variables influence their intensity and functional status. Ergonomic treatment, early identification, and suitable management measures are critical for preventing and mitigating the effects of CTS among teachers. Additional research is required to develop focused therapies and enhance the results of this occupational group.

Automated wave labelling of the auditory brainstem response using machine learning.

OBJECTIVE: To compare the performance of a selection of machine learning algorithms, trained to label peaks I, III, and V of the auditory brainstem response (ABR) waveform. An additional algorithm was trained to provide a confidence measure related to the ABR wave latency estimates. DESIGN: Secondary data analysis of a previously published ABR dataset. Five types of machine learning algorithm were compared within a nested k-fold cross-validation procedure. STUDY SAMPLE: A set of 482 suprathreshold ABR waveforms were used. These were recorded from 81 participants with audiometric thresholds within normal limits. RESULTS: A convolutional recurrent neural network (CRNN) outperformed the other algorithms evaluated. The algorithm labelled 95.9% of ABR waves within ±0.1 ms of the target. The mean absolute error was 0.025 ms, averaged across the outer validation folds of the nested cross-validation procedure. High confidence levels were generally associated with greater wave-labelling accuracy. CONCLUSIONS: Machine learning algorithms have the potential to assist clinicians with ABR interpretation. The present work identifies a promising machine learning approach, but any algorithm to be used in clinical practice would need to be trained on a large, accurately labelled, heterogeneous dataset and evaluated in clinical settings in follow-on work.

Mnemonically modulated perceptual processing to represent allocentric space in macaque inferotemporal cortex.

To encode allocentric space information of a viewing object, it is important to relate perceptual information in the first-person perspective to the representation of an entire scene which would be constructed before. A substantial number of studies investigated the constructed scene information (e.g., cognitive map). However, only few studies have focused on its influence on perceptual processing. Therefore, we designed a visually guided saccade task requiring monkeys to gaze at objects in different locations on different backgrounds clipped from large self-designed mosaic pictures (parental pictures). In each trial, we presented moving backgrounds prior to object presentations, indicating a frame position of the background image on a parental picture. We recorded single-unit activities from 377 neurons in the posterior inferotemporal (PIT) cortex of two macaques. Equivalent numbers of neurons showed space-related (119 of 377) and object-related (125 of 377) information. The space-related neurons coded the gaze locations and background images jointly rather than separately. These results suggest that PIT neurons represent a particular location within a particular background image. Interestingly, frame positions of background images on parental pictures modulated the space-related responses dependently on parental pictures. As the frame positions could be acquired by only preceding visual experiences, the present results may provide neuronal evidence of a mnemonic effect on current perception, which might represent allocentric object location in a scene beyond the current view.

Simple biomarkers to distinguish Parkinson's disease from its mimics in clinical practice: a comprehensive review and future directions.

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.

Unusual Recurrent Multivessel Coronary Artery Spasm: A Case Report and Literature Review.

Coronary artery spasms (CAS) can manifest in various forms, from silent ischemia to severe cardiac events like myocardial infarction and sudden death. This case involves a 56-year-old male with recurrent ischemic chest pain and varying ECG signs. Cardiac catheterization revealed multiple coronary spasms that resolved spontaneously or with intracoronary nitroglycerin. The report emphasizes the severe presentations of multiple CAS and the importance of thorough diagnostic evaluation to avoid unnecessary interventions, highlighting the diagnostic challenges in managing such cases.

Pallidal neuronal activity in Gilles de la Tourette syndrome and dystonic patients: A comparative study.

Gilles de la Tourette syndrome (GTS) and dystonia (DYS) are both hyperkinetic movement disorders effectively treated by deep brain stimulation (DBS) of the internal part of the globus pallidus (GPi). In this study, we compared single-neuron activity in the GPi between 18 GTS patients (with an average of 41 cells per patient) and 17 DYS patients (with an average of 54 cells per patient), all of whom underwent bilateral pallidal stimulation surgery, under general anesthesia or while awake at rest. We found no significant differences in GPi neuronal activity characteristics between patients operated on under general anesthesia versus those who were awake, irrespective of their diagnosis (GTS or DYS). We found higher firing rates, firing rate in bursts, pause duration and interspike interval coefficient of variation in GTS patients compared to DYS patients. On the opposite, we found higher number of pauses and bursts frequency in DYS patients. Lastly, we found a higher proportion of GPi oscillatory activities in DYS compared to GTS patients, with predominant activity within the low-frequency band (theta/alpha) in both patient groups. These findings underscore the complex relationship between the different neuronal discharge characteristic such as oscillatory or bursting activity within the GPi in shaping the clinical phenotypes of hyperkinetic disorders. Further research is warranted to deepen our understanding of how neuronal patterns are transmitted within deep brain structures and to develop strategies aimed at normalizing these pathological activities, by refining DBS techniques to enhance treatment efficacy and individual outcomes.

Exposure to nicotine and withdrawal in Wistar rats: an electrophysiological study.

INTRODUCTION: Throughout the world, smoking is one of the principal causes of preventable death. Nicotine, the primary active component of tabacco, acts as a psychostimulant and modulates the electrical activity of a number of the areas of the brain involved in addiction. Abstinence from nicotine will also impact the functional state of the brain, which is reflected in symptoms of craving and susceptibility to relapse. In addition, given the increase in the sympathetic tone of the heart and pulse rate promoted by nicotine, its consumption can contribute to tachyarrhythmia. METHODS: The present study investigated the electroencephalographic (EEG) and electrocardiographic (ECG) patterns of Wistar rats submitted to acute or chronic exposure to nicotine, followed by withdrawal for 24 or 48 hours, and the re-administration (or not) of nicotine, to simulate episodes of relapse. RESULTS: The EEG data revealed an increase in all types of brainwaves, with emphasis on high-frequency (alpha, beta, and gamma) brain oscillations following both acute and chronic exposure to nicotine (14 days), whereas in withdrawal, there was a predominancy of delta waves. When exposure to nicotine was reinstated after withdrawal, the observed EEG profile was similar to that found in chronic exposure. The electrocardiogram reads showed that both acute and chronic exposure to nicotine caused abnormalities in the atrioventricular conduction and that, while these changes improve with substance withdrawal, relapse can worsen these parameters. CONCLUSIONS: The results of this study indicate that high-frequency brainwaves are correlated with nicotine dependence, while slow brain oscillations are consistent with drug craving, and episodes of nicotine relapse can reproduce brain activity patterns linked to dependence. Finally, exposure to nicotine predisposes the individual to heart rhythm abnormalities, which are attenuated by withdrawal, but may nevertheless be restored rapidly with re-exposure to the substance. IMPLICATIONS: This study demonstrated that nicotine increases high-frequency brain oscillations, which is associated with addiction, whereas withdrawal elevates the delta wave power, suggesting craving. Re-exposure to nicotine following withdrawal restores rapidly the EEG profile of chronic dependence. In addition, nicotine has deleterious impacts on cardiac activity, which are linked to fatal arrhythmias. This implies that stopping smoking is beneficial for the amelioration of the alterations in heart rhythm caused by nicotine addiction. This study elucidates the functional states of the brain and heart during both sporadic and chronic nicotine use, and the electrophysiological explanation for substance dependence and drug relapse after craving episodes.

Localization of neurons from extracellular footprints.

BACKGROUND: High density microelectrode arrays (HD-MEAs) are now widely used for both in-vitro and in-vivo recordings, as they allow spikes from hundreds of neurons to be recorded simultaneously. Since extracellular recordings do not allow visualization of the recorded neurons, algorithms are needed to estimate their physical positions, especially to track their movements when the are drifting away from recording devices. NEW METHOD: The objective of this study was to evaluate the performance of multiple algorithms for neuron localization solely from extracellular traces (MEA recordings), either artificial or obtained from mouse retina. The algorithms compared included center-of-mass, monopolar, and grid-based algorithms. The first method is a barycenter calculation. The second algorithm infers the position of the cell using triangulation with the assumption that the neuron behaves as a monopole. Finally, grid-based methods rely on comparing the recorded spike with a projection of spikes of hypothetical neurons with different positions. RESULTS: The Grid-Based algorithm yielded the most satisfactory outcomes. The center-of-mass exhibited a minimal computational cost, yet its average localization was suboptimal. Monopolar algorithms gave cell localizations with an average error of less than 10µm, but they had considerable variability and a high computational cost. For the grid-based method, the variability was smaller, with satisfactory performance and low computational cost. COMPARISON WITH EXISTING METHOD(S): The accuracy of the different localization methods benchmarked in this article had not been properly tested with ground-truth recordings before. CONCLUSION: The objective of this article is to provide guidance to researchers on the selection of optimal methods for localizing neurons based on MEA recordings.

Functional specialization and distributed processing across marmoset lateral prefrontal subregions.

A prominent aspect of primate lateral prefrontal cortex organization is its division into several cytoarchitecturally distinct subregions. Neurophysiological investigations in macaques have provided evidence for the functional specialization of these subregions, but an understanding of the relative representational topography of sensory, social, and cognitive processes within them remains elusive. One explanatory factor is that evidence for functional specialization has been compiled largely from a patchwork of findings across studies, in many animals, and with considerable variation in stimulus sets and tasks. Here, we addressed this by leveraging the common marmoset (Callithrix jacchus) to carry out large-scale neurophysiological mapping of the lateral prefrontal cortex using high-density microelectrode arrays, and a diverse suite of test stimuli including faces, marmoset calls, and spatial working memory task. Task-modulated units and units responsive to visual and auditory stimuli were distributed throughout the lateral prefrontal cortex, while those with saccade-related activity or face-selective responses were restricted to 8aV, 8aD, 10, 46 V, and 47. Neurons with contralateral visual receptive fields were limited to areas 8aV and 8aD. These data reveal a mixed pattern of functional specialization in the lateral prefrontal cortex, in which responses to some stimuli and tasks are distributed broadly across lateral prefrontal cortex subregions, while others are more limited in their representation.

Adolescent alcohol consumption predicted by differences in electrophysiological functional connectivity and neuroanatomy.

Alcohol consumption during adolescence has been associated with neuroanatomical abnormalities and the appearance of future disorders. However, the latest advances in this field point to the existence of risk profiles which may lead to some individuals into an early consumption. To date, some studies have established predictive models of consumption based on sociodemographic, behavioral, and anatomical-functional variables using MRI. However, the neuroimaging variables employed are usually restricted to local and hemodynamic phenomena. Given the potential of connectome approaches, and the high temporal dynamics of electrophysiology, we decided to explore the relationship between future alcohol consumption and electrophysiological connectivity measured by MEG in a cohort of 83 individuals aged 14 to 16. As a result, we found a positive correlation between alcohol consumption and the functional connectivity in frontal, parietal, and frontoparietal connections. Once this relationship was described, multivariate linear regression analyses were used to evaluate the predictive capacity of functional connectivity in conjunction with other neuroanatomical and behavioral variables described in the literature. Finally, the multivariate linear regression analysis determined the importance of anatomical and functional variables in the prediction of alcohol consumption but failed to find associations with impulsivity, sensation seeking, and executive function scales. In conclusion, the predictive traits obtained in these models were closely associated with changes occurring during adolescence, suggesting the existence of different paths in neurodevelopment that have the potential to influence adolescents' relationship with alcohol consumption.

Unveiling the mystery of the female heart's rhythm: a look into gender inequalities in electrophysiology.

This review explores gender disparities in cardiac electrophysiology, highlighting differences in the electrical activity of the heart between men and women. It emphasizes the importance of understanding these variances for correct diagnosis and effective treatment of cardiac arrhythmias. Women show distinct cardiac characteristics influenced by sex hormones, affecting their susceptibility to various arrhythmias. The manuscript covers the classification, mechanisms, and management of arrhythmias in women, considering factors such as pregnancy and menopause. By addressing these gender-specific nuances, it aims to improve healthcare practices and outcomes for female patients with cardiac rhythm disorders.

Esta revisión explora las disparidades de género en la electrofisiología cardiaca, destacando las diferencias en la actividad eléctrica del corazón entre hombres y mujeres. Se enfatiza la importancia de comprender estas variaciones para un diagnóstico correcto y un tratamiento efectivo de las arritmias cardiacas. Las mujeres muestran características cardiacas distintas influenciadas por las hormonas sexuales, lo que afecta su susceptibilidad a diversas arritmias. La revisión abarca la clasificación, los mecanismos y el manejo de las arritmias en las mujeres, considerando factores como el embarazo y la menopausia. Al abordar estos matices específicos de género, el objetivo es mejorar las prácticas de atención médica y los resultados para las pacientes de sexo femenino con trastornos del ritmo cardiaco.